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12,400 | 26,266,907 | Major elective surgery overcame many of these method ological limitations . | Background The design of clinical immunology studies in sepsis presents several fundamental challenges to improving the translational underst and ing of pathologic mechanisms .
We undertook a systematic review of bed-to-benchside studies to test the hypothesis that variable clinical design method ologies used to investigate immunologic function in sepsis contribute to apparently conflicting laboratory data , and identify potential alternatives that overcome various obstacles to improve experimental design . | The mechanisms of correcting immune disorders in patients with pancreatic cancer requiring major surgery procedures by introducing perioperative immune-enhancing diet ( immunonutrition ) are still unclear . The purpose of our study was to investigate the effect of pancreatic cancer , extensive surgery and immunonutrition versus enteral st and ard nutrition on the apoptotic signaling pathways . The r and omized studies were performed in 72 patients before and after pancreatic cancer resection with preoperative st and ard ( Group I ) or enteral immunonutrition ( Group II ) . The expressions of Bcl-2 , Bax , caspases-3 , -9 , NF-κB , PARP-1/89 kDa , TNFR1/CD120a and Fas/CD95 in peripheral blood lymphocytes were assessed by western blot analysis and flow cytometry before and on day 1 , 3 and 7 after surgery . In malnourished patients before and after surgery , the expression of Bcl-2 , Bax , NF-κB , PARP-1 was significantly lower , whereas the expression of caspases , as well as the percentage of cells with death receptors were significantly higher when compared with the control group . There was no difference in Bcl-2 , Bax and PARP-1 expression between the control group and the patients with normal nutritional status ( Group III ) before surgery . In comparison to the st and ard nutrition , the preoperative immunonutrition increased the Bcl-2 and Bax expression inconsiderably but significantly increased the percentage of CD95- and CD120a-positive lymphocytes after surgery . In malnourished patients with pancreatic cancer , the overwhelming expression of caspases and the decrease expression of anti-apoptotic proteins may lead to inappropriate lymphocyte apoptosis and higher cell depletion . The preoperative enteral immunonutrition prevents the postoperative decrease in lymphocyte subsets , but a higher level of lymphocyte susceptibility to undergo accelerated apoptosis can also be considered Introduction Septic shock remains a major health care problem worldwide . Sepsis-induced immune alterations are thought to play a major role in patients ' mortality and susceptibility to nosocomial infections . Programmed death-1 ( PD-1 ) receptor system constitutes a newly described immunoregulatory pathway that negatively controls immune responses . It has recently been shown that PD-1 knock-out mice exhibited a lower mortality in response to experimental sepsis . The objective of the present study was to investigate PD-1-related molecule expressions in septic shock patients . Methods This prospect i ve and observational study included 64 septic shock patients , 13 trauma patients and 49 healthy individuals . PD-1-related-molecule expressions were measured by flow cytometry on circulating leukocytes . Plasmatic interleukin (IL)-10 concentration as well as ex vivo mitogen-induced lymphocyte proliferation were assessed . Results We observed that septic shock patients displayed increased PD-1 , PD-Lig and 1 ( PD-L1 ) and PD-L2 monocyte expressions and enhanced PD-1 and PD-L1 CD4 + T lymphocyte expressions at day 1 - 2 and 3 - 5 after the onset of shock in comparison with patients with trauma and healthy volunteers . Importantly , increased expressions were associated with increased occurrence of secondary nosocomial infections and mortality after septic shock as well as with decreased mitogen-induced lymphocyte proliferation and increased circulating IL-10 concentration . Conclusions These findings indicate that PD-1-related molecules may constitute a novel immunoregulatory system involved in sepsis-induced immune alterations . Results should be confirmed in a larger cohort of patients . This may offer innovative therapeutic perspectives on the treatment of this hitherto deadly disease The objective of this study was to refine the APACHE ( Acute Physiology , Age , Chronic Health Evaluation ) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults . We prospect ively collected data on 17,440 unselected adult medical/surgical intensive care unit ( ICU ) admissions at 40 US hospitals ( 14 volunteer tertiary-care institutions and 26 hospitals r and omly chosen to represent intensive care services nationwide ) . We analyzed the relationship between the patient 's likelihood of surviving to hospital discharge and the following predictive variables : major medical and surgical disease categories , acute physiologic abnormalities , age , preexisting functional limitations , major comorbidities , and treatment location immediately prior to ICU admission . The APACHE III prognostic system consists of two options : ( 1 ) an APACHE III score , which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups ; and ( 2 ) an APACHE III predictive equation , which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients . A five-point increase in APACHE III score ( range , 0 to 299 ) is independently associated with a statistically significant increase in the relative risk of hospital death ( odds ratio , 1.10 to 1.78 ) within each of 78 major medical and surgical disease categories . The overall predictive accuracy of the first-day APACHE III equation was such that , within 24 h of ICU admission , 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed ( r2 = 0.41 ; receiver operating characteristic = 0.90 ) . Recording changes in the APACHE III score on each subsequent day of ICU therapy provided daily up date s in these risk estimates . When applied across the individual ICUs , the first-day APACHE III equation accounted for the majority of variation in observed death rates ( r2 = 0.90 , p less than 0.0001 ) Introduction Studies on the role of programmed death-1(PD-1 ) and its main lig and ( PD-L1 ) during experimental models of sepsis have shown that the PD-1/PD-L1 pathway plays a pathologic role in altering microbial clearance , the innate inflammatory response and accelerated apoptosis in sepsis . However , the expression of PD-1 and PD-L1 and their role during the development of immune suppression in septic patients have not been eluci date d. The present study was design ed to determine whether the expression of PD-1 and PD-L1 is upregulated in septic shock patients and to explore the role of this pathway in sepsis-induced immunosuppression . Methods Nineteen septic shock patients and 22 sex-matched and age-matched healthy controls were prospect ively enrolled . Apoptosis in lymphocyte sub population s and PD-1/PD-L1 expression on peripheral T cells , B cells and monocytes were measured using flow cytometry . Apoptosis of T cells induced by TNFα or T-cell receptor ligation in vitro and effects of anti-PD-L1 antibody administration were measured by flow cytometry . CD14 + monocytes of septic shock patients were purified and incubated with either lipopolysaccharide , anti-PD-L1 antibody , isotype antibody , or a combination of lipopolysaccharide and anti-PD-L1 antibody or isotype antibody . Supernatants were harvested to examine production of cytokines by ELISA . Results Compared with healthy controls , septic shock induced a marked increase in apoptosis as detected by the annexin-V binding and active caspase-3 on CD4 + T cells , CD8 + T cells and CD19 + B cells . Expression of PD-1 on T cells and of PD-L1 on monocytes was dramatically upregulated in septic shock patients . PD-1/PD-L1 pathway blockade in vitro with anti-PD-L1 antibody decreased apoptosis of T cells induced by TNFα or T-cell receptor ligation . Meanwhile , this blockade potentiated the lipopolysaccharide-induced TNFα and IL-6 production and decreased IL-10 production by monocytes in vitro . Conclusions The expression of PD-1 on T cells and PD-L1 on monocytes was upregulated in septic shock patients . The PD-1/PD-L1 pathway might play an essential role in sepsis-induced immunosuppression Patients with sepsis have impaired host defenses that contribute to the lethality of the disorder . Recent work implicates lymphocyte apoptosis as a potential factor in the immunosuppression of sepsis . If lymphocyte apoptosis is an important mechanism , specific subsets of lymphocytes may be more vulnerable . A prospect i ve study of lymphocyte cell typing and apoptosis was conducted in spleens from 27 patients with sepsis and 25 patients with trauma . Spleens from 16 critically ill nonseptic ( 3 prospect i ve and 13 retrospective ) patients were also evaluated . Immunohistochemical staining showed a caspase-9-mediated profound progressive loss of B and CD4 T helper cells in sepsis . Interestingly , sepsis did not decrease CD8 T or NK cells . Although there was no overall effect on lymphocytes from critically ill nonseptic patients ( considered as a group ) , certain individual patients did exhibit significant loss of B and CD4 T cells . The loss of B and CD4 T cells in sepsis is especially significant because it occurs during life-threatening infection , a state in which massive lymphocyte clonal expansion should exist . Mitochondria-dependent lymphocyte apoptosis may contribute to the immunosuppression in sepsis by decreasing the number of immune effector cells . Similar loss of lymphocytes may be occurring in critically ill patients with other disorders Introduction Although major changes of the immune system have been described in sepsis , it has never been studied whether these may differ in relation to the type of underlying infection or not . This was studied for the first time . Methods The statuses of the innate and adaptive immune systems were prospect ively compared in 505 patients . Whole blood was sample d within less than 24 hours of advent of sepsis ; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer . Results Expression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis . The rate of apoptosis of natural killer ( NK ) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia ( VAP ) and hospital-acquired pneumonia ( HAP ) compared with sepsis . The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis , primary bacteremia and VAP/HAP compared with sepsis . Regarding adaptive immunity , absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia ( CAP ) and intraabdominal infections compared with sepsis . Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis . Conclusions Major differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection . These results may have a major impact on therapeutics Introduction The impact of gender on outcome in critically ill patients is unclear . Weinvestigated the influence of gender on the epidemiology of severe sepsis and associated morbidity and mortality in a large cohort of ICU patients in the regionof Piedmont in Italy . Methods This was a post-hoc analysis of data from a prospect i ve , multicenter , observational study in which all patients admitted to one of 24 participatingmedical and /or surgical ICUs between 3 April 2006 and 29 September 2006 wereincluded . Results Of the 3,902 patients included in the study , 63.5 % were male . Female patients weresignificantly older than male patients ( 66 ± 16 years vs. 63 ± 16 years , P < 0.001 ) . Female patients were less likely to have severe sepsis and septic shock on admission to the ICU and to develop these syndromes during theICU stay . ICU mortality was similar in men and women in the whole cohort ( 20.1%vs . 19.8 % , P = 0.834 ) , but in patients with severe sepsis wassignificantly greater in women than in men ( 63.5 % vs. 46.4 % , P = 0.007).In multivariate logistic regression analysis with ICU outcome as the dependentvariable , female gender was independently associated with a higher risk of ICUdeath in patients with severe sepsis ( odds ratio = 2.33 , 95 % confidence interval = 1.23 to 4.39 , P = 0.009 ) but not in the whole cohort ( odds ratio = 1.07,95 % confidence interval = 0.87 to 1.34 ) . Conclusion In this large regional Italian cohort of ICU patients , there were more male thanfemale admissions . The prevalence of severe sepsis was lower in women than in men , but female gender was independently associated with a higher risk of death in theICU for patients with severe sepsis Although salutary effects of female sex steroids have been demonstrated not only in proestrus females but also in male animals treated with estradiol in different models of trauma , it remains unknown whether sex hormones influence post-traumatic immune response in humans . We therefore investigated the effect of sex and age on organ dysfunction and clinical course in patients with multiple injuries . Polytraumatized patients ( injury severity score > 16 ) between 16 and 65 years old admitted to the Hannover Medical School Level 1 trauma center between January 1997 and December 2001 were included . Marshall Score for multiple organ dysfunction syndrome ( MODS ) was calculated for at least 14 days . The length of stay in intensive care unit and the ventilator days were recorded in addition to the number of transfusions the patient received . A total of 106 males and 37 females were included in the study . Patients with MODS had increased plasma levels of IL-6 , IL-8 , and IL-10 . Furthermore , patients with organ dysfunction had more frequent sepsis and higher mortality rates . In addition , MODS was associated with extended length of stay in the intensive care unit and increased ventilator days . Females not older than 50 years with an injury severity score greater than 25 suffered significantly less MODS and sepsis compared with age-matched males . Moreover , they had significantly lower plasma cytokines . Thus , in this prospect i ve study , sex difference was confirmed in MODS and sepsis , with a benefit observed in females . Although the levels of sex steroids were not measured , it seems that the protective effects may be due to estrogen effects on plasma cytokines . This suggestion is based on the fact that such salutary effects were apparent predominantly in premenopausal females BACKGROUND Severe trauma may induce alternations of cytokine response and polymorphonuclear cell ( PMN ) activity in patients . This study investigated the correlation of plasma migration inhibitory factor ( MIF ) level and PMN activation after severe injury , and their relationship with clinical outcomes . STUDY DESIGN A prospect i ve observational study was performed at the emergency department and intensive care unit of a university hospital . Thirty-two severe blunt trauma patients ( Injury Severity Score greater than 16 ) with systemic inflammatory response syndrome ( SIRS ) were enrolled . Age- and gender-matched healthy persons were the controls . Patient blood sample s were obtained within 24 hours of and at 72 hours after injury . PMNs were isolated and measured for NF-kBp65 translocation and respiratory burst . Plasma MIF , tumor necrosis factor (TNF)-alpha , interleukin (IL)-6 , IL-8 , and IL-10 concentrations were measured . Control PMNs were incubated with patient plasma preincubated with anti-MIF antibody or anti-IL-6 antibody ; cytokine blockade effects were evaluated . RESULTS Twelve patients developed organ failure . Compared with patients without organ failure , patients with organ failure had lower blood pressure and a higher base deficit on admission , higher NF-kBp65 translocation and respiratory burst of PMNs , and higher plasma MIF ( 968 ± 246 pg/mL vs 564 ± 299 pg/mL ) and IL-6 ( 202 ± 91 pg/mL vs 119 ± 84 pg/mL ) levels within 24 hours after injury . Plasma MIF had significant positive correlation with NF-kB translocation of PMNs within 24 hours of incurring trauma ( R = 0.668 ) . The presence of anti-MIF antibody in patients ' plasma obtained within 24 hours , but not at 72 hours , after injury could significantly partially block the NF-kBp65 translocation and respiratory activity of PMNs in the controls . CONCLUSIONS An early increase of plasma MIF associates with NF-kB translocation and respiratory burst in PMNs of severe trauma patients and correlates with higher morbidity . MIF is one of the important factors responsible for early PMN activation and may provide a target of immunomodulation after injury Objective Primary events such as severe injury and elective surgery cause a deterioration of the immune response measurable by reduction of expression of HLA-DR on monocytes or ex vivo LPS-induced TNFα production . The further influence of secondary surgery after severe injury on the immune response remains unresolved . Design Prospect i ve observation study . Setting Surgical intensive care unit of an university hospital . Patients Sixteen severely injured patients with an ISS > 25 points . Measurements and results On day 1 after trauma and immediately before secondary surgery , mean fluorescence intensity ( MFI ) of HLA-DR expression on monocytes and TNFα ex vivo synthesis was significantly reduced compared to healthy donors . Overall , surgical intervention during the second week after trauma caused no further reduction of HLA-DR expression on monocytes and of the ex vivo TNFα- synthesis . However , major surgery such as intramedullary nailing or pelvic osteo synthesis caused reduction of the HLA-DR expression and TNFα- synthesis , whereas , minor surgical interventions such as osteo synthesis on peripheral joints exhibited no significant effects on the immune response . Surgical intervention performed to clear septic foci normalised immune response by elevating HLA-DR expression on monocytes and ex vivo TNFα synthesis . Severe injury caused elevated serum IL-10 levels , whereas secondary surgery did not induce a further increase in serum IL-10 levels . Conclusion This study shows that initial trauma as well as major secondary surgery causes a suppression of immune functions , whereas minor secondary surgery does not cause significant immune disturbance Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes Introduction In transgenic animal models of sepsis , members of the Bcl-2 family of proteins regulate lymphocyte apoptosis and survival of sepsis . This study investigates the gene regulation of pro-apoptotic and anti-apoptotic members of the Bcl-2 family of proteins in patients with early stage severe sepsis . Methods In this prospect i ve case-control study , patients were recruited from three intensive care units ( ICUs ) in a university hospital . Sixteen patients were enrolled when they fulfilled the criteria of severe sepsis . Ten critically ill but non-septic patients and 11 healthy volunteers served as controls . Blood sample s were immediately obtained at inclusion . To confirm the presence of accelerated apoptosis in the patient groups , caspase-3 activation and phosphatidylserine externalisation in CD4 + , CD8 + and CD19 + lymphocyte subsets were assessed using flow cytometry . Specific mRNAs of Bcl-2 family members were quantified from whole blood by real-time PCR . To test for statistical significance , Kruskal-Wallis testing with Dunn 's multiple comparison test for post hoc analysis was performed . Results In all lymphocyte population s caspase-3 ( p < 0.05 ) was activated , which was reflected in an increased phosphatidylserine externalisation ( p < 0.05 ) . Accordingly , lymphocyte counts were decreased in early severe sepsis . In CD4 + T-cells ( p < 0.05 ) and B-cells ( p < 0.001 ) the Bcl-2 protein was decreased in severe sepsis . Gene expression of the BH3-only Bim was massively upregulated as compared with critically ill patients ( p < 0.001 ) and 51.6-fold as compared with healthy controls ( p < 0.05 ) . Bid was increased 12.9-fold compared with critically ill patients ( p < 0.001 ) . In the group of mitochondrial apoptosis inducers , Bak was upregulated 5.6-fold , while the expression of Bax showed no significant variations . By contrast , the pro-survival members Bcl-2 and Bcl-xl were both downregulated in severe sepsis ( p < 0.001 and p < 0.05 , respectively ) . Conclusions In early severe sepsis a gene expression pattern with induction of the pro-apoptotic Bcl-2 family members Bim , Bid and Bak and a downregulation of the anti-apoptotic Bcl-2 and Bcl-xl proteins was observed in peripheral blood . This constellation may affect cellular susceptibility to apoptosis and complex immune dysfunction in sepsis OBJECTIVE To determine the mechanism for the reduced polymorphonuclear neutrophil exudation to secondary inflammatory sites in critically ill patients with infection and systemic inflammatory response ( sepsis ) . DESIGN Prospect i ve cohort study . SETTING Research laboratory and integrated intensive care unit of a tertiary care university-affiliated teaching hospital . PATIENTS Healthy subjects or critically ill patients with confirmed infection and a systemic inflammatory response ( septic patients ) . MEASUREMENTS AND MAIN RESULTS We found that polymorphonuclear neutrophil delivery to a secondary inflammatory site ( skin window blisters ) is reduced by > 70 % in humans with sepsis , defined as serious infection and a systemic inflammatory response compared with healthy controls . The expression of the endothelial adhesion molecules intercellular adhesion molecule-1 , E-selectin and P-selectin in microvessels from skin biopsies was comparable in the two study groups . Also , CD11a and CD11b levels were equal in circulating polymorphonuclear neutrophils ( PMNs ) from both study groups . Both adhesion molecules were markedly and equally up-regulated during exudation . Circulating PMNs from septic patients showed marked shedding of L-selectin compared to those of healthy controls , with a corresponding increase in their plasma L-selectin levels . An increased concentration gradient between plasma and exu date fluid was found for tumor necrosis factor-alpha and interleukin-8 in septic patients , but not for C5a . The phagocytic and bactericidal capacity of septic patient circulating PMNs was higher then in healthy control patients , but these differences were lost after exudation . There were no major differences in oxidative burst or intracellular calcium flux of circulating PMNs from the two study groups . Polymorphonuclear neutrophil exudation primed both responses to different extents . CONCLUSIONS Septic patients deliver fewer PMNs to secondary inflammatory sites . In addition , neutrophil exudation results in loss of the small priming effect for phagocytosis and bactericidal function induced by sepsis . Failure to produce a gradient to C5a and intravascular shedding of L-selectin may be responsible for this sepsis-induced reduction in neutrophil exudation to secondary inflammatory sites Introduction Lymphocyte apoptosis has been suggested to play a central role in sepsis pathophysiology , and studies in animal models demonstrated that blocking this pathway improves outcome . However , no routine biomarkers of apoptosis are so far available in patients . Thus , the aim of our study was to assess the different biomarkers of apoptosis putatively usable on a routine basis in septic shock . Methods Thirteen septic shock patients ( sample d twice between days 1 to 2 and days 3 to 5 after diagnosis of shock ) and 15 sex-matched and age-matched healthy controls were prospect ively enrolled . Apoptosis was measured in lymphocyte sub population s using flow cytometry ( Annexin-V binding , activated caspase-3 and Bcl-2 expressions ) . Representative pro-apoptotic and anti-apoptotic gene expressions were assessed by quantitative reverse-transcription PCR . Monocyte HLA-DR expression and lymphocyte sub population cell counts were measured as markers of sepsis-induced immune dysfunctions . To test for statistical significance , the Mann-Whitney U test was used with correction by the number of tests performed . Results Flow cytometric measurements of apoptosis in septic shock patients showed an increased Annexin-V binding on CD4 + T cells and an increased active caspase-3 expression on B cells only at days 3 to 5 ( sixfold change and twofold change , respectively ) . Gene expression analysis showed an increased BCL-XL mRNA and an upregulation of the pro-apoptotic genes BID and FAS in septic shock patients ( 10-fold change and fivefold change , respectively ) compared with healthy controls . Conclusions The present study highlights the difficulties encountered in monitoring apoptosis on a routine basis in septic patients , whereas in the same sampling conditions and on the same patients , HLA-DR expression and lymphocyte sub population cell counts showed characteristics described in the literature . However , pro-apoptotic genes BID and FAS appear to constitute promising apoptosis markers in our h and OBJECTIVES The purpose of this study was to determine whether apoptosis is a major mechanism of cell death in patients with sepsis . The activities of caspase-3 and the antiapoptotic protein , BCL-2 , were investigated also . DESIGN A prospect i ve study of 20 patients who died of sepsis and multiple organ dysfunction was performed . The control group of 16 patients consisted of critically ill , nonseptic patients who were evaluated either prospect ively ( 7 ) or retrospectively ( 9 ) . In addition , normal colon sections from seven patients who had bowel resections were included . Apoptosis was evaluated in hematoxylin and eosin-stained specimens by deoxyuridine triphosphate nick end-labeling ( TUNEL ) and by DNA gel electrophoresis . SETTING Two academic medical centers . PATIENTS Critically ill patients . MEASUREMENTS AND MAIN RESULTS In septic patients , apoptosis was detected in diverse organs by all three methods with a predominance in lymphocytes and intestinal epithelial cells . Hematoxylin and eosin-stained specimens from septic patients demonstrated at least focal apoptosis in 56.3 % of spleens , 47.1 % of colons , and 27.7 % of ileums . Indirect evidence of lymphocyte apoptosis in septic patients included extensive depletion of lymphocytes in white pulp and a marked lymphocytopenia in 15 of 19 patients . Hematoxylin and eosin from nonseptic patients ' tissues revealed a low level of apoptosis in one patient only . The TUNEL method increased in positivity with a delay in tissue fixation and was highly positive in many tissues from both septic and nonseptic patients . Immunohistochemical staining for active caspase-3 showed a marked increase in septic vs. nonseptic patients ( p < .01 ) , with > 25 % to 50 % of cells being positive focally in the splenic white pulp of six septic but in no nonseptic patients . CONCLUSIONS We conclude that caspase-3-mediated apoptosis causes extensive lymphocyte apoptosis in sepsis and may contribute to the impaired immune response that characterizes the disorder BACKGROUND Surgery and anesthesia cause depression of cell-mediated immunity in the postoperative period , including a reduction in the numbers of circulating lymphocytes . It has been cl aim ed that this immunosuppression is associated with an increased incidence of postoperative infections . HYPOTHESIS Lymphocytopenia following surgical trauma depends on a dysregulated expression of death/ and survival factors associated with apoptosis that , in turn , interferes with the occurrence of postsurgical infections . DESIGN Fifteen subjects undergoing elective surgery under general anesthesia entered the study . The data of the patients who had infections during the postoperative outcome were compared with the data of those who did not . The data were collected prospect ively . MAIN OUTCOME MEASURES Peripheral blood sample s were drawn before the operation , and 24 hours and 96 hours after the operation . Lymphocytes were isolated and examined for quantification and phenotypic analysis of apoptosis using the 7-amino-actinomycin D method , as well as for Fas and Fas lig and , interleukin 1-converting enzyme p20/caspase-1 , Bcl-2 , and p35 expression . The rate of apoptotic cells was correlated with the incidence of postoperative infections . SETTING University hospital . RESULTS Twenty-four hours after surgery , CD4(+ ) and CD8(+ ) cells exhibited a significantly higher frequency of apoptosis as well as of Fas and Fas lig and and interleukin 1-converting enzyme p20/caspase-1 expressions than preoperatively . This increase was paralleled by a significant down-regulation of antiapoptotic factors such as Bcl-2 . However , the expression of the proapoptotic factor p35 was reduced . In addition , we found a relationship between the rate of the apoptotic CD8(+ ) subset and the occurrence of infectious complications during the postoperative course . At 96 hours after surgery , the variables studied returned to the baseline levels . CONCLUSIONS In the early postoperative period , surgical trauma under general anesthesia induces an intracellular perturbation on peripheral lymphocytes , result ing in both up-regulation of death-signaling factors and down-regulation of survival-signaling factors . The increased apoptosis of CD8(+ ) lymphocytes , but not of CD4(+ ) cells , seemed to be associated with a greater risk of postsurgical infections BACKGROUND There have been conflicting reports on the efficacy of recombinant human activated protein C , or drotrecogin alfa ( activated ) ( DrotAA ) , for the treatment of patients with septic shock . METHODS In this r and omized , double-blind , placebo-controlled , multicenter trial , we assigned 1697 patients with infection , systemic inflammation , and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA ( at a dose of 24 μg per kilogram of body weight per hour ) or placebo for 96 hours . The primary outcome was death from any cause 28 days after r and omization . RESULTS At 28 days , 223 of 846 patients ( 26.4 % ) in the DrotAA group and 202 of 834 ( 24.2 % ) in the placebo group had died ( relative risk in the DrotAA group , 1.09 ; 95 % confidence interval [ CI ] , 0.92 to 1.28 ; P=0.31 ) . At 90 days , 287 of 842 patients ( 34.1 % ) in the DrotAA group and 269 of 822 ( 32.7 % ) in the placebo group had died ( relative risk , 1.04 ; 95 % CI , 0.90 to 1.19 ; P=0.56 ) . Among patients with severe protein C deficiency at baseline , 98 of 342 ( 28.7 % ) in the DrotAA group had died at 28 days , as compared with 102 of 331 ( 30.8 % ) in the placebo group ( risk ratio , 0.93 ; 95 % CI , 0.74 to 1.17 ; P=0.54 ) . Similarly , rates of death at 28 and 90 days were not significantly different in other predefined subgroups , including patients at increased risk for death . Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group ( P=0.81 ) . CONCLUSIONS DrotAA did not significantly reduce mortality at 28 or 90 days , as compared with placebo , in patients with septic shock . ( Funded by Eli Lilly ; PROWESS-SHOCK Clinical Trials.gov number , NCT00604214 . ) Objective : To compare the respiratory burst of neutrophils in sepsis and control patients using lipopolysaccharide ( LPS ) , autologous plasma , and a combination of the two . Design : Prospect i ve , consecutive case study . Setting : A 16-bed intensive care unit ( ICU ) in a university teaching hospital . Interventions : None . Patients : Plasma was obtained from 23 healthy patients scheduled for minor surgery immediately prior to induction of anesthesia ( controls ) and from 23 ICU patients within 24 h of diagnosis of sepsis or septic shock . Measurements and main results : Respiratory burst was determined by lucigenin chemiluminescence expressed as mean ± SEM of peak values of relative light units per neutrophil . There were no significant differences between neutrophils of septic patients and controls for the stimuli saline , phorbol myristate acetate , formyl-methionyl-leucyl-phenylalenine , and LPS alone . Septic patients showed a lower respiratory burst than controls ( p < 0.05 ) under the following stimuli : plasma alone ( 5911 ± 803 vs 15 397 ± 3038 ) and LPS and plasma combined ( 13 857 ± 1537 vs 23 026 ± 2640 ) . However , when stimulated with plasma after priming with LPS , septic patients elicited a higher value than control subjects ( 11 373 ± 1758 vs 5987 ± 1234 , p < 0.05 ) . Conclusions : ( 1 ) Some components of the plasma of septic patients may have a profound effect on neutrophil response ; ( 2 ) plasma as a respiratory burst stimulus differentiates between sepsis and non-sepsis sample s better than other common stimuli ; ( 3 ) pre caution s must be taken when using plasma together with LPS because of the different response depending on whether LPS-priming precedes the plasma stimulus or both are introduced simultaneously and whether septic or nonseptic plasma is used Objective To analyze postoperative leukocyte functions in patients undergoing hemihepatectomy , and to assess the effect of treatment with the endotoxin-neutralizing agent bactericidal/permeability-increasing protein ( rBPI21 ) . Summary Background Data Extensive liver resection is associated with a high incidence of infectious complications . Because elimination of pathogenic microorganisms occurs mainly by leukocytes , this increased rate of infections is most likely due to an impaired function of these cells . Endotoxin , translocated from the gut into the systemic circulation as a result of increased gut permeability and reduced hepatic clearance function after major liver resection , may play an important role in the impairment of posthepatectomy leukocyte function . Methods To investigate whether hemihepatectomy results in impaired leukocyte functions and to determine the role of endotoxin in this process , leukocyte oxidative burst and leukocyte antigen expression were studied in three groups of patients : patients undergoing a hemihepatectomy and receiving rBPI21 treatment , patients undergoing hemihepatectomy and receiving placebo , and as an extra control group patients undergoing other major abdominal surgeries . Blood sample s were collected before surgery , 2 hours after surgery , and at days 1 , 2 , 5 , and 7 . Phorbol myristate acetate-stimulated oxidative burst was measured using dihydrorhodamine , and leukocyte surface expression of the antigens CD11b , CD16 , and CD14 was investigated by indirect immunofluorescence . Both oxidative burst and membrane surface expression were quantified by flow cytometry . An indication of the antiendotoxin effect of rBPI21 treatment was provided by assessment of plasma lipopolysaccharide binding protein ( LBP ) levels by enzyme-linked immunosorbent assay . Results The oxidative burst in the hemihepatectomized patients receiving placebo and the controls increased 2 hours after surgery , whereas it decreased in the rBPI21-treated patients , result ing in significant differences between the groups . On day 1 , neutrophil CD11b expression and monocyte CD14 expression in the rBPI21-treated patients and controls were significantly lower than in the placebo group . At 2 hours , CD16 expression in the placebo-treated patients was significantly higher than in the rBPI21-treated patients and controls . On day 5 and day 7 , plasma LBP levels were significantly higher in the placebo-treated patients compared with the rBPI21-treated patients . Conclusions The results of this study show that patients undergoing major liver resection have an increased activation of leukocytes compared with those undergoing other major abdominal surgery . This enhanced activation may contribute to the increased risk of infection in these patients . Administration of the endotoxin-neutralizing agent rBPI21 to hemihepatectomy patients was shown to reduce plasma LBP levels , to preserve leukocyte functions partially , and to reduce leukocyte activation to the level of other , nonhepatic abdominal surgery BACKGROUND Aging is associated with a decline in immune function . This may contribute to decreased ability of an elderly patient to mount an appropriate innate inflammatory response when injured . This study examined elderly trauma patients to determine whether there was a difference in neutrophil response to injury when compared with controls . METHODS This prospect i ve , observational , cohort study compared neutrophil function in 24 injured elderly ( older than 65 years ) patients admitted to our trauma center to control groups of noninjured individuals ( 11 elderly and 17 young ) . Blood sample s were also taken from the injured elderly group within 48 hours of trauma and subsequently at two periods during their hospital stay . A single blood sample was obtained from the noninjured control groups . Neutrophils were analyzed for CD18 expression , stimulated oxidative burst , apoptosis , and IL-10 . Results were compared using one-way analysis of variance ( alpha 0.05 ) . This study was approved by the Institutional Review Board . RESULTS Twenty-four injured elderly subjects were enrolled : mean injury severity score 15.3 , average age 74.6 years , 92 % survival , 100 % blunt trauma . CD18 levels in the elderly injured subjects for all three time periods were significantly higher than both control groups . When evaluated between controls , CD18 for the noninjured elderly ( NIE ) was also significantly higher than the noninjured young ( NIY ) . The neutrophil stimulated oxidative burst in the injured elderly subjects at time periods 1 , 2 , and 3 was not significantly different from the NIY controls . However , the injured elderly had a significantly higher oxidative burst at time period 3 than the NIE controls . Apoptosis in the injured elderly subjects was significantly lower in all three time periods than the NIY . There was no difference in apoptosis between the injured elderly subjects when compared with the NIE controls . There was no significant difference in IL-10 expression among groups . CONCLUSION Injury results in differences in innate immune function in the elderly when compared with controls . The clinical significance of this is uncertain and warrants further investigation BACKGROUND The optimal target range for blood glucose in critically ill patients remains unclear . METHODS Within 24 hours after admission to an intensive care unit ( ICU ) , adults who were expected to require treatment in the ICU on 3 or more consecutive days were r and omly assigned to undergo either intensive glucose control , with a target blood glucose range of 81 to 108 mg per deciliter ( 4.5 to 6.0 mmol per liter ) , or conventional glucose control , with a target of 180 mg or less per deciliter ( 10.0 mmol or less per liter ) . We defined the primary end point as death from any cause within 90 days after r and omization . RESULTS Of the 6104 patients who underwent r and omization , 3054 were assigned to undergo intensive control and 3050 to undergo conventional control ; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients , respectively . The two groups had similar characteristics at baseline . A total of 829 patients ( 27.5 % ) in the intensive-control group and 751 ( 24.9 % ) in the conventional-control group died ( odds ratio for intensive control , 1.14 ; 95 % confidence interval , 1.02 to 1.28 ; P=0.02 ) . The treatment effect did not differ significantly between operative ( surgical ) patients and nonoperative ( medical ) patients ( odds ratio for death in the intensive-control group , 1.31 and 1.07 , respectively ; P=0.10 ) . Severe hypoglycemia ( blood glucose level , < or = 40 mg per deciliter [ 2.2 mmol per liter ] ) was reported in 206 of 3016 patients ( 6.8 % ) in the intensive-control group and 15 of 3014 ( 0.5 % ) in the conventional-control group ( P<0.001 ) . There was no significant difference between the two treatment groups in the median number of days in the ICU ( P=0.84 ) or hospital ( P=0.86 ) or the median number of days of mechanical ventilation ( P=0.56 ) or renal-replacement therapy ( P=0.39 ) . CONCLUSIONS In this large , international , r and omized trial , we found that intensive glucose control increased mortality among adults in the ICU : a blood glucose target of 180 mg or less per deciliter result ed in lower mortality than did a target of 81 to 108 mg per deciliter . ( Clinical Trials.gov number , NCT00220987 . BACKGROUND Previously , we have demonstrated that surgical stress rapidly induced transient hyporesponsiveness of blood cells to endotoxin and that monocyte mCD14 and HLA-DR expression decreased soon after the start of surgery under general anaesthesia . This study was design ed to investigate the effects of epidural anaesthesia on surgical stress-induced immunosuppression in patients undergoing upper abdominal surgery . METHODS After having obtained informed consent , patients were r and omly allocated to receive general anaesthesia ( Group G ) or general anaesthesia with epidural anaesthesia ( Group E ) . Perioperative changes in neutrophil phagocytic activity , neutrophil respiratory burst activity , monocyte mCD14 and HLA-DR expression , plasma IL-10 concentration , and the LPS-induced TNF-alpha production in whole blood were measured . RESULTS Surgical stress rapidly depressed neutrophil phagocytic activity , monocyte mCD14 and HLA-DR expression , and LPS-induced TNF-alpha production ex vivo ( P < 0.05 vs preoperation ) in both Group G and Group E. In contrast , the plasma IL-10 concentration increased significantly 2 h after the start of surgery ( P < 0.05 ) in both groups . There were no significant differences between the two groups . The neutrophil respiratory burst activity did not change during the operation in either group . CONCLUSION This study showed that the innate immune system is suppressed from the early period of upper abdominal surgery . Subgroup analysis suggested that epidural anaesthesia to T4 dermatome as well as general anaesthesia may not protect patients from this immunosuppression . These results in part explain the impairment of host-defense mechanisms seen in the perioperative period Background Surgery can cause endotoxemia , and endotoxin aggregates to Toll-like receptors and acts proinflammatory ; repetitive endotoxin application can cause tolerance . The objective of the study is to characterize early inflammatory response and expression of TLR2/4 during major abdominal surgery . Material s and methods A prospect i ve controlled study of 20 patients with elective major abdominal surgery was performed . Blood sample s were collected before and at a defined time after surgery . Endotoxemia , capability of plasma to inactivate endotoxin , cytokine release of LPS-stimulated mononuclear cells , quantitative TLR mRNA expression , and plasma concentrations of TNFα , IL-6 , C-reactive protein ( CRP ) , α1-acid glycoprotein , transferrin , and albumin were measured . Results Surgery caused endotoxemia ( p = 0.053 ) , and the capability of plasma to inactivate endotoxin was reduced ( p = 0.0002 ) . Two hours postoperatively , the plasma concentrations of TNFα and IL-6 peaked significantly , but the liberation capacity of mononuclear cells for cytokines ( TNFα , IL-1β , IL-6 ) was significantly reduced . The concentration of CRP and α1-acid glycoprotein peaked 48 h postoperatively , but those of transferrin and albumin were significantly decreased ( p < 0.001 , respectively ) . Median mRNA expression of TLR2 and TLR4 of mononuclear cells was not altered , and there was no obvious trend over time . Conclusion Major abdominal surgery is associated with endotoxemia , reduced capability of plasma to inactivate endotoxin , cytokine kinetics resembling those of healthy man after experimentally given LPS , and substantial acute-phase reaction . The cytokine liberation of mononuclear cells suggests a state of postoperative endotoxin tolerance . Despite these substantial changes , trends in TLR2/4 expression are not obvious OBJECTIVE To examine the relationship between circulating interleukin-10 ( IL-10 ) and the occurrence of lymphocyte apoptosis after surgical/anesthesia trauma . METHODS Data were collected prospect ively on 18 adult patients undergoing elective major surgery . Blood sampling for assessment of lymphocyte apoptosis and IL-10 levels was performed on the day before surgery ( t(0 ) ) and at 24 and 96 hours after operation ( t(1 ) and t(2 ) , respectively ) . After lymphocyte isolation , quantification of apoptosis was made by staining apoptotic cells with 7-amino-actinomycin D. Plasma IL-10 concentrations were measured using enzyme-linked immunosorbent assay . RESULTS A significantly increased frequency of apoptotic CD4(+ ) and CD8(+ ) cells ( p < 0.05 ) was observed at t1 measurement ( 8.10 % + /- 0.58 % and 12.21 % + /- 1.47 % for CD4(+ ) and CD8(+ ) , respectively ) compared with preoperative values ( 1.53 % + /- 0.38 % and 1.32 % + /- 0.45 % for CD4(+ ) and CD8(+ ) , respectively ) . Plasma IL-10 levels showed a significant elevation at both t(1 ) and t(2 ) times , peaking at t(1 ) . At t(1 ) , IL-10 levels were correlated with the frequency of CD4(+ ) and CD8(+ ) apoptotic lymphocytes ( r = 0.78 , p = 0.0005 for IL-10 vs. apoptotic CD4(+ ) ; r = 0.71 , p = 0.003 for IL-10 vs. apoptotic CD8(+ ) ) . CONCLUSION Surgical trauma is associated with a significant but transient increase in lymphocyte commitment to apoptosis and IL-10 production . The exact relationship linking the overproduction of IL-10 with lymphocyte apoptosis after a surgical operation is still elusive and requires further investigation BACKGROUND Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin . METHODS In this multicenter , r and omized , double-blind , placebo-controlled trial , we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days ; the dose was then tapered during a 6-day period . At 28 days , the primary outcome was death among patients who did not have a response to a corticotropin test . RESULTS Of the 499 patients in the study , 233 ( 46.7 % ) did not have a response to corticotropin ( 125 in the hydrocortisone group and 108 in the placebo group ) . At 28 days , there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin ( 39.2 % in the hydrocortisone group and 36.1 % in the placebo group , P=0.69 ) or between those who had a response to corticotropin ( 28.8 % in the hydrocortisone group and 28.7 % in the placebo group , P=1.00 ) . At 28 days , 86 of 251 patients in the hydrocortisone group ( 34.3 % ) and 78 of 248 patients in the placebo group ( 31.5 % ) had died ( P=0.51 ) . In the hydrocortisone group , shock was reversed more quickly than in the placebo group . However , there were more episodes of superinfection , including new sepsis and septic shock . CONCLUSIONS Hydrocortisone did not improve survival or reversal of shock in patients with septic shock , either overall or in patients who did not have a response to corticotropin , although hydrocortisone hastened reversal of shock in patients in whom shock was reversed . ( Clinical Trials.gov number , NCT00147004 . Background and objective : Propofol has been shown to inhibit a variety of functions of neutrophils in vitro , but there is a lack of in vivo data . To analyse the effects of propofol on neutrophil function in vivo we chose to investigate cataract surgery since it represents a small surgical procedure with minimal immunomodulatory effects induced by surgery . We sought to analyse any immunosuppressive effects of propofol after short‐term administration in vivo in comparison to local anaesthesia as well as to in vitro effects of propofol . Methods : The study was design ed as an open r and omized trial enrolling 20 patients undergoing general or local anaesthesia . The neutrophil oxidative response and propofol plasma concentration were assessed prior , during and after anaesthesia . Neutrophil function was determined flow cytometrically based on dihydrorhodamine 123 oxidation . Results : Propofol concentrations which yielded a marked suppression in vitro did not alter the neutrophil oxidative response during cataract surgery in vivo . However , after local anaesthesia the neutrophil oxidative response declined to 37 % , compared to the control response prior to anaesthesia . Conclusions : Although we could detect the well established suppression of neutrophil function by propofol in vitro it was not evident in vivo . This may be due to compensating effects on neutrophil function during surgery in vivo . The decline in the neutrophil oxidative response in the local anaesthesia group might be due to increased stress and catecholamine concentrations or a direct interaction of local anaesthetics with neutrophil intracellular signalling OBJECTIVE To detect T cell apoptosis in reduced peripheral lymphocyte counts in patients having major operations . DESIGN Prospect i ve study . SETTING University hospital , Japan . SUBJECTS 11 patients having oesophagectomy and 5 having laparoscopic cholecystectomy . INTERVENTIONS To investigate T cell apoptosis we detected DNA fragmentation using electrophoresis , and T-cell receptor-gamma ( TCR-gamma ) gene amplification using polymerase chain reaction ( PCR ) in serum . MAIN OUTCOME MEASURES Peripheral lymphocyte count and DNA extracted from the serum preoperatively and on postoperative days 1 , 3 , 5 , and 7 . RESULTS The lymphocyte count decreased significantly until day 5 and then increased in the patients who had had oesophagectomy . DNA fragmentation and PCR products for the TCRgamma variable region gene were found in the serum DNA of 10 patients until day 5 . No DNA fragmentation or PCR products were found in the serum of patients who had had laparoscopic cholecystectomy . CONCLUSION These results suggest that transient T cell apoptosis occurs after major operations STUDY OBJECTIVE To examine the influence of abdominal colectomy with combined general anesthesia and epidural analgesia versus general anesthesia on apoptosis of circulating lymphocytes . DESIGN Prospect i ve , r and omized , clinical comparison study . SETTING Tertiary-care general hospital . PATIENTS 40 ASA physical status I and II patients undergoing elective open colectomy for nonmetastatic colon carcinoma . INTERVENTIONS Patients were r and omly allocated to two groups to receiver either general anesthesia alone ( Group G ) or general anesthesia combined with epidural analgesia ( Group C ) . Group C comprised 21 patients while 19 patients constituted Group G. All patients underwent median longitudinal laparotomy . MEASUREMENTS Blood sample s were collected preoperatively and 24 hours postoperatively for measurement of lymphocyte apoptosis , serum cortisol , C-reactive protein ( CRP ) , and erythrocyte sedimentation rate ( ESR ) . MAIN RESULTS There were no differences between the two groups in age , weight , or duration of surgery . No significant alterations in total lymphocyte counts , as well as in lymphocyte sub population s ( early apoptotic , late apoptotic , viable , and necrotic ) , were observed between the general and combined anesthesia groups . Cortisol , ESR , and CRP were significantly increased postoperatively in both groups . Group C presented with lower serum cortisol levels postoperatively than Group G ( b = -5.38 , CI95 % : -8.72 to -2.05 , P = 0.002 ) . CONCLUSIONS Epidural block could not suppress postoperative lymphocyte apoptosis , increases in cortisol , CRP , or ESR compared with general anesthesia Objectives The purpose of this study was to examine the pattern of tumor necrosis factor (TNF)-&agr ; and interleukin (IL)-10 release in endotoxin-stimulated septic monocytes and to determine the role of IL-10 and transforming growth factor (TGF)-&bgr ; in monocyte hyporesponsiveness during septic shock . Design Monocytes isolated from ten healthy controls and ten patients with septic shock were incubated with endotoxin and cytokine release was assessed . Next , normal monocytes were incubated with either normal or septic serum and stimulated with endotoxin . Finally , normal monocytes were incubated with septic serum either with anti-IL-10 antibodies or anti-TGF-&bgr ; antibodies and then stimulated with endotoxin . Measurements TNF-&agr ; , IL-10 , and TGF-&bgr ; levels were measured in the serum and in culture supernatants by enzyme-linked immunosorbent assay . Setting Research laboratory . Main Results IL-10 and TNF-&agr ; levels were significantly increased in septic serum , whereas TGF-&bgr ; levels were not different from controls . Normal monocytes increased TNF-&agr ; and IL-10 release in response to endotoxin . In contrast , septic monocyte TNF-&agr ; release was attenuated in response to endotoxin ( 1.8 ± 0.5 vs. 1.0 ± 0.4 ng/mL , stimulated vs. baseline ) , whereas IL-10 release increased significantly from baseline ( 173 ± 91 vs. 8 ± 4 pg/mL , stimulated vs. baseline ) . Incubation of normal monocytes with septic serum attenuated TNF-&agr ; release in response to endotoxin ( 32 % ± 8 % of normal serum;p < .01 ) , whereas IL-10 release was increased ( 285 % ± 84 % of normal serum;p < .05 ) . When normal monocytes were incubated with septic serum combined with anti-IL-10 antibodies , TNF-&agr ; release increased significantly to 75 % ± 17 % of normal serum ( p < .05 vs. septic serum alone ) . Incubation of normal monocytes with anti-TGF-&bgr ; antibodies did not significantly affect either TNF-&agr ; or IL-10 release in response to endotoxin . Conclusion Monocytes from patients with septic shock exhibit persistent IL-10 release at a time when TNF-&agr ; release is down-regulated . The continued release of IL-10 may contribute to impairment of monocyte proinflammatory cytokine release and the development of immune dysfunction in septic shock |
12,401 | 26,173,724 | NMES combined with other intervention modalities can be considered as a treatment option that provides improvements in spasticity and range of motion in patients after stroke . | BACKGROUND AND PURPOSE Neuromuscular electric stimulation ( NMES ) has been used to reduce spasticity and improve range of motion in patients with stroke .
However , contradictory results have been reported by clinical trials .
A systematic review of r and omized clinical trials was conducted to assess the effect of treatment with NMES with or without association to another therapy on spastic muscles after stroke compared with placebo or another intervention . | Background and Purpose — The effectiveness of functional electrical stimulation ( FES ) has been investigated in chronic hemiplegia . The present study examines whether FES , given during acute stroke , was more effective in promoting motor recovery of the lower extremity and walking ability than st and ard rehabilitation alone . Methods — Forty-six subjects , 70.9±8.0 years old and 9.2±4.1 days after stroke , were assigned r and omly to 1 of 3 groups receiving st and ard rehabilitation with FES or placebo stimulation or alone ( control ) . FES was applied 30 minutes and placebo stimulation 60 minutes , 5 days per week for 3 weeks . Outcome measurements included composite spasticity score , maximum isometric voluntary contraction of ankle dorsi-flexors and planter-flexors , and walking ability . They were recorded before treatment , weekly during the 3-week treatment , and at week 8 after stroke . Results — No significant differences were found in the baseline measurements . After 3 weeks of treatment , there was a significant reduction in the percentage of composite spasticity score , and a significant improvement in the ankle dorsiflexion torque , accompanied by an increase in agonist electromyogram and a reduction in electromyogram cocontraction ratio in the FES group , when compared with the other 2 groups ( P<0.05 ) . All subjects in the FES group were able to walk after treatment , and 84.6 % of them returned home , in comparison with the placebo ( 53.3 % ) and control ( 46.2 % , P<0.05 ) groups . Conclusions — Fifteen sessions of FES , applied to subjects with acute stroke plus st and ard rehabilitation , improved their motor and walking ability to the degree that more subjects were able to return to home Background and Purpose — Severe upper limb paresis is a major contributor to disability after stroke . This study investigated the efficacy of a new nonrobotic training device , the Sensorimotor Active Rehabilitation Training ( SMART ) Arm , that was used with or without electromyography-triggered electrical stimulation of triceps brachii to augment elbow extension , permitting stroke survivors with severe paresis to practice a constrained reaching task . Methods — A single-blind , r and omized clinical trial was conducted with 42 stroke survivors with severe and chronic paresis . Thirty-three participants completed the study , of whom 10 received training using the SMART Arm with electromyography-triggered electrical stimulation , 13 received training using the SMART Arm alone , and 10 received no intervention ( control ) . Training consisted of 12 1-hour sessions over 4 weeks . The primary outcome measure was “ upper arm function , ” item 6 of the Motor Assessment Scale . Secondary outcome measures included impairment measures ; triceps muscle strength , reaching force , modified Ashworth scale ; and activity measures : reaching distance and Motor Assessment Scale . Assessment s were administered before ( 0 weeks ) and after training ( 4 weeks ) and at 2 months follow-up ( 12 weeks ) . Results — Both SMART Arm groups demonstrated significant improvements in all impairment and activity measures after training and at follow-up . There was no significant difference between these 2 groups . There was no change in the control group . Conclusions — Our findings indicate that training of reaching using the SMART Arm can reduce impairment and improve activity in stroke survivors with severe and chronic upper limb paresis , highlighting the benefits of intensive task-oriented practice , even in the context of severe paresis To compare the efficacy of electromyography (EMG)-triggered ( active ) neuromuscular electrical stimulation ( NMES ) and passive NMES in enhancing the upper extremity ( UE ) motor and functional recovery of subacute and chronic stage stroke patients . Thirty-one hemiplegic patients were r and omly assigned to active NMES ( n=11 ) , passive NMES ( n=10 ) , and control ( sham stimulation ) ( n=10 ) groups . Each treatment regimen was applied five times per week for 45 min for 3 weeks . All of the patients performed the same neurophysiologic exercise program for 45 min five times per week for 3 weeks . Patients were assessed by the UE component of the Fugl-Meyer Motor Assessment ( UE-FMA ) , the self-care component of the Functional Independence Measure ( self-care FIM ) , the Motor Activity Log ( MAL ) , goniometric measurements of active wrist and metacarpophalangeal joint extension , surface EMG potentials , grip strength , and the modified Ashworth scale in a blinded manner . Data were obtained before and at the end of the treatment . Participants were similar in all clinical and demographic features ( P>0.05 ) . All groups were comparable with respect to UE-FMA , MAL , self-care FIM , wrist and finger flexor spasticity , active range of motion ( ROM ) , grip strength , and surface EMG potentials before treatment ( P>0.05 ) . The active ROM , grip strength , FMA , FIM , surface EMG potentials , and MAL : amount of use were significantly improved in the EMG-triggered NMES group compared with the controls ( P<0.05 ) . The active wrist extension ROM and FMA scores were significantly improved in the passive NMES group compared with the controls ( P<0.05 ) . There were no statistically significant differences between active and passive NMES groups in any of the parameters evaluated at the end of the treatment ( P>0.05 ) . Both active and passive NMES as adjuvant therapy in the neurophysiologic exercise program effectively enhanced the UE motor and functional recovery of stroke survivors . Vergleich der Wirksamkeit der elektromyographisch (EMG)-getriggerten ( aktiven ) neuromuskulären Elektrostimulation ( NMES ) und passiven NMES zur Verbesserung der motorischen und funktionellen Erholung der oberen Extremitäten bei Schlaganfallpatienten in der subakuten und chronischen Phase . Insgesamt 31 einseitig gelähmte Patienten wurden r and omisiert den aktiven NMES- ( n=11 ) , passiven NMES- ( n=10 ) und Kontrollgruppen ( Sham-Stimulation ) ( n=10 ) zugeordnet . Jede Therapie wurde fünfmal pro Woche jeweils 45 Minuten lang über drei Wochen hinweg angew and t. Alle Patienten unterzogen sich fünfmal pro Woche jeweils 45 Minuten lang über drei Wochen hinweg dem gleichen neurophysiologischen Übungsprogramm . Die Beurteilung der Patienten erfolgte anh and der Komponente “ obere Extremitäten ” des motorischen Funktionstests nach Fugl-Meyer ( UE-FMA ) , der Selbstversorgungskomponente des funktionalen Selbständigkeitsindexes ( Selbstversorgung FIM ) , des Motor Activity Log ( MAL ) , der goniometrischen Messung der aktiven H and gelenk- und Fingergrundgelenkextension , der Oberflächen-EMG-Potenziale , der Griffstärke und der modifizierten Ashworth-Skala in verblindeter Form . Date n wurden vor und nach Abschluss der Beh and lung erfasst . Die Teilnehmer schnitten bei allen klinischen und demographischen Merkmalen ähnlich ab ( P<0.05 ) . Alle Gruppen waren vergleichbar hinsichtlich UE-FMA , MAL , Selbstversorgungs-FIM , Spastizität der H and gelenks- und Fingerbeuger , aktiver Bewegungsamplitude ( ROM ) , Griffstärke und Oberflächen-EMG-Potenziale vor der Beh and lung ( P>0.05 ) . Aktive ROM , Griffstärke , FMA , FIM , Oberflächen-EMG-Potenziale und MAL : Das Ausmaß der Anwendung war in der EMG-getriggerten NMES-Gruppe verglichen mit den Teilnehmern der Kontrollgruppe signifikant verbessert ( P<0.05 ) . Die ROM- und FMA-Scores der aktiven H and gelenkextension waren in der passiven NMES-Gruppe verglichen mit der Kontrollgruppe signifikant verbessert ( P<0.05 ) . Es lagen keine statistisch signifikanten Unterschiede zwischen den aktiven und passiven NMES-Gruppen bei den zu Ende der Beh and lung beurteilten Parametern vor ( P>0.05 ) . Die aktive und passive NMES als Begleittherapie des neurophysiologischen Übungsprogramms verbesserte die motorische und funktionelle Genesung der oberen Extremitäten von Überlebenden eines Schlaganfalls effektiv . El objetivo de este estudio fue comparar la eficacia de la estimulación eléctrica neuromuscular ( EENM ) ( activa ) mediante electromiografía ( EMG ) y EENM pasiva con respecto a la mejora de la recuperación motora y funcional de las extremidades superiores ( ES ) en pacientes con accidente cerebrovascular subagudo y crónico . Treinta y un pacientes hemiplégicos fueron asignados de forma aleatoria al grupo de EENM activa ( n=11 ) , al grupo de EENM pasiva ( n=10 ) y al grupo control ( estímulo falso ) ( n=10 ) . Cada uno de los tratamientos se aplicó cinco veces a la semana durante 45 minutos , durante 3 semanas . Todos los pacientes fueron sometidos al mismo programa de ejercicios neurofisiológicos , con una duración de 45 minutos , cinco veces a la semana durante 3 semanas . Los pacientes fueron analizados mediante el componente de extremidades superiores de la puntuación de Fugl-Meyer ( FM-ES ) , el componente de cuidado personal de la Medida de Independencia Funcional ( MIF-CP ) , el Registro de Actividad Motora ( MAL , por sus siglas en inglés ) , las medidas goniométricas de la extensión articular activa metacarpofalángica y de la muñeca , los potenciales de EMG de superficie , la fuerza de prensión y la escala modificada de Ashworth con enmascaramiento . Se recopilaron datos previamente y posteriormente al tratamiento . Los participantes poseían características clínicas y demográficas similares ( P<0.05 ) . Todos los grupos eran comparables con respecto a FM-ES , MAL , MIF-CP , la espasticidad flexora de la muñeca y el dedo , el rango activo de movimiento ( RM ) , la fuerza de prensión y los potenciales de EMG de superficie antes de comenzar el tratamiento ( P>0.05 ) . El RM activo , la fuerza de prensión , la puntuación de FM , MIF , los potenciales de EMG de superficie y MAL mejoraron significativamente en el grupo de EENM mediante EMG en comparación con el grupo control ( P<0.05 ) . Las puntuaciones de FM y RM activo de la extensión de la muñeca mejoraron significativamente en el grupo de EENM pasiva en comparación con el grupo control ( P<0.05 ) . No se observaron diferencias estadísticamente significativas entre los grupos de EENM activa y pasiva en ninguno de los parámetros evaluados al finalizar el tratamiento ( P>0.05 ) . Tanto la EENM activa como la EENM pasiva , como tratamientos adyuvantes dentro del programa de ejercicios neurofisiológicos , mejoraron efectivamente la recuperación motora y funcional de los supervivientes de accidente cerebrovascular . Comparer l’efficacité de la stimulation électrique neuromusculaire ( NMES ) déclenchée par électromyographie ( EMG ) ( active ) et de la NMES passive dans l’amélioration de la récupération motrice et fonctionnelle des extrémités supérieures ( UE ) chez les patients victimes d’AVC en phase subaiguë et chronique . Trente et un patients hémiplégiques ont été assignés de manière aléatoire à des groupes de NMES active ( n=11 ) , passive ( n=10 ) et de contrôle ( stimulation leurre ) ( n=10 ) . Chaque traitement a été appliqué cinq fois par semaine pendant 45 min pendant 3 semaines . Tous les patients ont suivi le même programme d’exercice neurophysiologique pendant 45 min , cinq fois par semaine , pendant 3 semaines . Les patients ont été évalués en aveugle par la composante UE de l'évaluation motrice de Fugl-Meyer ( UE-FMA ) , la composante de soins auto-administrés de la mesure d’indépendance fonctionnelle ( FIM soins auto-administrés ) , le Motor Activity Log ( MAL ) , les mesures goniométriques du poignet actif et de l’extension de l’articulation métacarpophalangienne , les potentiels EMG de surface , la force de préhension et l'échelle Ashworth modifiée . Les données ont été recueillies avant et à la fin du traitement . Les participants présentaient des caractéristiques cliniques et démographiques semblables ( P<0.05 ) . Tous les groupes étaient comparables en ce qui concerne les paramètres UE-FMA , MAL , FIM soins auto-administrés , spasticité des fléchisseurs du poignet et des doigts , amplitude active des mouvements ( ROM ) , force de préhension et potentiels EMG de surface avant le traitement ( P>0.05 ) . ROM active , force de préhension , FMA , FIM , potentiels EMG de surface et MAL : volume d’utilisation significativement amélioré chez le groupe NMES déclenchée par EMG par rapport au groupe témoin ( P<0.05 ) . Les scores ROM et FMA d’extension du poignet actif ont été considérablement améliorés chez le groupe NMES passive par rapport au groupe témoin ( P<0,05 ) . Il n’a été constaté aucune différence statistiquement significative entre les groupes NMES active et passive dans les paramètres évalués à la fin du traitement ( P>0.05 ) . La NMES active ou passive comme thérapie adjuvante dans le programme d’exercice neurophysiologique a efficacement amélioré la récupération motrice et fonctionnelle UE des patients ayant survécu à un AVC Background . Functional electrical stimulation ( FES ) allows active exercises in stroke patients with upper extremity paralysis . Objective . To investigate the effect of motor training with FES on motor recovery in acute and subacute stroke patients with severe to complete arm and /or h and paralysis . Methods . For this pilot study , 23 acute and subacute stroke patients were r and omly assigned to the intervention ( n = 12 ) and control group ( n = 11 ) . Distributed over 4 weeks , FES training replaced 12 conventional training sessions in the intervention group . An Extended Barthel Index ( EBI ) subscore assessed the performance of activities of daily living ( ADL ) . The Chedoke McMaster Stroke Assessment ( CMSA ) measured h and and arm function and shoulder pain . The Modified Ashworth Scale ( MAS ) assessed resistance to passive movement . Unblinded assessment s were performed prior to and following the end of the training period . Results . The EBI subscore and CMSA arm score improved significantly in both groups . The CMSA h and function improved significantly in the FES group . Resistance to passive movement of finger and wrist flexors increased significantly in the FES group . Shoulder pain did not change significantly . None of the outcome measures , however , demonstrated significant gain differences between the groups . Conclusions . We did not find clear evidence for superiority or inferiority of FES . Our findings , and those of similar trials , suggest that the number of sessions should be at least doubled to test for superiority of FES in these highly impaired patients and approximately 50 participants would have to be assigned to each therapeutic intervention to find significant differences OBJECTIVE Assess the effects of daily neuroprosthetic ( NESS H and master ) functional electrical stimulation in sub-acute stroke . DESIGN Controlled study , patients clinical ly stratified to 2 groups ; no active finger movement , and partial active finger movements , and then r and omized to control and neuroprosthesis groups . Observer blinded evaluations at baseline and completion of the 6-week study . SUBJECTS 22 patients with moderate to severe upper limb paresis 3 - 6 months post-onset . METHODS Patients in day hospital rehabilitation , receiving physical and occupational therapy 3 times weekly . The neuroprosthesis group used the device at home . RESULTS The neuroprosthesis group had significantly greater improvements in spasticity , active range of motion and scores on the functional h and tests ( those with partial active motion ) . Of the few patients with pain and oedema , there was improvement only among those in the neuroprosthesis group . There were no adverse reactions . CONCLUSION Supplementing st and ard outpatient rehabilitation with daily home neuroprosthetic activation improves upper limb outcomes The objective of this study was to evaluate the effects of mirror therapy in combination with biofeedback functional electrical stimulation ( BF-FES ) on motor recovery of the upper extremities after stroke . Twenty-nine patients who suffered a stroke > 6 months prior participated in this study and were r and omly allocated to three groups . The BF-FES + mirror therapy and FES + mirror therapy groups practice d training for 5 × 30 min sessions over a 4-week period . The control group received a conventional physical therapy program . The following clinical tools were used to assess motor recovery of the upper extremities : electrical muscle tester , electrogoniometer , dual-inclinometer , electrodynamometer , the Box and Block Test ( BBT ) and Jabsen Taylor H and Function Test ( JHFT ) , the Functional Independence Measure , the Modified Ashworth Scale , and the Stroke Specific Quality of Life ( SSQOL ) assessment . The BF-FES + mirror therapy group showed significant improvement in wrist extension as revealed by the Manual Muscle Test and Range of Motion ( p < 0.05 ) . The BF-FES + mirror therapy group showed significant improvement in the BBT , JTHT , and SSQOL compared with the FES + mirror therapy group and control group ( p < 0.05 ) . We found that BF-FES + mirror therapy induced motor recovery and improved quality of life . These results suggest that mirror therapy , in combination with BF-FES , is feasible and effective for motor recovery of the upper extremities after stroke Objective : To investigate the therapeutic effect of electrical stimulation on plantarflexor spasticity in stroke patients . Design : A r and omized controlled clinical trial study . Setting : Rehabilitation clinic of Semnan University of Medical Sciences . Subjects : Forty stroke patients ( aged from 42 to 65 years ) with ankle plantarflexor spasticity . Intervention : Fifteen minutes of inhibitory Bobath techniques were applied to one experimental group and a combination of 9 minutes of electrical stimulation on the dorsiflexor muscles and inhibitory Bobath techniques was applied to another group for 20 sessions daily . Main measures : Passive ankle joint dorsiflexion range of motion , dorsiflexion strength test , plantarflexor muscle tone by Modified Ashworth Scale and soleus muscle H-reflex . Results : The mean change of passive ankle joint dorsiflexion in the combination therapy group was 11.4 ( SD 4.79 ) degrees versus 6.1 ( SD 3.09 ) degrees , which was significantly higher ( P = 0.001 ) . The mean change of plantarflexor muscle tonicity measured by the Modified Ashworth Scale in the combination therapy group was -1.6 ( SD 0.5 ) versus -1.1 ( SD 0.31 ) in the Bobath group ( P = 0.001 ) . Dorsiflexor muscle strength was also increased significantly ( P = 0.04 ) in the combination therapy group ( 0.7 ± 0.37 ) compared with the Bobath group ( 0.4 ± 0.23 ) . However , no significant change in the amplitude of H-reflex was found between combination therapy ( -0.41 ± 0.29 ) and Bobath ( -0.3 ± 0.28 ) groups . Conclusion : Therapy combining Bobath inhibitory technique and electrical stimulation may help to reduce spasticity effectively in stroke patients OBJECTIVE To evaluate the therapeutic effects of Functional Electrical Stimulation ( FES ) of the tibialis anterior muscle on plantarflexor spasticity , dorsiflexor strength , voluntary ankle dorsiflexion , and lower extremity motor recovery with stroke survivors . DESIGN We conducted a prospect i ve interventional study . SETTING Rehabilitation ward , physiotherapy unit and gait analysis laboratory . PARTICIPANTS Fifty-one patients with foot drop result ing from stroke . INTERVENTION The functional electrical stimulation ( FES ) group ( n=27 ) received 20 - 30 minutes of electrical stimulation to the peroneal nerve and anterior tibial muscle of the paretic limb along with conventional rehabilitation program ( CRP ) . The control group ( n=24 ) treated with CRP only . The subjects were treated 1 hr per day , 5 days a week , for 12 weeks . MAIN OUTCOME MEASURES Plantarflexor spasticity measured by modified ashworth scale ( MAS ) , dorsiflexion strength measured by manual muscle test ( MMT ) , active/passive ankle joint dorsiflexion range of motion , and lower-extremity motor recovery by Fugl-Meyer assessment ( FMA ) scale . RESULTS After 12 weeks of treatment , there was a significant reduction in a plantarflexor spasticity by 38.3 % in the FES group and 21.2 % in control group ( P < 0.05 ) , between the beginning and end of the trial . Dorsiflexor muscle strength was increased significantly by 56.6 % and 27.7 % in the FES group and control group , respectively . Similarly , voluntary ankle dorsiflexion and lower-extremity motor function improved significantly in both the groups . No significant differences were found in the baseline measurements among groups . When compared with control group , a significant improvement ( p < 0.05 ) was measured in all assessed parameters in the FES group at post-treatment assessment , thus FES therapy has better effect on recovery process in post-stroke rehabilitation . CONCLUSIONS Therapy combining FES and conventional rehabilitation program was superior to a conventional rehabilitation program alone , in terms of reducing spasticity , improving dorsiflexor strength and lower extremity motor recovery in stroke patients QUESTION Does static stretch positioning combined with simultaneous neuromuscular electrical stimulation ( NMES ) in the subacute phase after stroke have beneficial effects on basic arm body functions and activities ? DESIGN Multicentre r and omised trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS Forty-six people in the subacute phase after stroke with severe arm motor deficits ( initial Fugl-Meyer Assessment arm score ≤ 18 ) . INTERVENTION In addition to conventional stroke rehabilitation , participants in the experimental group received arm stretch positioning combined with motor amplitude NMES for two 45-minute sessions a day , five days a week , for eight weeks . Control participants received sham arm positioning ( ie , no stretch ) and sham NMES ( ie , transcutaneous electrical nerve stimulation with no motor effect ) to the forearm only , at a similar frequency and duration . OUTCOME MEASURES The primary outcome measures were passive range of arm motion and the presence of pain in the hemiplegic shoulder . Secondary outcome measures were severity of shoulder pain , restrictions in performance of activities of daily living , hypertonia , spasticity , motor control and shoulder subluxation . Outcomes were assessed at baseline , mid-treatment , at the end of the treatment period ( 8 weeks ) and at follow-up ( 20 weeks ) . RESULTS Multilevel regression analysis showed no significant group effects nor significant time × group interactions on any of the passive range of arm motions . The relative risk of shoulder pain in the experimental group was non-significant at 1.44 ( 95 % CI 0.80 to 2.62 ) . CONCLUSION In people with poor arm motor control in the subacute phase after stroke , static stretch positioning combined with simultaneous NMES has no statistically significant effects on range of motion , shoulder pain , basic arm function , or activities of daily living . TRIAL REGISTRATION NTR1748 BACKGROUND Functional electrical stimulation ( FES ) to patients early after stroke has been proved to improve walking ability . The effects on abilities in activities of daily living ( ADL ) are not clear . OBJECTIVE To investigate the effectiveness of FES in improving lower limb function and ability in ADL of early stroke patients . METHODS Thirty-seven stroke patients were r and omly allocated to st and ard rehabilitation ( SR ) group ( n = 18 ) , and FES group with FES and SR ( n = 19 ) . SR included 60 minutes each for physiotherapy and occupational therapy . FES was delivered for 30 min to induce ankle dorsiflexion and eversion . Treatments were 5 days per week for 3 weeks . Evaluations including the composite spasticity scale ( CSS ) , lower-extremity subscale of Fugl-Myer Assessment ( FMA ) , postural assessment scale for stroke patients ( PASS ) , Berg Balance Scale ( BBS ) , and modified Barthel Index ( MBI ) assessed before treatment , after 2 and 3 week treatment respectively . RESULTS After 2 week treatment , FES group showed a significant reduction of CSS and improvements of FMA , MBI and PASS . After 3 week treatment , FES group showed a further reduction of CSS and also improvement of FMA , MBI and BBS as well . CONCLUSIONS FES on the paretic lower limbs early after stroke improved the mobility and ability in ADL OBJECTIVE To investigate the therapeutic effects of combining electric stimulation ( ES ) with active ankle dorsiflexion while st and ing on a rocker board in subjects with plantarflexor spasticity after stroke . DESIGN R and omized controlled trial . SETTING A rehabilitation medical center . PARTICIPANTS Subjects ( N=15 ) with spastic foot after stroke . INTERVENTIONS Subjects were r and omly assigned to an experimental or a control group . The experimental group received ES of ankle dorsiflexors in concert with a motor training paradigm that required the subject to dorsiflex the ankles in response to a cue while st and ing on a rocker board . After 30 minutes of this exercise , subjects received ambulation training focusing on ankle control for 15 minutes . The control group received general range of motion and strength exercises for 30 minutes , followed by 15 minutes of ambulation training focusing on ankle control . Sessions occurred 3 times a week for 4 weeks . MAIN OUTCOME MEASURES Dynamic spasticity of plantarflexors , dorsiflexor muscle strength , balance performance , gait kinematics , and functional gait performance as assessed by the Emory Functional Ambulation Profile ( EFAP ) were used as outcome measurements . RESULTS The experimental group demonstrated a greater decrease in dynamic ankle spasticity at a comfortable gait speed ( P=.049 ) , a greater improvement in spatial gait symmetry ( P=.015 ) , and a greater improvement in functional gait ability as indicated by the EFAP ( P=.015 ) than the control group . CONCLUSIONS Our results suggest that repeated ES with volitional ankle movements can decrease dynamic ankle spasticity in subjects with stroke . Furthermore , such improvement parallels better gait symmetry and functional gait performance Hara Y , Ogawa S , Muraoka Y : Hybrid power-assisted functional electrical stimulation to improve hemiparetic upper-extremity function . Am J Phys Med Rehabil 2006;85:977–985 . Objective : The effect on spastic hemiparesis of a hybrid therapy consisting of functional electrical stimulation and block therapy was examined . Design : Sixteen consecutively enrolled stroke patients who had spastic upper-extremity impairments more than 1 yr after stroke were recruited for this nonblinded r and omized controlled trial . Patients underwent hybrid functional electrical stimulation therapy on their extensor carpi radialis longus and brevis , extensor digitorum communis , and extensor indicis proprius muscles once or twice a week for 4 mos after motor point blocks at the spastic finger flexor muscles . Surface electrodes picked up the electromyography signal and stimulated those muscles in proportion to the integrated electromyography signal obtained by the functional electrical stimulation device . The root mean square of the extensor carpi radialis longus and extensor digitorum communis maximum voluntary electromyography , active range of motion of wrist extension , finger extension , Modified Ashworth Scale , and two clinical tests were examined before and after training . Results : Root mean square , active range of motion , Modified Ashworth Scale , and two clinical tests showed marked improvement in all patients as compared with the control subjects . Conclusions : The hybrid therapy was effective for patients with chronic spastic hemiparesis . Proprioceptional sensory feedback may have an important role in power-assisted functional electrical stimulation therapy The study tested the spasmolytic effect of Botulinum toxin A in two groups of hemiparetic patients with lower limb spasticity : in the first group ( n = 5 ) 2000 U Dysport were injected into the soleus , tibialis posterior and both heads of gastrocnemius muscles alone ; the second ( n = 5 ) received additional repetitive alternating electrical stimulation of M. tibialis anterior and plantar flexors for 30 min six times per day during the 3 days following the injection . Muscle tone , rated by the Ashworth spasticity score , and gait analysis including recording of vertical ground reaction forces , were assessed before and 4 weeks after injection . The combined treatment proved to be more effective with respect to the clinical ly assessed reduction of muscle tone , gait velocity , stride length , stance- and swing-symmetry ( P < 0.05 ) . The result is discussed with reference to animal experiments demonstrating enhanced toxin uptake and accelerated onset of its paralytic effect by electrical stimulation Objectives : To investigate effects of surface neuromuscular electrical stimulation applied early after stroke to the wrist and finger extensor muscles on upper limb pain , spasticity and contractures in patients with no functional arm movement . Design : Secondary analysis from a Phase II , r and omized , controlled , single-blind study . Setting : An acute hospital stroke unit . Subjects : Patients with no useful arm function within six weeks of a first stroke . Intervention : Patients were r and omized to treatment ( 30-minute sessions of surface neuromuscular stimulation to wrist and finger extensors and 45 minutes of physiotherapy ) or control ( 45 minutes of physiotherapy ) groups . All patients had access to routine care . Treatment was given for six weeks from recruitment . Results : Ninety patients ( 49 % male , median age 74 years ( range 32–98 ) , median time since stroke onset three weeks ( range one to six weeks ) ) were included . Treatment compliance was variable ( mean 28 % ) . The treatment prevented the development of pain ( mean difference in rate of change 0.4 units/week , 95 % confidence interval ( CI ) 0.09 to 0.6 ) . Treatment may have prevented a deterioration in contractures ( quantified by measuring passive range of movement ) in severely disabled patients ( mean rate of deterioration −0.5 deg/week ; 95 % CI −0.9 to −0.06 ) . There were no significant changes in stiffness and spasticity . Conclusion : Surface neuromuscular electrical stimulation reduces pain in stroke patients with a non-functional arm . There was some evidence that treatment with electrical stimulation was beneficial in reducing contractures . Treatment had no effect on spasticity Objective : To investigate whether the combined approach of botulinum toxin type A ( BtxA ) and electrical stimulation was more effective than the toxin alone in the treatment of chronic upper limb spasticity after stroke . Design : R and omized , placebo-controlled study with four treatment groups : 1000 units BtxA ( Dysport ® ) + electrical stimulation ( A ) , 1000 units BtxA ( B ) , placebo + electrical stimulation ( C ) and placebo ( D ) . Setting : A neurological rehabilitation clinic . Subjects : Twenty-four stroke patients with chronic upper limb spasticity after stroke , six patients in each treatment group . Interventions : Intramuscular injection of either toxin or placebo into six upper limb flexor muscles . In group A and C additional electrical stimulation of the injected muscles with surface electrodes , three times half an hour each day for three days . Main outcome measures : Muscle tone rated with the modified Ashworth score , limb position at rest and difficulties encountered during three upper limb motor tasks assessed before and 2 , 6 and 12 weeks after injection . Results : Most improvements were observed in patients of group A. Cleaning the palm ( p = 0.004 ) differed across groups . Pairwise comparison for this target variable showed that group A differed from group B and D ( p < 0.01 ) , but not from C. Indicative across-group differences were obtained for elbow spasticity reduction ( p = 0.011 ) , and improvement of putting the arm through a sleeve ( p = 0.020 ) . Conclusions : The placebo-controlled trial favours the conceptthat electrical stimulation enhances the effectiveness of BtxA in the treatment of chronic upper limb flexor spasticity after stroke Purpose . To assess the effects of daily power-assisted functional electrical stimulation ( FES ) home program therapy in chronic stroke . Methods . A total of 20 consecutively enrolled stroke patients with spastic upper-extremity impairments > 1 year after stroke were recruited for this non-blinded r and omized controlled trial . Subjects were assigned to control and FES groups and followed for 5 months . The FES group used a power-assisted FES device to induce greater muscle contraction by electrical stimulation in proportion to the integrated electromyography ( EMG ) signal picked up on surface electrodes . Target muscles were the extensor carpi radialis longus ( ECRL ) and extensor carpi radialis brevis ( ECRB ) , extensor digitorum communis ( EDC ) , extensor indicis proprius ( EIP ) , and deltoid ( Del ) . Patients underwent 30 ∼ 60 min FES sessions at home about 6 days/week . Root mean square ( RMS ) of ECRL , EDC and Del maximum voluntary EMGs , active range of motion ( ROM ) of wrist and finger extension and shoulder flexion , modified Ashworth scale ( MAS ) , and clinical tests were investigated before and after FES training . Results . The FES group displayed significantly greater improvements in RMS , active ROM , MAS and functional h and tests , and was able to smoothly perform activities of daily life using the hemiplegic upper extremities . Conclusions . Daily power-assisted FES home program therapy can effectively improve wrist and finger extension and shoulder flexion . Proprioceptional sensory feedback might play an important role in power-assisted FES therapy Background . The recovery rate of upper limb function after stroke is poor when compared with independent walking . Therefore , effective methods are warranted for upper limb rehabilitation . Objective . The aim of this study was to investigate the effectiveness of functional electric stimulation ( FES ) with bilateral activities training on upper limb function . Methods . This study was a double-blinded r and omized controlled trial . Twenty patients were recruited 6 months after the onset of stroke and completed 15 training sessions . Participants were r and omly assigned to the FES group or to the control group . Each session consisted of stretching activities ( 10 minutes ) , FES with bilateral tasks ( 20 minutes ) , and occupational therapy treatment ( 60 minutes ) . The participants used a self-trigger mechanism , with an accelerometer as a motion detector , for generating an electric stimulation pattern that was synchronized with the bilateral upper limb activities during the training . The participants in the control group received the same duration of stretching and occupational therapy training except that they just received placebo stimulation with the bilateral tasks . The outcome measures included Functional Test for the Hemiplegic Upper Extremity ( FTHUE ) , Fugl — Meyer Assessment ( FMA ) , grip power , forward reaching distance , active range of motion of wrist extension , Functional Independence Measure , and Modified Ashworth Scale . Results . At baseline comparison , there was no significant difference in both groups . After 15 training sessions , the FES group had significant improvement in FMA ( P = .039 ) , FTHUE ( P = .001 ) , and active range of motion of wrist extension ( P = .020 ) when compared with the control group . Conclusions . Bilateral upper limb training with FES could be an effective method for upper limb rehabilitation of stroke patients after 15 training sessions de Kroon JR , IJzerman MJ , Lankhorst GJ , Zilvold G : Electrical stimulation of the upper limb in stroke : Stimulation of the extensors of the h and vs. alternate stimulation of flexors and extensors . Am J Phys Med Rehabil 2004;83:592–600 . Objective : To investigate whether there is a difference in functional improvement in the affected arm of chronic stroke patients when comparing two methods of electrical stimulation . Design : Explanatory trial in which 30 chronic stroke patients with impaired arm function were r and omly allocated to either alternating electrical stimulation of the extensor and flexor muscles of the h and ( group A ) or electrical stimulation of the extensors only ( group B ) . Primary outcome measure was the Action Research Arm test to assess arm function . Grip strength , Motricity Index , Ashworth Scale , and range of motion of the wrist were secondary outcome measures . Results : Improvement on the Action Research Arm test was 1.0 point in group A and 3.3 points in group B ; the difference in functional gain was 2.3 points ( 95 % confidence interval , −1.06 to 5.60 ) . The success rate ( i.e. , percentage of patients with a clinical ly relevant improvement of > 5.7 points on the Action Research Arm test ) was 27 % in group B ( four patients ) and 8 % in group A ( one patient ) . The differences in functional gain and success rate were not statistically significant , neither were the differences between the two groups on the secondary outcome measures . Conclusion : The difference between the two stimulation strategies was not statistically significant OBJECTIVE To investigate the effect of combined botulinum toxin type A ( BTX ) and functional electric stimulation ( FES ) treatment on spastic drop foot in stroke . DESIGN Nonblinded r and omized controlled trial . SETTING Hospitals . PARTICIPANTS Consecutive sample of 21 ambulant adults within 1 year after stroke with a spastic drop foot , of whom 18 completed the study . INTERVENTIONS The treatment group received BTX injections ( Dysport ) on 1 occasion into the medial and lateral heads of the gastrocnemius ( 200U each ) and tibialis posterior ( 400U each ) muscles and FES , used on a daily basis for 16 weeks to assist walking . Both groups continued with physiotherapy at the same rate . MAIN OUTCOME MEASURES Walking speed , Physiological Cost Index , Modified Ashworth Scale , Rivermead Motor Assessment , and Medical Outcomes Study 36-Item Short-Form Health Survey . RESULTS Walking speed increased over 12 weeks in both control ( P=.020 ) and treatment groups ( nonstimulated , P=.004 ; stimulated , P=.042 ) . The baseline corrected ( analysis of covariance ) increase in mean walking speed at 12 weeks , relative to controls , was.04 m/s ( 95 % confidence interval [CI],.003-.090 ) without stimulation , and .09 m/s ( 95 % CI,.031-.150 ) with stimulation . CONCLUSIONS Combined treatment effectively improved walking and function . A larger study is needed to quantify the treatment effect and to investigate its impact on quality of life OBJECTIVE To determine whether functional electrical stimulation ( FES ) timed to activate the dorsiflexors and plantar flexors during gait improves the walking of adults with hemiplegia . DESIGN R and omized crossover trial . SETTING Outpatient rehabilitation clinic . PARTICIPANTS Adults with hemiplegia ( N=28 ) with a mean age + /- SD of 60+/-10.9 years and 4.9+/-3.8 years postincident . INTERVENTIONS Intervention " A " included 3 months of wearing the FES system , which activated automatically during walking for 6 to 8h/d , 7d/wk , plus walking 1h/d , 6d/wk . Intervention " B " included 3 months of walking 1h/d , 6d/wk without FES . Of the 28 patients who completed the study , 15 were r and omly assigned to group A-B , 13 to group B-A. Crossover occurred at 3 months . MAIN OUTCOME MEASURES Variables were measured at pretreatment , 3 months , and 6 months . Three primary outcomes were selected a priori and included 2 functional variables , the 6-minute walk test and the Emory Functional Ambulatory Profile , and 1 participation variable , the Stroke Impact Scale . Secondary impairment measures included muscle strength and spasticity . Assessment s were done without electrical stimulation . RESULTS In phase 1 , patients who received treatment A ( A-B group ) showed improvement compared with patients who received treatment B ( B-A group ) on the 6-minute walk test ( P=.02 ) , Emory Functional Ambulatory Profile ( P=.08 ) , and Stroke Impact Scale ( P=.03 ) . In phase 2 , the A-B group maintained improvement in all 3 primary outcomes even without FES . Both groups improved significantly on all primary outcome measures , comparing 6-month to initial measures ( P</=.05 ) . CONCLUSIONS An FES system that stimulates dorsiflexors and plantar flexors similar to the timing of typical adult gait , combined with daily walking , can improve the walking ability of adults with hemiplegia |
12,402 | 29,405,263 | Authors ' conclusions There is insufficient evidence to conclude topical or spatial repellents can prevent malaria . | Abstract Background Malaria is an important cause of illness and death across endemic regions .
Considerable success against malaria has been achieved within the past decade mainly through long‐lasting insecticide‐treated nets ( LLINs ) .
However , elimination of the disease is proving difficult as current control methods do not protect against mosquitoes biting outdoors and when people are active .
Repellents may provide a personal protection solution during these times .
Objectives To assess the impact of topical repellents , insecticide‐treated clothing , and spatial repellents on malaria transmission .
Insecticide‐treated clothing Insecticide‐treated clothing were investigated in trials conducted in refugee camps in Pakistan and amongst military based in the Colombian Amazon . | BACKGROUND Although effective topical repellents provide personal protection against malaria , whether mass use of topical repellents in addition to long-lasting insecticidal nets can contribute to a further decline of malaria is not known , particularly in areas where outdoor transmission occurs . We aim ed to assess the epidemiological efficacy of a highly effective topical repellent in addition to long-lasting insecticidal nets in reducing malaria prevalence in this setting . METHODS A cluster r and omised controlled trial was done in the 117 most endemic villages in Ratanakiri province , Cambodia , to assess the efficacy of topical repellents in addition to long-lasting insecticidal nets in controlling malaria in a low-endemic setting . We did a pre-trial assessment of village accessibility and excluded four villages because of their inaccessibility during the rainy season . Another 25 villages were grouped because of their proximity to each other , result ing in 98 study clusters ( comprising either a single village or multiple neighbouring villages ) . Clusters were r and omly assigned ( 1:1 ) to either a control ( long-lasting insecticidal nets ) or intervention ( long-lasting insecticidal nets plus topical repellent ) study group after a restricted r and omisation . All clusters received one long-lasting insecticidal net per individual , whereas those in the intervention group also received safe and effective topical repellents ( picaridin KBR3023 , SC Johnson , Racine , WI , USA ) , along with instruction and promotion of its daily use . Cross-sectional surveys of 65 r and omly selected individuals per cluster were done at the beginning and end of the malaria transmission season in 2012 and 2013 . The primary outcome was Plasmodium species-specific prevalence in participants obtained by real-time PCR , assessed in the intention-to-treat population . Complete safety analysis data will be published seperately ; any ad-hoc adverse events are reported here . This trial is registered with Clinical Trials.gov , number NCT01663831 . FINDINGS Of the 98 clusters that villages were split into , 49 were assigned to the control group and 49 were assigned to the intervention group . Despite having a successful distribution system , the daily use of repellents was suboptimum . No post-intervention differences in PCR plasmodium prevalence were observed between study groups in 2012 ( 4·91 % in the control group vs 4·86 % in the intervention group ; adjusted odds ratio [ aOR ] 1·01 [ 95 % CI 0·60 - 1·70 ] ; p=0·975 ) or in 2013 ( 2·96 % in the control group vs 3·85 % in the intervention group ; aOR 1·31 [ 0·81 - 2·11 ] ; p=0·266 ) . Similar results were obtained according to Plasmodium species ( 1·33 % of participants in the intervention group vs 1·10 % in the intervention group were infected with Plasmodium falciparum ; aOR 0·83 [ 0·44 - 1·56 ] ; p=0·561 ; and 1·85 % in the control group vs 2·67 % in the intervention group were infected with Plasmodium vivax ; aOR 1·51 [ 0·88 - 2·57 ] ; p=0·133 ) . 41 adverse event notifications from nine villages were received , of which 33 were classified as adverse reactions ( 11 of these 33 were cases of repellent abuse through oral ingestion , either accidental or not ) . All participants with adverse reactions fully recovered and 17 were advised to permanently stop using the repellent . INTERPRETATION Mass distribution of highly effective topical repellents in re source -sufficient conditions did not contribute to a further decline in malaria endemicity in a pre-elimination setting in the Greater Mekong subregion . Daily compliance and appropriate use of the repellents remains the main obstacle . FUNDING Bill & Melinda Gates Foundation Background The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports , including many studies identified by their authors as r and omized controlled trials . It has been noticed that these reports mostly present positive results , and their quality and authenticity have consequently been called into question . We investigated the adequacy of r and omization of clinical trials published in recent years in China to determine how many of them met acceptable st and ards for allocating participants to treatment groups . Methods The China National Knowledge Infrastructure electronic data base was search ed for reports of r and omized controlled trials on 20 common diseases published from January 1994 to June 2005 . From this sample , a subset of trials that appeared to have used r and omization methods was selected . Twenty-one investigators trained in the relevant knowledge , communication skills and quality control issues interviewed the original authors of these trials about the participant r and omization methods and related quality -control features of their trials . Results From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure data base , we found 3137 apparent r and omized controlled trials . Of these , 1452 were studies of conventional medicine ( published in 411 journals ) and 1685 were studies of traditional Chinese medicine ( published in 352 journals ) . Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for r and omization and could on those grounds be deemed authentic r and omized controlled trials ( 6.8 % , 95 % confidence interval 5.9–7.7 ) . There was no statistically significant difference in the rate of authenticity between r and omized controlled trials of traditional interventions and those of conventional interventions . R and omized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals ( relative risk 1.58 , 95 % confidence interval 1.18–2.13 , and relative risk 14.42 , 95 % confidence interval 9.40–22.10 , respectively ) . The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals ( relative risk 9.32 , 95 % confidence interval 5.83–14.89 ) . All r and omized controlled trials of pre-market drug clinical trial were authentic by our criteria . Of the trials conducted at university-affiliated hospitals , 56.3 % were authentic ( 95 % confidence interval 32.0–81.0 ) . Conclusion Most reports of r and omized controlled trials published in some Chinese journals lacked an adequate description of r and omization . Similarly , most so called ' r and omized controlled trials ' were not real r and omized controlled trials owing toa lack of adequate underst and ing on the part of the authors of rigorous clinical trial design . All r and omized controlled trials of pre-market drug clinical trial included in this research were authentic . R and omized controlled trials conducted by authors in high level hospitals , especially in hospitals affiliated to medical universities had a higher rate of authenticity . That so many non-r and omized controlled trials were published as r and omized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed A r and omized , double-blinded , placebo-controlled study was conducted to examine the effect of spatial repellent ( SR ) in households at risk of malaria in Indonesia . Following presumptive radical cure for malaria in 180 adult men representing sentinels of new infection in four clusters within two villages , all households were given either metofluthrin or placebo mosquito coils . Weekly blood smear screening and human-l and ing mosquito catches were done throughout the 6 months intervention . Malaria infections occurred in 61 subjects living in placebo households and 31 subjects living in SR coil households , suggesting a 52 % protective effect of SR . Likewise , anopheles indoor human l and ing rates were 32 % lower in homes receiving SR coils . Differences in the malaria attack rate between SR- and placebo-treated homes was significant when not accounting for the effects of clustering . When the analysis was adjusted for intra-cluster correlation , the differences between SR- and placebo-treated homes were not statistically significant . The findings provide evidence of SR public health benefit and support a larger trial statistically powered to detect those effects Background Mosquito vectors of malaria in Southeast Asia readily feed outdoors making malaria control through indoor insecticides such as long-lasting insecticidal nets ( LLINs ) and indoor residual spraying more difficult . Topical insect repellents may be able to protect users from outdoor biting , thereby providing additional protection above the current best practice of LLINs . Methods and Findings A double blind , household r and omised , placebo-controlled trial of insect repellent to reduce malaria was carried out in southern Lao PDR to determine whether the use of repellent and long-lasting insecticidal nets ( LLINs ) could reduce malaria more than LLINs alone . A total of 1,597 households , including 7,979 participants , were recruited in June 2009 and April 2010 . Equal group allocation , stratified by village , was used to r and omise 795 households to a 15 % DEET lotion and the remainder were given a placebo lotion . Participants , field staff and data analysts were blinded to the group assignment until data analysis had been completed . All households received new LLINs . Participants were asked to apply their lotion to exposed skin every evening and sleep under the LLINs each night . Plasmodium falciparum and P. vivax cases were actively identified by monthly rapid diagnostic tests . Intention to treat analysis found no effect from the use of repellent on malaria incidence ( hazard ratio : 1.00 , 95 % CI : 0.99–1.01 , p = 0.868 ) . A higher socio-economic score was found to significantly decrease malaria risk ( hazard ratio : 0.72 , 95 % CI : 0.58–0.90 , p = 0.004 ) . Women were also found to have a reduced risk of infection ( hazard ratio : 0.59 , 95 % CI : 0.37–0.92 , p = 0.020 ) . According to protocol analysis which excluded participants using the lotions less than 90 % of the time found similar results with no effect from the use of repellent . Conclusions This r and omised controlled trial suggests that topical repellents are not a suitable intervention in addition to LLINs against malaria amongst agricultural population s in southern Lao PDR . These results are also likely to be applicable to much of the Greater Mekong Sub-region . Trial Registration This trial is registered with number We determined the efficacy of the use of permethrin-impregnated uniforms for prevention of malaria and leishmaniasis in a double-blind , r and omized study of Colombian soldiers on patrol . In the study of malaria , soldiers were issued impregnated uniforms ( i.e. , a shirt , an undershirt , pants , socks , and a hat ) or uniforms washed in water ; the soldiers wore the uniforms day and night for a mean of 4.2 weeks and were observed for an additional 4 weeks . Three ( 3 % ) of 86 soldiers wearing impregnated uniforms contracted malaria , whereas 12 ( 14 % ) of 86 soldiers wearing control uniforms contracted malaria ( P = .015 ) . In the study of leishmaniasis ( soldiers were in the area of endemicity for 6.6 weeks and were observed for 12 weeks thereafter ) , 4 ( 3 % ) of 143 soldiers wearing impregnated uniforms and 18 ( 12 % ) of 143 soldiers wearing control uniforms acquired disease ( P = .002 ) . In the leishmaniasis study , and presumably in the malaria study , breakthrough infections in the treated group were primarily due to bites in unclothed regions of the body ( face and h and s ) . Permethrin-treated uniforms were virtually nontoxic ( there were only two cases of mild skin irritation among 229 subjects ) , and impregnation is quick and inexpensive . Impregnation of clothing with permethrin is suggested for nonimmune population s who are likely to be exposed to malaria or leishmaniasis over a period of 1 - 2 months Background The study sought to determine the effect of using insecticide-treated clothes ( ITCs ) on personal protection against malaria infection . The specific objectives were to determine the effect of using ITCs on the rate of infection with malaria parasites and the effect on indoor mosquito density . Methods This study was done in Dadaab refugee camps , North Eastern Province Kenya between April and August 2002 , and involved a total of 198 participants , all refugees of Somali origin . The participants were selected through multi-stage cluster sampling . Half of the participants ( treatment group ) had their personal clothes worn on a daily basis ( Diras , Saris , Jalbaab s , Ma'awis and shirts ) and their bedding ( sheets and blankets ) treated with insecticide ( permethrin ) . The other half ( comparison group ) had their clothes treated with placebo ( plain water ) . Indoor mosquito density was determined from twelve households belonging to the participants ; six in the treatment block and six in the comparison block . During pre-test and post-test , laboratory analysis of blood sample s was done , indoor mosquito density determined and question naires administered . Using STATA statistical package , tests for significant difference between the two groups were conducted . Results Use of ITCs reduced both malaria infection rates and indoor mosquito density significantly . The odds of malaria infection in the intervention group were reduced by about 70 percent . The idea of using ITCs for malaria infection control was easily accepted among the refugees and they considered it beneficial . No side effects related to use of the ITCs were observed from the participants . Conclusion The use of ITCs reduces malaria infection rate and has potential as an appropriate method of malaria control . It is recommended , therefore , that this strategy be considered for use among poor communities like slum dwellers and other underprivileged communities , such as street children and refugees , especially during an influx to malaria-prone regions . Further research on cost-effectiveness and sustainability of this strategy is worthwhile Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more A trial to compare the effect of military clothing treated by high-pressure spray with permethrin or placebo on the incidence of malaria in Royal Thai Army troops was conducted in northeastern Thail and . Bioassays of treated clothing using laboratory-reared Anopheles dirus females showed permethrin remained in the treated fabric for up to 90 days . Both permethrin- and placebo-treated uniform shirts provided > 84 % protection from biting An . dirus in laboratory bioassays for the duration of the study . In laboratory tests , knockdown of An . dirus exposed to permethrin-treated cloth fell to < 20 % after 3 h and washes , despite the presence of 28.7 - 59.9 % of the original dose of permethrin . The use of permethrin-treated uniforms without adjunct application of topical repellents did not reduce malaria in Thai troops in an operational setting where incidence during 6 months was as high as 412 cases/1,000 in spite of chemoprophylaxis and use of untreated bednets Background Mosquito coils are the most commonly used household insecticidal product in the world with sales exceeding 50 billion coils , used by two billion people worldwide annually . Despite strong evidence that coils prevent mosquito bites a systematic review concluded that there is no evidence that burning mosquito coils prevents malaria acquisition . Therefore , the current trial was design ed to measure and compare prevention of malaria infection by mosquito coils or long-lasting insecticidal net ( LLIN ) or a combination of the two in Yunnan , China in the Greater Mekong sub-region . Methods A four-arm single blind household-r and omized design was chosen as coils emanate insecticide throughout the household . Households enrolled at baseline were r and omly allocated by the lottery method to one of the four intervention arms : ( i ) nothing , ( ii ) 0.03 % transfluthrin coils alone , ( iii ) deltamethrin long-lasting insecticide treated nets , ( LLINs ) alone or ( iv ) a combination of transfluthrin coils and deltamethrin LLINs . All household members were recruited to the study , with only those households excluded with pregnant or breastfeeding mothers , members with chest complaints or allergies or members that regularly slept away from home . The main outcome of interest was Plasmodium falciparum malaria prevalence detected by rapid diagnostic tests ( RDTs ) during six repeated monthly cross-sectional surveys . The secondary outcome of interest was the effect on Plasmodium vivax prevalence detected in the same way . Results A total of 2,052 households were recruited into the study , comprising 7,341 individuals The odds ratios of testing positive by RDT with P. falciparum or P. vivax were > 75 % lower for all intervention arms compared with the control arm . Coils alone provided 77 % protection ( 95 % CI : 50%-89 % ) , LLINs provided 91 % protection ( 95 % CI : 72%-97 % ) and the combination of coils and LLINs provided 94 % protection ( 95 % CI : 77%-99 % ) against P. falciparum compared with the control arm . There was no statistically significant difference between the protective efficacies of the different interventions . Conclusions This is the first robust clinical evaluation of transfluthrin mosquito coils as a means to reduce malaria and the high degree of infection prevented would indicate they represent a potentially highly effective tool , which could be integrated into larger vector control programmes . Trial registration Clinical Trials.gov Identifier : NCT00442442 , March 2007 Objective To determine the effectiveness in reducing malaria of combining an insect repellent with insecticide treated bed nets compared with the nets alone in an area where vector mosquitoes feed in the early evening . Design A double blind , placebo controlled cluster-r and omised clinical study . Setting Rural villages and peri-urban districts in the Bolivian Amazon . Participants 4008 individuals in 860 households . Interventions All individuals slept under treated nets ; one group also used a plant based insect repellent each evening , a second group used placebo . Main outcome measure Episodes of Plasmodium falciparum or P vivax malaria confirmed by rapid diagnostic test or blood slide , respectively . Results We analysed 15 174 person months at risk and found a highly significant 80 % reduction in episodes of P vivax in the group that used treated nets and repellent ( incidence rate ratio 0.20 , 95 % confidence interval 0.11 to 0.38 , P<0.001 ) . Numbers of P falciparum cases during the study were small and , after adjustment for age , an 82 % protective effect was observed , although this was not significant ( 0.18 , 0.02 to 1.40 , P=0.10 ) . Reported episodes of fever with any cause were reduced by 58 % in the group that used repellent ( 0.42 , 0.31 to 0.56 , P<0.001 ) . Conclusions Insect repellents can provide protection against malaria . In areas where vectors feed in the early evening , effectiveness of treated nets can be significantly increased by using repellent between dusk and bedtime . This has important implication s in malaria vector control programmes outside Africa and shows that the combined use of treated nets and insect repellents , as advocated for most tourists travelling to high risk areas , is fully justified . Registration NCT 00144716 Background A mosquito repellent has the potential to prevent malaria infection , but there has been few studies demonstrating the effectiveness of combining this strategy with the highly effective long-lasting insecticidal nets ( LLINs ) . This study aim ed to determine the effect of combining community-based mosquito repellent with LLINs in the reduction of malaria . Methods A community-based clustered-r and omised trial was conducted in 16 rural villages with 1,235 households in southern Ethiopia between September and December of 2008 . The villages were r and omly assigned to intervention ( mosquito repellent and LLINs , eight villages ) and control ( LLINs alone , eight villages ) groups . Households in the intervention villages received mosquito repellent ( i.e. , Buzz-Off ® petroleum jelly , essential oil blend ) applied every evening . The baseline survey was followed by two follow-up surveys , at one month interval . The primary outcome was detection of Plasmodium falciparum , Plasmodium vivax , or both parasites , through microscopic examination of blood slides . Analysis was by intention to treat . Baseline imbalances and clustering at individual , household and village levels were adjusted using a generalized linear mixed model . Results 3,078 individuals in intervention and 3,004 in control group were enrolled into the study . Compared with the control arm , the combined use of mosquito repellent and LLINs significantly reduced malaria infection of all types over time [ adjusted Odds Ratio ( aOR ) = 0.66 ; 95 % CI = 0.45 - 0.97 ] . Similarly , a substantial reduction in P. falciparum malaria infection during the follow-up surveys was observed in the intervention group ( aOR = 0.53 , 95 % CI = 0.31 - 0.89 ) . The protective efficacy of using mosquito repellent and LLINs against malaria infection of both P. falciparum/P. vivax and P. falciparum was 34 % and 47 % , respectively . Conclusions Daily application of mosquito repellent during the evening followed by the use of LLINs during bedtime at community level has significantly reduced malaria infection . The finding has strong implication particularly in areas where malaria vectors feed mainly in the evening before bedtime . Trial registration Clinical Trials.gov identifier : NCT01160809 Background Long-lasting insecticidal nets ( LLINs ) have limited effect on malaria transmitted outside of sleeping hours . Topical repellents have demonstrated reduction in the incidence of malaria transmitted in the early evening . This study assessed whether 15 % DEET topical repellent used in combination with LLINs can prevent greater malaria transmission than placebo and LLINs , in rural Tanzania . Methods A cluster-r and omized , placebo-controlled trial was conducted between July 2009 and August 2010 in a rural Tanzanian village . Sample size calculation determined that 10 clusters of 47 households with five people/household were needed to observe a 24 % treatment effect at the two-tailed 5 % significance level , with 90 % power , assuming a baseline malaria incidence of one case/person/year . Ten clusters each were r and omly assigned to repellent and control groups by lottery . A total of 4,426 individuals older than six months were enrolled . All households in the village were provided with an LLIN per sleeping space . Repellent and placebo lotion was replaced monthly . The main outcome was rapid diagnostic test (RDT)-confirmed malaria measured by passive case detection ( PCD ) . Incidence rate ratios were estimated from a Poisson model , with adjustment for potential confounders , determined a priori . According-to- protocol approach was used for all primary analyses . Results The placebo group comprised 1972.3 person-years with 68.29 ( 95 % C.I 37.05 - 99.53 ) malaria cases/1,000 person-years . The repellent group comprised 1,952.8 person-years with 60.45 ( 95 % C.I 48.30 - 72.60 ) cases/1,000 person-years , demonstrating a non-significant 11.44 % reduction in malaria incidence rate in this group , ( Wilcoxon rank sum z = 0.529 , p = 0.596 ) . Principal components analysis ( PCA ) of the socio-economic status ( SES ) of the two groups demonstrated that the control group had a higher SES ( Pearson ’s chi square = 13.38 , p = 0.004 ) . Conclusions Lack of an intervention effect was likely a result of lack of statistical power , poor capture of malaria events or bias caused by imbalance in the SES of the two groups . Low malaria transmission during the study period could have masked the intervention effect and a larger study size was needed to increase discriminatory power . Alternatively , topical repellents may have no impact on malaria transmission in this scenario . Design and implementation of repellent intervention studies is discussed . Trial registration The trial was registered IS RCT N92202008 - http://www.controlled-trials.com/IS RCT The safety of daily application of N , N-diethyl-m-toluamide ( DEET ) ( 1.7 g of DEET/day ) in the second and third trimesters of pregnancy was assessed as part of a double-blind , r and omized , therapeutic trial of insect repellents for the prevention of malaria in pregnancy ( n = 897 ) . No adverse neurologic , gastrointestinal , or dermatologic effects were observed for women who applied a median total dose of 214.2 g of DEET per pregnancy ( range = 0 - 345.1 g ) . DEET crossed the placenta and was detected in 8 % ( 95 % confidence interval = 2.6 - 18.2 ) of cord blood sample s from a r and omly selected subgroup of DEET users ( n = 50 ) . No adverse effects on survival , growth , or development at birth , or at one year , were found . This is the first study to document the safety of DEET applied regularly in the second and third trimesters of pregnancy . The results suggest that the risk of DEET accumulating in the fetus is low and that DEET is safe to use in later pregnancy This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Synthetic repellents based on di-ethyl 3-methyl benzamide ( DEET ) are a popular method of obtaining protection from mosquitoes and yet clear evidence for a protective effect against malaria has hitherto never been convincingly demonstrated . A household r and omized trial was undertaken among a study population of 127 families ( 25 % ) in an Afghan refugee village in Pakistan to compare the efficacy of repellent soap ( Mosbar containing 20 % DEET and 0.5 % permethrin ) vs. a placebo lotion . Cases of falciparum and vivax malaria were detected by passive case detection at the camp 's clinic . At the end of the 6 month trial 3.7 % ( 23 of 618 ) of individuals in the Mosbar group had presented with one or more episodes of falciparum malaria compared with 8.9 % ( 47 of 530 ) of the placebo group ( odds ratio 0.44 , 95 % CI 0.25 - 0.76 ) . 16.7 % of the Mosbar group ( 103 of 618 ) presented with vivax malaria compared with 11.7 % ( 62 of 530 ) of the placebo group , and thus no effect was shown against vivax malaria ( odds ratio 1.29 , 95 % CI 0.86 - 1.94 ) . A considerable proportion of individuals ( 22 % ) had presented with vivax malaria during the 7 months leading up to the trial and thus any intervention effect would be partially masked by relapsed infections . The distribution of mosquitoes among households was broadly similar between Mosbar and placebo groups . The repellent was popularly received and very few side-effects were reported . There is a case for giving repellents more prominence in public health as a preventive measure in regions where vectors bite in the early evening or in emergency situations such as epidemics or newly established refugee camps Insecticide-treated mosquito nets ( ITN ) provide excellent protection against malaria ; however , they have a number of shortcomings that are particularly evident in politically unstable countries or countries at war : not everyone at risk can necessarily afford a net , nets may be difficult to obtain or import , nets may not be suitable for migrants or refugees sleeping under tents or plastic shelter . There is a need to develop cheaper , locally appropriate alternatives for the most impoverished and for victims of complex emergencies . Afghan women , in common with many Muslim peoples of Asia , wear a veil or wrap known as a chaddar to cover the head and upper body . This cloth doubles as a sheet at night , when they are used by both sexes . A r and omized controlled trial was undertaken in which 10 % of the families of an Afghan refugee camp ( population 3950 ) in north-western Pakistan had their chaddars and top-sheets treated with permethrin insecticide at a dosage of 1 g/m2 while a further 10 % had their chaddars treated with placebo formulation . Malaria episodes were recorded by passive case detection at the camp 's health centre . From August to November the odds of having a falciparum or vivax malaria episode were reduced by 64 % in children aged 0 - 10 years and by 38 % in refugees aged < 20 years in the group using permethrin-treated chaddars and top-sheets . Incidence in refugees over 20 years of age was not significantly reduced . The cost of the permethrin treatment per person protected ( US$ 0.17 ) was similar to that for treating bednets ( and cost only 10 - 20 % of the price of a new bednet ) . An entomological study simulating real-life conditions indicated that host-seeking mosquitoes were up to 70 % less successful at feeding on men sleeping under treated chaddars and some were killed by the insecticide . Permethrin-treated top-sheets and blankets should provide appropriate and effective protection from malaria in complex emergencies . In Islamic and non-Islamic countries in Asia , treated chaddars and top-sheets should offer a satisfactory solution for the most vulnerable who can not afford treated nets |
12,403 | 28,779,756 | The analysis of the interventions using the ALBD Community Action Model showed that Preparation and Promotion were used much more frequently than Policy and Physical projects .
Conclusion Noted improvements were an increase in use of objective measures .
Lack of theory , weak method ological design and a lack of reliable and valid measurement were observed . | Background Interventions aim ing to promote active school travel ( AST ) are being implemented globally to reverse AST decline .
This systematic literature provides an up date of AST interventions assessing study quality and theory use to examine progress in the field . | Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design OBJECTIVE To determine whether a multicomponent health promotion intervention for Dutch adolescents ( defined as persons between 12 and 14 years of age ) would be successful in influencing body composition and dietary and physical activity behavior in both the short and long terms . DESIGN R and omized controlled trial . SETTING Ten intervention and 8 control prevocational secondary schools . PARTICIPANTS A total of 1108 adolescents ( mean age , 12.7 years ) . Intervention An interdisciplinary program with an adapted curriculum for 11 lessons in biology and physical education and environmental change options . MAIN OUTCOME MEASURES Body height and weight , waist circumference , 4 skinfold thickness measurements , and dietary and physical activity behavior data . RESULTS Multilevel analyses showed that the intervention remained effective in preventing unfavorable increases in important measures of body composition after 20-month follow-up in girls ( biceps skinfold and sum of 4 skinfolds ) and boys ( triceps , biceps , and subscapular skinfolds ) . Consumption of sugar-containing beverages was significantly lower in intervention schools both after intervention ( boys : -287 mL/d ; 95 % confidence interval [ CI ] , -527 to -47 ; girls : -249 ; -400 to -98 ) and at 12-month follow-up ( boys : -233 ; -371 to -95 ; girls : -271 ; -390 to -153 ) . For boys , screen-viewing behavior was significantly lower in the intervention group after 20 months ( -25 min/d ; 95 % CI , -50 to -0.3 ) . No significant intervention effects on consumption of snacks or active commuting to school were found . CONCLUSION The Dutch Obesity Intervention in Teenagers program result ed in beneficial effects on the sum of skinfold thickness measurements in girls and consumption of sugar-containing beverages in both boys and girls in both the short and long terms Background School-based interventions that target prevention of overweight and obesity in children have been tested with mixed results . Thus , successful interventions are still called for . The aim of the present study was to investigate effects of a multicomponent school-based intervention programme targeting physical activity , sedentary and dietary behaviours on anthropometric outcomes . Methods A 20-month intervention was evaluated in a cluster r and omised , controlled study of 1324 11-year-olds . Outcome variables were body mass index ( BMI ) , BMI -for-age z-score ( BMI z ) , waist circumference ( WC ) , waist-to-height ratio ( WTHR ) and weight status ( International Obesity Task Force 's cut-offs ) . Weight , height and WC were measured objective ly ; pubertal status was self-reported and parental education was self-reported by the parents . Intervention effects were determined by one-way analysis of covariance and logistic regression , after checking for clustering effects of school , and moderating effects of gender , pubertal status and parental education . Results Beneficial effects were found for BMI ( p=0.02 ) and BMI z ( p=0.003 ) in girls , but not in boys . While a beneficial effect was found for BMI ( p=0.03 ) in participants of parents reporting a high level of education , a negative effect was found for WTHR in participants with parents reporting a low level of education ( p=0.003 ) . There were no intervention effects for WC and weight status . Conclusions A multicomponent 20-month school-based intervention had a beneficial effect on BMI and BMI z in adolescent girls , but not in boys . Furthermore , children of higher educated parents seemed to benefit more from the intervention , and this needs attention in future interventions to avoid further increase in social inequalities in overweight and obesity Background Although school-based interventions to promote physical activity in adolescents have been suggested in several recent review s , questions have been raised regarding the effects of the strategies and the methodology applied and for whom the interventions are effective . The aim of the present study was to investigate effects of a school-based intervention program : the HEalth in Adolescents ( HEIA ) study , on change in physical activity , and furthermore , to explore whether potential effects varied by gender , weight status , initial physical activity level and parental education level . Methods This was a cluster r and omized controlled 20 month intervention study which included 700 11-year-olds . Main outcome -variable was mean count per minute ( cpm ) derived from ActiGraph accelerometers ( Model 7164/GT1 M ) . Weight and height were measured objective ly . Adolescents reported their pubertal status in a question naire and parents reported their education level on the consent form . Linear mixed models were used to test intervention effects and to account for the clustering effect of sampling by school . Results The present study showed an intervention effect on overall physical activity at the level of p = 0.05 with a net effect of 50 cpm increase from baseline to post intervention in favour of the intervention group ( 95 % CI −0.4 , 100 ) . Subgroup analyses showed that the effect appeared to be more profound among girls ( Est 65 cpm , CI 5 , 124 , p = 0.03 ) and among participants in the low-activity group ( Est 92 cpm , CI 41 , 142 , p < 0.001 ) , as compared to boys and participants in the high-activity group , respectively . Furthermore , the intervention affected physical activity among the normal weight group more positively than among the overweight , and participants with parents having 13–16 years of education more positively than participants with parents having either a lower or higher number of years of education . The intervention seemed to succeed in reducing time spent sedentary among girls but not among boys . Conclusions A comprehensive but feasible , multi-component school-based intervention can affect physical activity patterns in adolescents by increasing overall physical activity . This intervention effect seemed to be more profound in girls than boys , low-active adolescents compared to high-active adolescents , participants with normal weight compared to the overweight , and for participants with parents of middle education level as opposed to those with high and low education levels , respectively . An implementation of the HEIA intervention components in the school system may have a beneficial effect on public health by increasing overall physical activity among adolescents and possibly among girls and low-active adolescents in particular Background To improve effectiveness of future screen behaviour interventions , one needs to know whether an intervention works via the proposed mediating mechanisms and whether the intervention is equally effective among subgroups . Parental regulation is identified as a consistent correlate of screen behaviours , but prospect i ve evidence as well as the mediation role of parental regulation is largely lacking . This study investigated post-intervention main effects on screen behaviours in the HEIA-intervention – a Norwegian school-based multiple-behaviour study , as well as mediation effects of parental regulation by adolescents ’ and parents ’ report . In addition , moderating effects of gender and weight status on the intervention and mediating effects were explored . Methods Participating schools were r and omized to control ( n = 25 ) or intervention ( n = 12 ) condition . Adolescents ( n = 908 Control ; 510 Intervention ) self-reported their weekday and weekend TV-viewing and computer/game-use . Change in adolescents ’ behaviours was targeted through school and parents . Adolescents , mothers ( n = 591 Control ; 244 Interventions ) and fathers ( n = 469 Control ; 199 Intervention ) reported parental regulation of the screen behaviours post-intervention ( at 20 month ) . The product-of-coefficient test using linear regression analysis was conducted to examine main and mediating effects . Results There was no intervention effect on the screen behaviours in the total sample . Gender moderated effect on weekend computer/game-use , while weight status moderated the effect on weekday TV-viewing and computer/game-use . Stratified analyses showed a small favourable intervention effect on weekday TV-viewing among the normal weight . Parental regulation did not mediate change in the screen behaviours . However , stronger parental regulation was associated with less TV-viewing and computer/game-use with effects being conditional on adolescents ’ versus parental reports . Parental regulation of the screen behaviours , primarily by the parental report , was associated with change in the respective behaviours . Conclusion Multiple behaviour intervention may not affect all equally well , and the effect may differ by weight status and gender . In future interventions parents should be encouraged to regulate their adolescents ’ TV-viewing and computer/game-use on both weekdays and weekends as parental regulation was identified as a determinant of these screen behaviours . However , future intervention studies may need to search for more effective intervention strategies targeting parental regulation . Trial registration Current Controlled Trials IS RCT Active commuting to school increases children 's daily physical activity . The built environment is associated with children 's physical activity levels in cross-sectional studies . This study examined the role of the built environment on the outcomes of a " walking school bus " study . Geographical information systems was used to map out and compare the built environments around schools participating in a pilot walking school bus r and omised controlled trial , as well as along school routes . Multi-level modelling was used to determine the built environment attributes associated with the outcomes of active commuting to school and accelerometer-determined moderate-to-vigorous physical activity ( MPVA ) . There were no differences in the surrounding built environments of control ( n = 4 ) and intervention ( n = 4 ) schools participating in the walking school bus study . Among school walking routes , park space was inversely associated with active commuting to school ( β = -0.008 , SE = 0.004 , P = 0.03 ) , while mixed-l and use was positively associated with daily MPVA ( β = 60.0 , SE = 24.3 , P = 0.02 ) . There was effect modification such that high traffic volume and high street connectivity were associated with greater moderate-to-vigorous physical activity . The results of this study suggest that the built environment may play a role in active school commuting outcomes and daily physical activity Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field Background and purpose : The lack of effective school-based interventions for preventing obesity in children has caused a call for longer duration of interventions and better reporting on design and evaluation methodology . The purpose of this paper is to present the development of the intervention , the design of the effectiveness study , and the test-retest reliability of the main outcome measures in the HEalth In Adolescents ( HEIA ) study . Methods / design : The HEIA intervention programme was developed based on literature review s , a social ecological framework , and focus groups . The intervention aim ed to increase total physical activity ( PA ) and consumption of fruit and vegetables and to decrease screen time and consumption of sugar-sweetened beverages . The intervention programme consisted of a classroom component , including dietary behaviour lessons , computer tailoring , fruit/vegetable and PA breaks , and posters , and an environmental component including active transport campaigns , equipment , suggestions for easy improvements of schoolyards , inspirational courses for teachers ( all with regards to PA ) , and fact sheets to parents . The effect of the intervention programme is evaluated in a cluster r and omised controlled trial design ( intervention = 12 schools , control = 25 schools ) including process evaluation . Main outcomes include anthropometry , PA , screen time , and consumption of fruit , vegetables , and sugar-sweetened beverages . A 2-week test— retest study was conducted among 114 pupils . Determinants of the behaviours were assessed . Similar data were collected from parents . Children ’s PA was measured objective ly by accelerometers . Conclusions : The HEIA study represents a theoretically informed r and omised trial comprising a comprehensive set of multilevel intervention components with a thorough evaluation using reliable outcome measures . The study will contribute to a better underst and ing of determinants of healthy weight development among young people and how such determinants can be modified The annual distance walked by children has fallen 28 % since 1972 , partly because car travel has replaced walking on many school journeys.1 Increasing car use has been linked with obesity , adverse health effects in later life , limitations on children 's independence , traffic congestion , and pollution . 2 3 To inform the development of strategies to reduce school related car travel , we surveyed the travel patterns of urban primary school children . The survey was conducted in the inner London boroughs of Camden and Islington . The question naire — based partly on published surveys 4 5 and prepared in English , Bengali , Turkish , Greek , and Cantonese ( first language s of 85 % of eligible pupils)—asked about that day 's school journey , children 's independent travel , and parental concerns . From the sampling frame of all primary schools ( excluding pilot , boarding , and special schools ) , 31 of the 100 eligible schools were r and omly selected . We weighted sampling probability by combined class sizes in year 2 ( ages 6 - 7 years ) and year Background The evidence -based Dutch Obesity Intervention in Teenagers ( DOiT ) program is a school-based obesity prevention program for 12 to 14-year olds attending the first two years of prevocational education . This paper describes the study protocol applied to evaluate ( a ) the nationwide dissemination process of DOiT in the Netherl and s , and ( b ) the relationship between quality of implementation and effectiveness during nationwide dissemination of the program in the Netherl and s. Methods In order to explore facilitating factors and barriers for dissemination of DOiT , we monitored the process of adoption , implementation and continuation of the DOiT program among 20 prevocational schools in the Netherl and s. The study was an observational study using qualitative ( i.e. semi-structured interviews ) and quantitative methods ( i.e. question naires and logbooks ) . Eight process indicators were assessed : recruitment , context , reach , dosage , fidelity , satisfaction , effectiveness and continuation . All teachers , students and parents involved in the implementation of the program were invited to participate in the study . As part of the process evaluation , a cluster-controlled trial with ten control schools was conducted to evaluate the effectiveness of the program on students ’ anthropometry and energy balance-related behaviours and its association with quality of implementation . Discussion The identified impeding and facilitating factors will contribute to an adjusted strategy promoting adoption , implementation and continuation of the DOiT program to ensure optimal use and , thereby , prevention of obesity in Dutch adolescents . Trial registration Current Controlled Trials IS RCT N92755979 Background Only limited data are available on the development , implementation , and evaluation processes of weight gain prevention programs in adolescents . To be able to learn from successes and failures of such interventions , integral written and published reports are needed . Methods Applying the Intervention Mapping ( IM ) protocol , this paper describes the development , implementation , and evaluation of the Dutch Obesity Intervention in Teenagers ( DOiT ) , a school-based intervention program aim ed at the prevention of excessive weight gain . The intervention focussed on the following health behaviours : ( 1 ) reduction of the consumption of sugar-sweetened beverages , ( 2 ) reduction of energy intake derived from snacks , ( 3 ) decrease of levels of sedentary behaviour , and ( 4 ) increase of levels of physical activity ( i.e. active transport behaviour and sports participation).The intervention program consisted of an individual classroom-based component ( i.e. an educational program , covering 11 lessons of both biology and physical education classes ) , and an environmental component ( i.e. encouraging and supporting changes at the school canteens , as well as offering additional physical education classes).We evaluated the effectiveness of the intervention program using a r and omised controlled trial design . We assessed the effects of the intervention on body composition ( primary outcome measure ) , as well as on behaviour , behavioural determinants , and aerobic fitness ( secondary outcome measures ) . Furthermore , we conducted a process evaluation . Discussion The development of the DOiT-intervention result ed in a comprehensive school-based weight gain prevention program , tailored to the needs of Dutch adolescents from low socio-economic background Background There is limited knowledge as to whether obesity prevention interventions are able to produce change in the determinants hypothesized to precede change in energy balance-related behaviors in young people . The aim of this study was to evaluate the effect of a multi-component intervention on a wide range of theoretically informed determinants of physical activity ( PA ) and sedentary behavior ( SB ) . Moderation effects of gender , weight status and parental education level and whether the perceived intervention dose received influenced the effects were also explored . Methods The HEIA study was a 20-month school-based , r and omized controlled trial to promote healthy weight development . In total , 1418 11-year-olds participated at baseline and post-intervention assessment . Enjoyment , self-efficacy , perceived social support from parents , teachers and friends related to PA , perceived parental regulation of TV-viewing and computer/game-use and perceived social inclusion at schools were examined by covariance analyses to assess overall effects and moderation by gender , weight status and parental education , mid-way and post-intervention . Covariance analyses were also used to examine the role of intervention dose received on change in the determinants . Results At mid-way enjoyment ( p = .03 ) , perceived social support from teachers ( p = .003 ) and self-efficacy ( p = .05 ) were higher in the intervention group . Weight status moderated the effect on self-efficacy , with a positive effect observed among the normal weight only . At post-intervention results were sustained for social support from teachers ( p = .001 ) , while a negative effect was found for self-efficacy ( p = .02 ) . Weight status moderated the effect on enjoyment , with reduced enjoyment observed among the overweight . Moderation effects for parental education level were detected for perceived social support from parents and teachers . Finally , positive effects on several determinants were observed among those receiving a high as opposed to a low intervention dose . Conclusion The intervention affected both psychological and social-environmental determinants . Results indicate that social support from teachers might be a potential mediator of PA change , and that overweight adolescents might be in need of specially targeted interventions to avoid reducing their enjoyment of PA . Further studies should continue to assess how intervention effectiveness is influenced by the participants ’ self-reported dose of intervention received Background Most physical activity and nutrition interventions in children focus on the school setting ; however , evidence suggests that children are less active and have greater access to unhealthy food at home . The aim of this pilot study was to examine the efficacy of a compulsory homework programme for increasing physical activity and healthy eating in children . Methods The six-week ' Healthy Homework ' programme and complementary teaching re source was developed under the guidance of an intersectoral steering group . Eight senior classes ( year levels 5 - 6 ) from two diverse Auckl and primary schools were r and omly assigned into intervention and control groups . A total of 97 children ( 57 intervention , 40 control ) aged 9 - 11 years participated in the evaluation of the intervention . Daily step counts were monitored immediately before and after the intervention using sealed multiday memory pedometers . Screen time , sports participation , active transport to and from school , and the consumption of fruits , vegetables , unhealthy foods and drinks were recorded concurrently in a 4-day food and activity diary . Results Healthy Homework result ed in a significant intervention effect of 2,830 steps.day-1 ( 95 % CI : 560 , 5,300 , P = 0.013 ) . This effect was consistent between sexes , schools , and day types ( weekdays and weekend days ) . In addition , significant intervention effects were observed for vegetable consumption ( 0.83 servings.day-1 , 95 % CI : 0.24 , 1.43 , P = 0.007 ) and unhealthy food consumption ( -0.56 servings.day-1 , 95 % CI : -1.05 , -0.07 , P = 0.027 ) on weekends but not weekdays , with no interactions with sex or school . Effects for all other variables were not statistically significant regardless of day type . Conclusions Compulsory health-related homework appears to be an effective approach for increasing physical activity and improving vegetable and unhealthy food consumption in children . Further research in a larger study is required to confirm these initial results OBJECTIVE To prospect ively examine potential benefits of active commuting to school on measures of weight status and physical activity in a sample of youth . RESEARCH METHODS AND PROCEDURES A cohort of students from seven elementary schools was measured four times -- in the fall and spring of fourth grade ( N = 1083 ) and fifth grade ( N = 924 ) . Participants were classified as active ( walking , biking , or skateboarding to school almost every day for baseline analyses or at least 2 d/wk for analyses of consistent active commuting ) or non-active commuters to school . Accelerometers were used to measure physical activity . Height , weight , and skinfolds were objective ly assessed . RESULTS Boys who actively commuted to school had lower BMI ( p < 0.01 ) and skinfolds ( p < 0.05 ) than non-active commuters to school in the fourth grade . Active commuting to school over 2 years was not associated with BMI change or overweight status . DISCUSSION Walking and cycling to school may contribute to preventing excessive weight gain , or leaner children may walk or cycle to school BACKGROUND As wearable sensors/devices become increasingly popular to promote physical activity ( PA ) , research is needed to examine how and which components of these devices people use to increase their PA levels . AIMS ( 1 ) To assess usability and level of engagement with the Fitbit One and daily SMS-based prompts in a 6-week PA intervention , and ( 2 ) to examine whether use/ level of engagement with specific intervention components were associated with PA change . METHODS Data were analyzed from a r and omized controlled trial that compared ( 1 ) a wearable sensor/ device ( Fitbit One ) plus SMS-based PA prompts , and ( 2 ) Fitbit One only , among overweight/ obese adults ( N = 67 ) . We calculated average scores from Likert-type response items that assessed usability and level of engagement with device features ( e.g. , tracker , website , mobile app , and SMS-based prompts ) , and assessed whether such factors were associated with change in steps/day ( using Actigraph GT3X+ ) . RESULTS Participants reported the Fitbit One was easy to use and the tracker helped to be more active . Those who used the Fitbit mobile app ( 36 % ) vs. those who did not ( 64 % ) had an increase in steps at 6-week follow-up , even after adjusting for previous web/app use : + 545 steps/ day ( SE = 265 ) vs. -28 steps/ day ( SE = 242 ) ( p = .04 ) . CONCLUSIONS Level of engagement with the Fitbit One , particularly the mobile app , was associated with increased steps . Mobile apps can instantly display summaries of PA performance and could optimize self-regulation to activate change . More research is needed to determine whether such modalities might be cost-effective in future intervention research and practice OBJECTIVE : To evaluate the impact of a “ walking school bus ” program on children 's rates of active commuting to school and physical activity . METHODS : We conducted a pilot cluster r and omized controlled trial among 4th- grade rs from 8 schools in Houston , Texas ( N = 149 ) . R and om allocation to treatment or control conditions was at the school level . Study staff walked with children to and from school up to 5 days/week . Outcomes were measured the week before ( time 1 ) and during weeks 4 and 5 of the intervention ( time 2 ) . The main outcome was the weekly rate of active commuting , and a secondary outcome was moderate-to-vigorous physical activity . Covariates included sociodemographics , distance from home to school , neighborhood safety , child BMI z score , parent self-efficacy/ outcome expectations , and child self-efficacy for active commuting . A mixed-model repeated measures regression accounted for clustering by school , and stepwise procedures with backward elimination of nonsignificant covariates were used to identify significant predictors . RESULTS : Intervention children increased active commuting ( mean ± SD ) from 23.8 % ± 9.2 % ( time 1 ) to 54 % ± 9.2 % ( time 2 ) , whereas control subjects decreased from 40.2 % ± 8.9 % ( time 1 ) to 32.6 % ± 8.9 % ( time 2 ) ( P < .0001 ) . Intervention children increased their minutes of daily moderate-to-vigorous physical activity from 46.6 ± 4.5 ( time 1 ) to 48.8 ± 4.5 ( time 2 ) , whereas control children decreased from 46.1 ± 4.3 ( time 1 ) to 41.3 ± 4.3 ( time 2 ) ( P = .029 ) . CONCLUSIONS : The program improved children 's active commuting to school and daily moderate-to-vigorous physical activity Background Rheumatoid arthritis ( RA ) is chronic systematic disease that affects people during the most productive period of their lives . Web-based health interventions have been effective in many studies ; however , there is little evidence and few studies showing the effectiveness of online social support and especially gamification on patients ’ behavioral and health outcomes . Objective The aim of this study was to look into the effects of a Web-based intervention that included online social support features and gamification on physical activity , health care utilization , medication overuse , empowerment , and RA knowledge of RA patients . The effect of gamification on website use was also investigated . Methods We conducted a 5-arm parallel r and omized controlled trial for RA patients in Ticino ( Italian-speaking part of Switzerl and ) . A total of 157 patients were recruited through brochures left with physicians and were r and omly allocated to 1 of 4 experimental conditions with different types of access to online social support and gamification features and a control group that had no access to the website . Data were collected at 3 time points through question naires at baseline , posttest 2 months later , and at follow-up after another 2 months . Primary outcomes were physical activity , health care utilization , and medication overuse ; secondary outcomes included empowerment and RA knowledge . All outcomes were self-reported . Intention-to-treat analysis was followed and multilevel linear mixed models were used to study the change of outcomes over time . Results The best-fit multilevel models ( growth curve models ) that described the change in the primary outcomes over the course of the intervention included time and empowerment as time-variant predictors . The growth curve analyses of experimental conditions were compared to the control group . Physical activity increased over time for patients having access to social support sections plus gaming ( unst and ardized beta coefficient [B]=3.39 , P=.02 ) . Health care utilization showed a significant decrease for patients accessing social support features ( B=–0.41 , P=.01 ) and patients accessing both social support features and gaming ( B=–0.33 , P=.03 ) . Patients who had access to either social support sections or the gaming experience of the website gained more empowerment ( B=2.59 , P=.03 ; B=2.29 , P=.05 ; respectively ) . Patients who were offered a gamified experience used the website more often than the ones without gaming ( t 91=–2.41 , P=.02 ; U=812 , P=.02 ) . Conclusions The Web-based intervention had a positive impact ( more desirable outcomes ) on intervention groups compared to the control group . Social support sections on the website decreased health care utilization and medication overuse and increased empowerment . Gamification alone or with social support increased physical activity and empowerment and decreased health care utilization . This study provides evidence demonstrating the potential positive effect of gamification and online social support on health and behavioral outcomes . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 57366516 ; http://www.controlled-trials . com/IS RCT N57366516 ( Archived by webcite at http://www.webcitation.org/6PBvvAvvV ) R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community Background Community-based interventions are needed to reduce the burden of childhood obesity . Purpose To evaluate the impact of a multi-level promotora-based ( Community Health Advisor ) intervention to promote healthy eating and physical activity and prevent excess weight gain among Latino children . Methods Thirteen elementary schools were r and omized to one of four intervention conditions : individual/family level ( Family-only ) , school/community level ( Community-only ) , combined ( Family + Community ) , or a measurement-only condition . Participants were 808 Latino parents and their children enrolled in kindergarten through 2nd grade . Measures included parent and child body mass index ( BMI ) and a self-administered parent survey that assessed several parent and child behaviors . Results There were no significant intervention effects on children ’s BMI z-score . The family intervention changed several obesity-related child behaviors ( e.g. , fruit/vegetable consumption ) and these were mediated by changes in parenting variables ( e.g. , parent monitoring ) . Conclusion A promotora-based behavioral intervention was efficacious at changing parental factors and child obesity-related health behaviors |
12,404 | 29,543,325 | Likewise , magnesium aspartate decreased the proportion of participants discontinuing benzodiazepines ( 1 study , 144 participants ; RR 0.80 , 95 % CI 0.66 to 0.96 ; NNTH 5.8 ; very low- quality evidence ) .Generally , adverse events were insufficiently reported .
AUTHORS ' CONCLUSIONS Given the low or very low quality of the evidence for the reported outcomes , and the small number of trials identified with a limited number of participants for each comparison , it is not possible to draw firm conclusions regarding pharmacological interventions to facilitate benzodiazepine discontinuation in chronic benzodiazepine users . | BACKGROUND Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use .
Benzodiazepines are used by approximately 4 % of the general population , with increased prevalence in psychiatric population s and the elderly .
After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence .
This review investigated if pharmacological interventions can facilitate benzodiazepine tapering .
OBJECTIVES To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use . | PURPOSE To evaluate the effectiveness and tolerability of pregabalin in the management of the discontinuation of benzodiazepines in long-term users . SUBJECTS AND METHODS We performed a 12-week , prospect i ve , uncontrolled , non-interventional , and observational study in patients aged 18 years old or above , who met DSM-IV-TR criteria for benzodiazepine dependence without other major psychiatry disorder . Evaluations included the Benzodiazepine Withdrawal Symptom Question naire , the Hamilton Anxiety Rating Scale , the Clinical Global Impression Scale , and the Sheehan Disability Scale . A urine drug screen for benzodiazepines was performed at baseline and every 4 weeks thereafter . The primary effectiveness variable was success rate , defined as achievement of benzodiazepine-free status at week 12 according to the urine drug screen . RESULTS AND DISCUSSION The mean dose at week 12 was 315 ( ±166 ) mg/day . The success rate of the benzodiazepine taper in the primary efficacy population ( n=282 ) was 52 % ( 95 % confidence interval [ CI ] , 46 - 58 ) . Success rates for women and men were 58 % ( 95 % CI , 49 - 67 ) and 46 % ( 95 % CI , 38 - 55 ) , respectively . The success rates did not differ according to either the benzodiazepine of abuse or the presence of other substance use disorders . Significant and clinical ly relevant improvements were observed in withdrawal and anxiety symptoms , as well as in patients ' functioning . At week 12 , tolerability was rated as good or excellent by 90 % and 83 % of the clinicians and patients , respectively . CONCLUSION Our results suggest that pregabalin is an efficacious and well-tolerated adjunctive treatment for benzodiazepine withdrawal Chronic normal-dose benzodiazepine users requesting drug withdrawal were allocated to substitution with either the new anxiolytic alpidem ( n = 13 ) or placebo ( n = 12 ) . During the first 2 weeks of the tapering programme , the dose of benzodiazepine was kept constant ; for the next 2 weeks it was halved and half-dose alpidem ( 25 mg twice daily ) or placebo substituted ; for weeks 5 and 6 , the benzodiazepine was discontinued and full-dose alpidem or placebo given ; next alpidem or placebo were tapered to half-dose and then finally discontinued . Regular anxiety and tranquillizer withdrawal ratings were made . Nine of 12 patients given placebo withdrew successfully compared with four of 13 alpidem-treated patients . Anxiety and other symptom levels increased in the alpidem but not the placebo patients . It was concluded that alpidem is not helpful in helping patients withdrawing from a benzodiazepine withdrawal perhaps because of partial agonist properties . These actions may imply a lesser propensity to induce dependence on long-term use Abstract Twenty-four volunteers ( 19 women and five men ) with insomnia and a history of chronic use of benzodiazepine hypnotics participated in a r and omized , double blind , controlled clinical trial . The study was design ed to assess the effects of substituting zopiclone ( ZOP ) – as an hypnotic – among chronic users of flunitrazepam ( FLU ) , and to compare the subsequent withdrawal of ZOP with placebo controlled withdrawal of FLU . During the 5 weeks of a withdrawal protocol , sleep and physiological parameters were assessed by polysomnographic measures for 11 nights and by nightly actigraphic recordings for weeks 1 , 3 , and 5 . Subjective effects of the withdrawal process were evaluated with daily sleep diaries , and with various weekly self-report symptom checklists . Paired t-tests performed on differences in objective sleep parameters between baseline and the last weeks of the withdrawal program showed a significant decrease in sleep quality within the FLU group , but not in the ZOP group . Subjective sleep diaries consistently reflected the objective ly measured changes in sleep throughout the withdrawal program , indicating significant changes in sleep parameters only in the FLU group . The results obtained from the self report inventories aim ed at assessing withdrawal symptoms , however , revealed no differences between the baseline week and the termination week of the program in any of the groups . After completing the pharmacological withdrawal , all subjects received a short-term cognitive behavioral intervention focused on improving their coping strategies with symptoms of insomnia ; they were evaluated immediately after concluding the intervention , and at 3 and 12 month follow-ups Objective To evaluate the association between use of benzodiazepines and incident dementia . Design Prospect i ve , population based study . Setting PAQUID study , France . Participants 1063 men and women ( mean age 78.2 years ) who were free of dementia and did not start taking benzodiazepines until at least the third year of follow-up . Main outcome measures Incident dementia , confirmed by a neurologist . Results During a 15 year follow-up , 253 incident cases of dementia were confirmed . New use of benzodiazepines was associated with an increased risk of dementia ( multivariable adjusted hazard ratio 1.60 , 95 % confidence interval 1.08 to 2.38 ) . Sensitivity analysis considering the existence of depressive symptoms showed a similar association ( hazard ratio 1.62 , 1.08 to 2.43 ) . A secondary analysis pooled cohorts of participants who started benzodiazepines during follow-up and evaluated the association with incident dementia . The pooled hazard ratio across the five cohorts of new benzodiazepine users was 1.46 ( 1.10 to 1.94 ) . Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50 % increase in the risk of dementia ( adjusted odds ratio 1.55 , 1.24 to 1.95 ) compared with never users . The results were similar in past users ( odds ratio 1.56 , 1.23 to 1.98 ) and recent users ( 1.48 , 0.83 to 2.63 ) but reached significance only for past users . Conclusions In this prospect i ve population based study , new use of benzodiazepines was associated with increased risk of dementia . The result was robust in pooled analyses across cohorts of new users of benzodiazepines throughout the study and in a complementary case-control study . Considering the extent to which benzodiazepines are prescribed and the number of potential adverse effects of this drug class in the general population , indiscriminate widespread use should be caution ed against Withdrawal from hypnotics can produce a variety of problems , especially sleep difficulties , some of which may arise from the multiple actions of most hypnotics , thus producing a range of rebound effects . This study examined whether switching patients to a hypnotic with a narrower range of action and of a different class would reduce these problems . One hundred and thirty-four patients participated ; they were r and omly allocated to one of three methods of switching from " previous hypnotic " to zopiclone ( a cyclopyrrolone ) . The methods were gap ( an interval between taking the two drugs ) ; abuttal ( taking zopiclone immediately on stopping previous drug ) ; and overlap ( gradually reducing previous drug after starting zopiclone ) . The main findings were that zopiclone was associated with better sleep and increased alertness ; the abuttal method was the best method of switching ; and no serious side effects from zopiclone were reported . It was concluded that zopiclone has a useful role in benzodiazepine withdrawal , and that immediate substitution is the best method ABSTRACT Background : Benzodiazepine use disorders are a common clinical problem among methadone maintenance treatment patients and have adverse effects on clinical outcomes . Objectives : To evaluate gabapentin for the outpatient treatment of benzodiazepine abuse or dependence in methadone maintenance patients . Methods : Participants ( n = 19 ) using benzodiazepines at least 4 days per week were enrolled into an 8-week r and omized double-blind placebo-controlled outpatient pilot trial . All participants received a manual-guided supportive psychotherapy aim ed to promote abstinence . Study medication was titrated over a 2-week period to a maximum dose of gabapentin 1200 mg or placebo three times a day . Benzodiazepine use was assessed using urine toxicology confirmed self-report . Benzodiazepines were not provided as part of study participation ; participants were provided guidance to gradually reduce benzodiazepine intake . Results : Sixteen participants had post-r and omization data for analysis . Retention at week eight was 50 % . The mean dose of gabapentin achieved by titration was 2666 mg/day ( SD = ± 1446 ) . There were no significant between group differences on benzodiazepine use outcomes ( amount benzodiazepine per day [ Mann-Whitney U = 27 , p = 0.745 ] , abstinent days per week [ U = 28 , p = 0.811 ] ) and Clinical Instrument Withdrawal Assessment (CIWA)-benzodiazepines scale ( U = 29.0 , p = 0.913 ) . One participant in the gabapentin group discontinued study medication because of peripheral edema . Two participants in the placebo group requested admission for inpatient detoxification treatment . Conclusion : In outpatient methadone-maintained patients with benzodiazepine use disorder , gabapentin did significantly decrease benzodiazepine use relative to placebo . The small sample recruited for this trial may have limited the ability to detect a group difference Ten long-term users of benzodiazepines ( average daily dose , 20 mg of diazepam or equivalent ) who had experienced problems in withdrawing from the drugs were given an i.v . challenge with either the benzodiazepine antagonist flumazenil ( 1 mg injected over 30 s ) or placebo ( vehicle solution ) in a r and omized double-blind design . There were no ' pseudo withdrawal ' responses to either single-blind or double-blind placebo injections , whereas flumazenil produced dramatic panic reactions in all four subjects tested , followed by characteristic benzodiazepine withdrawal symptoms . There were also small but significant rises in pulse rate and blood pressure , but no change in serum cortisol . Flumazenil-induced panic could not be entirely accounted for by a past or present diagnosis of panic disorder , and did not seem to be related to previous withdrawal problems , present benzodiazepine dosage , or to the severity of withdrawal symptoms precipitated by flumazenil in the same challenge test . Attempts to reduce benzodiazepine intake over the next 3 weeks tended to be more successful in the flumazenil group . The results are discussed with reference to possible changes in the GABA-benzodiazepine system in long-term benzodiazepine users Objectives . We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder . Methods . R and omised , placebo-controlled , blinded , parallel superiority trial of 24 weeks duration . Participants were r and omised to prolonged-release melatonin 2 mg daily versus matching placebo and were continuously guided to gradually reduce their usual benzodiazepine dosage . The primary outcome was mean benzodiazepine daily dosage at 24 weeks . Secondary outcomes included pattern of benzodiazepine dosage over time , benzodiazepine cessation proportion , and benzodiazepine withdrawal symptoms . Results . In total , 86 patients ( 21–74 years ) were enrolled : 42 were r and omised to melatonin versus 44 to placebo . We found no significant effect of melatonin on mean benzodiazepine dosage at 24 weeks ( melatonin group 8.01 mg versus placebo group 5.72 mg diazepam equivalents ; difference between means –2.29 ; 95 % CI –5.78 to 1.21 ; P = 0.20 ) . Benzodiazepine cessation proportion was 38.1 % ( 16/42 ) in the melatonin group versus 47.7 % ( 21/44 ) in the placebo group ( OR 0.64 ; 95 % CI 0.26 to 1.56 ; P = 0.32 ) . Prolonged-release melatonin had no effect on benzodiazepine withdrawal symptoms . Conclusions . Benzodiazepine dosage was comparably low between the groups after 24 weeks of guided gradual dose reduction . In this context , prolonged-release melatonin did not seem to further facilitate benzodiazepine discontinuation Since recent research has suggested that the major metabolites of progesterone are barbiturate-like modulators of GABAergic function , we undertook a pilot study of the efficacy of micronized progesterone in attenuating withdrawal and facilitating discontinuation in benzodiazepine-dependent patients with a minimum of 1 year of continuous daily use . Forty-three patients taking a mean daily dose of 16.2 mg of diazepam ( or its equivalent ) were assigned , double-blind , to treatment with either placebo ( n=13 ) or progesterone ( n=30 ) . Progesterone was titrated to a mean daily dose of 1983 mg , and was co-administered for 3 weeks , after which the benzodiazepine was tapered by 25 % per week . Progesterone ( or placebo ) was then continued for 4 weeks before being discontinued . There was no progesterone versus placebo difference in the severity of taper withdrawal . Withdrawal checklist change scores were 17.3 for progesterone and 16.5 for placebo ( F 0.63;df 2,31 ; n.s . ) , and the Hamilton rating scale for anxiety change scores were 7.8 for progesterone and 6.3 for placebo ( F 0.22;df 2,30 ; n.s . ) . There was no difference in ability to remain drug-free at 12 weeks post-taper , with 57 % of progesterone-treated patients , and 58 % of placebo-treated patients having a successful outcome Abstract . Objective : We have previously demonstrated that temporary substitution with a low-dose hypnosedative drug may lead to successful withdrawal from chronic benzodiazepine ( BZD ) use in the majority of patients admitted to a geriatric ward . In the present study , a withdrawal programme was evaluated in which the habitual treatment with BZDs was replaced by either 1 mg lormetazepam or placebo , defining withdrawal success rate , sleep quality and withdrawal symptoms as main outcomes . Methods : The target population was geriatric in patients who had been taking BZDs for at least 3 months . Subjects suffering from mental disorders were excluded . Lormetazepam or placebo were r and omly assigned and given in a double-blind fashion . After 1 week , the replacement therapy was discontinued . Subjective estimations of sleep quality and withdrawal symptoms were registered at predefined intervals , four times in a period of 30 days , using st and ard question naires ( the Pittsburgh Sleep Quality Index and the Benzodiazepine Withdrawal Symptom Question naire , respectively ) . Results : The success rate was significantly higher in the lormetazepam substitution group ( 80 % vs 50 % in the placebo group , P<0.05 ) . Both the subjective quality of sleep and withdrawal symptoms were significantly better in the lormetazepam substitution group . Important withdrawal effects were observed in the control group in two patients with a history of chronic alcohol abuse . Conclusions : Initial replacement therapy with a low-dose BZD is preferred over placebo , since the latter alternative is associated with worse sleep quality and a lower success rate . Placebo must only be used under medical scrutiny , given the potential for unmasking delirious symptoms , especially in patients with concomitant alcoholism Objective : Therapeutic approaches for benzodiazepine ( BZD ) dependence in patients in methadone maintenance treatment ( MMT ) have met with limited success . Clonazepam detoxification ( CDTX ) and clonazepam maintenance treatment ( CMT ) were compared in an open , clinical naturalistic study on such patients . Methods : Benzodiazepine dependent patients substituted their BZD of abuse for clonazepam and were then either detoxified ( CDTX ) or a maintenance dose was reached and maintained ( CMT ) . Patients were considered as failing the trial if they either abused BZDs ( CDTX group ) or abused BZDs over the maintenance dose ( CMT group ) . Treatment outcome was evaluated based upon self and staff reports over 1 year after beginning treatment . Axis I and II psychiatric diagnosis was assessed and methadone dosage and history of abuse was recorded . Results : In the CDTX group , 9/33 ( 27.3 % ) , were BZD-free after 2 months . In the CMT group , 26/33 ( 78.8 % ) refrained from abusing additional BZDs over the maintenance dose after 2 months . The same success rate remained over the entire year . Survival analysis showed CMT to be more successful than the CDTX . Axis I psychiatric comorbidity was found to be positively related to treatment success in the CMT group while axis II antisocial personality disorder was found to be negatively related to treatment success in that group . It had no impact in the CDTX group . Conclusions : Maintenance strategy with clonazepam is a useful BZD treatment modality for BZD-dependent MMT patients with a long-term history of abuse and previous attempts at detoxification . Psychiatric comorbidity may have an important role in choosing the adequate treatment modality and influencing treatment outcome BACKGROUND Many patients with depression take benzodiazepine drugs long term despite the absence of continuing therapeutic value . AIMS To evaluate a treatment programme involving gradual discontinuation with or without simultaneous selective serotonin reuptake inhibitor ( SSRI ) prescribing and to determine the long-term outcome after benzodiazepine withdrawal . METHOD Patients went through three phases - change to an equivalent dose of diazepam ; subsequent r and omisation to either 20 mg of paroxetine or placebo ; and gradual reduction of diazepam in depression-free patients - with a follow-up after 2 or 3 years . RESULTS A total of 230 patients were recruited and 75 % in the paroxetine group and 61 % in the placebo group were successfully treated after 6 weeks ( P:=0.067 ) . After 2 or 3 years 13 % of patients were still benzodiazepine free : 26 % of those who had successfully tapered off benzodiazepine and 6 % of the total group . CONCLUSIONS Transfer to diazepam followed by gradual withdrawal is an effective way of discontinuing chronic benzodiazepine use . The addition of SSRI treatment is of limited value The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Twenty four long-term benzodiazepine users were allocated r and omly to treatment with either buspirone ( mean dose 25 mg/day ) or placebo , prior to tapering off the benzodiazepine over 6 weeks . In both groups , six out of 12 patients successfully completed withdrawal . However , buspirone-treated patients tended to have lower anxiety levels than placebo-treated patients . The amount of previous benzodiazepine usage predicted outcome Abstract Recent uncontrolled research suggested that trazodone and sodium valproate may be helpful in benzodiazepine ( BZ ) discontinuation . We therefore undertook a double-blind study to assess whether trazodone and valproate , as compared to placebo , would attenuate withdrawal and facilitate discontinuation in BZ-dependent patients with a minimum of 1 year daily BZ use . Seventy-eight patients , taking a mean dose of 19 ± 17 mg/day of diazepam ( or its equivalent ) , were stabilized for several weeks on their BZ ( 16 diazepam , 25 lorazepam , 37 alprazolam ) and then for 1–2 weeks , pretreated with trazodone , sodium valproate or placebo before being tapered at 25 % per week . All treatments were continued for 5 weeks post-taper . BZ-free status was assessed after 5 and 12 weeks post-taper . Neither trazodone nor valproate had any significant effect on withdrawal severity . Peak physician withdrawal checklist change from baseline to peak severity was 16.4 for trazodone , 18.04 sodium valproate and 18.24 placebo ( F = 0.10 ; NS ) . Taper success rates were significantly effected by both active agents at the 5-week , but not 12-week , assessment . At 5 weeks post-taper , 79 % of sodium valproate and 67 % of trazodone , but only 31 % of placebo patients were BZ-free ( χ2 = 7.34 ; df 2 ; P < 0.03 ) . Major adverse events for trazodone were sedation and dry mouth , and for valproate , diarrhea , nausea and headaches Background Hypnotics are widely used by the elderly , and their impact on mortality remains controversial . The inconsistent findings could be due to method ological limitations , notably the lack of control for underlying sleep symptoms or illness associated with hypnotic use , for example , insomnia symptoms and excessive daytime sleepiness , depression and anxiety . Our objective was to examine the association between the use of hypnotics and mortality risk in a large cohort of community-dwelling elderly , taking into account a wide range of potential competing risks including sociodemographic characteristics , lifestyle , and chronic disorders as well as underlying psychiatric disorders and sleep complaints . Methods Analyses were carried out on 6,696 participants aged 65 years or older r and omly recruited from three French cities and free of dementia at baseline . Adjusted Cox proportional hazards models with delayed entry , and age of the participants as the time scale , were used to determine the association between hypnotic use and 12-year survival . Results At baseline , 21.7 % of the participants regularly used at least one hypnotic . During follow-up , 1,307 persons died , 480 from cancer and 344 from cardiovascular disease . Analyses adjusted for study center , age and gender showed a significantly greater risk of all-cause and cardiovascular-related mortality with hypnotics , particularly benzodiazepines , and this increased with the number of hypnotics used . None of these associations were significant in models adjusting for sociodemographic and lifestyle characteristics , chronic disorders including cardiovascular pathologies , sleep and psychiatric disorders . Results remained unchanged when duration of past hypnotic intake or persistent versus intermittent use during follow-up were taken into account . Conclusions When controlling for a large range of potential confounders , the risk of mortality was not significantly associated with hypnotic use regardless of the type and duration . Underlying psychiatric disorders appear to be the principal confounders of the observed association Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms Abstract Flumazenil , a partial benzodiazepine agonist with low intrinsic activity , was tested for potential use in patients experiencing withdrawal symptoms after traditional treatment for benzodiazepine dependency . On two occasions , separated by 1–13 weeks , ten patients treated for benzodiazepine dependency and ten controls received cumulative doses of flumazenil ( 0.05 , 0.10 , 0.25 , 0.50 and 1.00 mg at 15-min intervals ) or placebo , with assessment s of withdrawal symptoms and physiological variables after each dose . As expected , there was an overall difference between patients and controls , with patients scoring higher on negative and somatic items and lower on positive psychological items . Flumazenil reduced symptoms thought to be important in withdrawal in patients treated for benzodiazepine dependency . In contrast to the patient group , controls reacted in the opposite direction with increases in negative experience when given flumazenil . Further research may develop flumazenil as a therapeutic option in the treatment of benzodiazepine withdrawal Chronic benzodiazepine use is common in patients with mental illness and is associated with cognitive impairment . It is unclear whether benzodiazepine-induced cognitive impairment is reversible . Amelioration of cognitive dysfunction may be facilitated during benzodiazepine tapering by add-on melatonin due to its anti-inflammatory and neuroprotective properties . We examined how melatonin and benzodiazepine withdrawal affect cognition , subjective well-being , and psychosocial functioning . Eighty patients with schizophrenia or bipolar disorder were r and omized to add-on treatment once daily with either prolonged-release melatonin or placebo in a 24-week , double-blind clinical trial . All participants gradually tapered usual benzodiazepine dosage in a closely monitored treatment setting . We used the Brief Assessment of Cognition in Schizophrenia ( BACS ) to assess neurocognitive performance with additional assessment s of subjective well-being and psychosocial functioning . BACS composite and subscale scores ( except motor speed ) significantly improved in parallel with benzodiazepine dose reduction , but there was no additional effect of melatonin . Cognitive performance was still markedly impaired post-tapering compared with normative data . Neither benzodiazepine withdrawal nor treatment group affected subjective well-being or psychosocial functioning . In conclusion , add-on melatonin does not seem to affect cognition , well-being , or psychosocial functioning in patients with severe mental illness . The observed improvement in cognitive performance could not be distinguished from retest effects , which may in turn have been facilitated by the benzodiazepine tapering Flumazenil ( FLU ) , a benzodiazepine ( BZD ) partial agonist with a weak intrinsic activity , was previously found unable to precipitate withdrawal in tolerant subjects su bmi tted to long‐lasting BZD treatment . The potential use of FLU to treat BZD withdrawal symptoms has also been evaluated tentatively in clinical studies . In the present experiment , FLU ( treatment A ) was compared with oxazepam tapering ( treatment B ) and placebo ( treatment C ) in the control of BZD withdrawal symptoms in three groups of BZD dependent patients . Group A patients ( 20 ) received FLU 1 mg twice a day for 8 days , and oxazepam 30 mg in two divided doses ( 15 mg + 15 mg ) during the first night , oxazepam 15 mg during the second night and oxazepam 7.5 mg during the third night . FLU was injected i.v . in saline for 4 hours in the morning and 4 hours in the afternoon , in association with placebo tablets . Group B patients ( 20 ) were treated by tapering of oxazepam dosage ( from 120 mg ) and with saline solution ( as placebo ) instead of FLU for 8 days . Group C patients ( 10 ) received saline instead of FLU and placebo tablets instead of oxazepam for 8 days . FLU immediately reversed BZD effects on balance task and significantly reduced withdrawal symptoms in comparison with oxazepam and placebo on both self‐reported and observer‐rated withdrawal scales . The partial agonist also reduced craving scores during the detoxification procedure . In addition , during oxazepam tapering , group B patients experienced paradoxical symptoms that were not apparent in FLU patients . Patients treated with FLU showed a significantly lower relapse rates on days 15 , 23 and 30 after the detoxification week . Our data provide further evidence of FLUs ability to counteract BZD effects , control BZD withdrawal and normalize BZD receptor function . The effectiveness of FLU may reflect its capacity to upregulate BZD receptors and to reverse the uncoupling between the recognition sites of BZD and GABA , on the GABA A macromolecular complex , that has been reported in tolerant subjects Buspirone is a new antianxiety compound of a totally new type which may avoid the dependence problems of its predecessors . This study was design ed to evaluate any possible cross-tolerance to the benzodiazepines . Twenty-four out patients on long-term therapeutic dose benzodiazepine treatment , who wished to discontinue treatment , were allocated r and omly to placebo substitution or buspirone substitution and then withdrawal over a total of 10 weeks . Assessment s were made at weekly intervals . Of the 24 patients entered into the trial , 13 received buspirone and 11 placebo . Only five of the buspirone and six of the placebo patients successfully completed withdrawal . Some anxiolytic action of buspirone was detected , but it was insufficient to material ly assist the withdrawal . No evidence was found that buspirone was cross-tolerant to the benzodiazepines . It was concluded that buspirone does not help benzodiazepine withdrawal and does not suppress benzodiazepine withdrawal symptoms Serotonin is implicated in the etiology of anxiety disorders and in the anxiolytic actions of benzodiazepines . Pre clinical studies with 5-HT3 receptor antagonists , including ondansetron , show they have anxiolytic properties and that ondansetron suppresses withdrawal anxiety after abrupt discontinuation of chronic benzodiazepine treatment . We evaluated the efficacy of ondansetron as an adjunctive medication in the discontinuation of benzodiazepines in long-term users . One hundred eight patients who had used alprazolam or lorazepam regularly for > 3 months entered , and 97 completed a r and omized double-blind discontinuation treatment program during which they received either ondansetron 2 mg twice daily or placebo and flexibly tapered their benzodiazepine over a 6-week period . There were no significant differences between the patients who had entered and completed treatment . Three weeks postmedication , 63 % of the patients discontinued use of benzodiazepine . The percentage of reduction of benzodiazepine daily dosage at all time points in the treatment trial was similar for the ondansetron and placebo groups . Ondansetron had no significant effects on severity of withdrawal symptoms or levels of anxiety . High placebo response may have prevented detection of an ondansetron effect . At 1 year follow-up , 68 % of patients reported that they stopped using benzodiazepine . Patient characteristics were more important than ondansetron in tapered benzodiazepine discontinuation Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . BACKGROUND Benzodiazepines are the most frequently used drug for the treatment of insomnia . Prolonged use of benzodiazepine therapy is not recommended . However , many patients , particularly older patients , have difficulties discontinuing therapy . Melatonin , a hormone that is produced at night by the pineal gl and , promotes normal sleep in humans and augments sleep induction by benzodiazepine therapy . OBJECTIVE To assess whether the administration of melatonin could facilitate the discontinuation of benzodiazepine therapy in patients with insomnia . METHODS Thirty-four subjects receiving benzodiazepine therapy were enrolled in the 2-period study . In period 1 , patients received ( double-blinded ) melatonin ( 2 mg in a controlled-release formulation ) or a placebo nightly for 6 weeks . They were encouraged to reduce their benzodiazepine dosage 50 % during week 2 , 75 % during weeks 3 and 4 , and to discontinue benzodiazepine therapy completely during weeks 5 and 6 . In period 2 , melatonin was administered ( single-blinded ) for 6 weeks to all subjects and attempts to discontinue benzodiazepine therapy were resumed . Benzodiazepine consumption and subjective sleep- quality scores were reported daily by all patients . All subjects were then allowed to continue melatonin therapy and follow-up re assessment s were performed 6 months later . RESULTS By the end of period 1 , 14 of 18 subjects who had received melatonin therapy , but only 4 of 16 in the placebo group , discontinued benzodiazepine therapy ( P = .006 ) . Sleep- quality scores were significantly higher in the melatonin therapy group ( P = .04 ) . Six additional subjects in the placebo group discontinued benzodiazepine therapy when given melatonin in period 2 . The 6-month follow-up assessment s revealed that of the 24 patients who discontinued benzodiazepine and received melatonin therapy , 19 maintained good sleep quality . CONCLUSION Controlled-release melatonin may effectively facilitate discontinuation of benzodiazepine therapy while maintaining good sleep quality Cyamemazine is an anxiolytic antipsychotic , which reduces ethanol withdrawal symptoms . Here , we investigated if cyamemazine can be also effective as substitute drug to facilitate benzodiazepine withdrawal . A total of 168 patients treated with benzodiazepines for at least 3 months and with a < 18 score in the Hamilton Anxiety Rating Scale ( HARS ) were included in the study . Previous benzodiazepine treatment was withdrawn , and patients were r and omized to a 4-week treatment with cyamemazine ( 25 - 50 mg q.d . ) or bromazepam ( 3 - 6 mg q.d . ) , followed by 2 weeks of placebo . The primary efficacy variable was the maximal anxiety rebound as measured with the HARS during the 42 days of treatment . No statistically significant differences between treatment groups were found for the extent or incidence of rebound anxiety . Considering all dropout patients as withdrawal failures , after 6 months of follow-up , 56/84 patients in the cyamemazine group ( 66.7 % ) and 55/84 patients in the bromazepam group ( 65.5 % ) were successfully withdrawn . 28 patients in the cyamemazine group and 18 in the bromazepam group had an adverse event , including anxiety , insomnia , dry mouth and somnolence . No extra-pyramidal symptoms were reported . In conclusion , cyamemazine was comparable to bromazepam in ensuring successful benzodiazepine withdrawal and in controlling the acute benzodiazepine withdrawal syndrome . Cyamemazine may be useful to facilitate benzodiazepine withdrawal in those patients where bromazepam substitution is not appropriate 40 patients seen in general practice and psychiatric outpatient clinics who had taken lorazepam or diazepam alone in regular dosage for a mean period of 3.6 years had their benzodiazepine replaced by propranolol ( 60 - -120 mg/day ) or placebo for two weeks under double-blind conditions . Depending on the criteria for the definition of an abstinence syndrome , 27 - -45 % of the patients had withdrawal symptoms during the study . Propranolol did not affect the drop-out rate or the incidence of withdrawal symptoms but significantly reduced their severity in patients completing the study . The percentage fall in serum levels of desmethyldiazepam in patients who experienced withdrawal symptoms after stopping diazepam was significantly greater in patients with no withdrawal symptoms BACKGROUND The possibility that treatment with tricyclic antidepressants , in the form of dothiepin , might attenuate benzodiazepine withdrawal symptoms was investigated in a double-blind trial . METHOD Eighty-seven non-depressed psychiatric out- patients with putative normal dose benzodiazepine dependence had their benzodiazepines reduced in stepwise amounts of 20 % of the original dose for eight weeks . The patients were r and omised to receive dothiepin ( with dosage increasing to 150 mg/day ) or placebo as an aid to withdrawal before benzodiazepine reduction and these drugs were taken for four further weeks before being stopped . RESULTS Fewer patients entered and completed the study than expected and a Type II error was possible in the results . Although there was some evidence of withdrawal symptoms being less marked in those patients allocated to dothiepin this was independent of any antidepressant effect as depression scores were lower in the placebo group in the early phase of withdrawal ( P < 0.01 ) . Of those completing the study , greater satisfaction ( P = 0.03 ) was recorded by those who had received dothiepin ; no other differences reached statistical significance . CONCLUSIONS Dothiepin ( and by implication other tricyclic antidepressants ) might have some value in reducing benzodiazepine withdrawal symptoms but does not aid drug withdrawal Background Benzodiazepine use is widespread in older people , although its benefit is uncertain . Aim To investigate the long-term effect of benzodiazepine use upon dementia risk . Methods A prospect i ve cohort of men seen on five occasions over 22 years with full medication histories , repeat measures of cognitive function and a clinical diagnosis of dementia . Results Of 1134 men with complete data , 103 ( 9.1 % ) had been taking benzodiazepines regularly at one or more phases . These men showed a marked increased incidence of dementia ( OR=3.50 , 95 % CI 1.57 to 7.79 , p=0.002 ) , which persisted despite adjustment for psychological distress and other covariates . Men exposed in earlier phases showed a greater association than more recent exposure , counter to what one would expect if this was due to reverse causation , though we failed to demonstrate a dose – response effect with drug duration . Conclusion The taking of benzodiazepines is associated with an increased risk of dementia BACKGROUND Ongoing regimens of haloperidol , thioridazine , and lorazepam are commonly administered to manage behavior problems in nursing home residents . Nevertheless , there is controversy over whether periodic drug withdrawal should be attempted when those medications are prescribed . This study addressed that issue by examining the effects of discontinuing treatment with haloperidol , thioridazine , and lorazepam among residents of a large suburban nursing home . METHODS In a double-blind , crossover study , half of 58 nursing home residents ( 43 women and 15 men with a mean age of 86 years ) continued to take the psychotropic medication they had been prescribed , whereas the other half were tapered to placebo . After 6 weeks of taking placebo or original drug , patients were tapered to the reverse schedule and remained on it for 6 weeks . Assessment s included informant ratings by the nursing staff who completed the Brief Psychiatric Rating Scale and the Cohen-Mansfield Agitation Inventory . RESULTS Analyses comparing residents taking placebo to those taking medication after completion of the first phase showed no impact of drug therapy discontinuation on their behavior . Similarly , using the crossover design to compare residents ' behaviors while taking placebo vs. taking drugs , withdrawal of medication had no impact on Cohen-Mansfield Agitation Inventory or Brief Psychiatric Rating Scale scores . CONCLUSIONS Results of this work suggest that longterm use of haloperidol , thioridazine , and lorazepam in nursing homes to manage agitation should be closely monitored for their efficacy . Furthermore , routine attempts at drug withdrawal should be considered for most residents taking psychotropic medication A double-blind study was performed to evaluate carbamazepine for the prophylaxis of benzodiazepine withdrawal syndrome in elderly patients --a controversial subject despite the extensive use of such drugs in old age . Thirty-six out patients aged > or = 60 yrs suffering from general anxiety disorders and benzodiazepine abuse underwent gradual discontinuation of benzodiazepine therapy in two groups , one treated with carbamazepine and one with placebo . The carbamazepine-treated group demonstrated a lower incidence of withdrawal symptoms rated according to the Physician Withdrawal Check List ( p < 0.01 ) , better results with the Hopkins Symptom Check List ( Covi cluster , p < 0.01 ) and a more markedly reduced score with the Hamilton Rating Scale for Anxiety ( p < 0.05 ) . Only 3 out of 18 patients in said group complained of side effects attributable to carbamazepine , which disappeared at lower dosages Thirty-one patients dependent on benzodiazepines were r and omly assigned to either slow withdrawal ( SW ) or abrupt withdrawal under propranolol cover ( PW ) . Of 16 patients in the SW group , 11 successfully withdrew from their drugs , while only 4 out of 15 in the PW group did so . Patients in the SW group had only mild withdrawal symptoms , while those in the PW group suffered more severe symptoms , which lasted around four weeks . In all , 81 % of the whole group suffered withdrawal symptoms of some kind . Patients in both groups were significantly less anxious at the end of the study than at baseline . Younger subjects and those who were more severely anxious at the start of the trial had more difficulty in withdrawing than older and less anxious patients Pretreatment with imipramine , buspirone , or placebo was compared in 40 patients meeting the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition criteria for panic disorder and in patients who were discontinuing long-term benzodiazepine use . The average duration of benzodiazepine use was 75 ± 64 months , and the average benzodiazepine intake expressed as diazepam equivalents was 25.7 ± 19 mg/d . We hypothesized that pretreatment with either imipramine or buspirone , in contrast to pretreatment with placebo , would lead to a significant decrease of symptoms of anxiety and depression before tapering benzodiazepines , thus making the taper process easier to complete . All 3 treatments ( imipramine , buspirone , and placebo ) caused a reduction in anxiety and depression symptoms as measured by changes in the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale . Neither discontinuation severity nor taper-free status 12 weeks posttaper differed between the 3 treatment groups OBJECTIVE Patients with generalized anxiety disorder ( N=107 ) who had been long-term benzodiazepine users ( average duration of use=8.5 years ) were enrolled in a benzodiazepine discontinuation program that assessed the effectiveness of concomitant imipramine ( 180 mg/day ) and buspirone ( 38 mg/day ) compared to placebo in facilitating benzodiazepine discontinuation . METHOD After a benzodiazepine stabilization period taking either diazepam , lorazepam , or alprazolam , patients were treated for 4 weeks with imipramine , buspirone , or placebo under double-blind conditions while benzodiazepine intake was kept stable ( treatment phase ) . Patients then entered a 4 - 6 week benzodiazepine taper and a 5-week posttaper phase with imipramine , buspirone , and placebo treatment being continued until 3 weeks into the posttaper phase , at which time all patients were switched to placebo for 2 weeks . Benzodiazepine plasma levels were assayed weekly . Benzodiazepine-free status was assessed 3 and 12 months posttaper . RESULTS Study subjects were long-term benzodiazepine users with an average of three unsuccessful prior taper attempts . The success rate of the taper in this study was significantly higher for patients who received imipramine ( 82.6 % ) , and nonsignificantly higher for patients who received buspirone ( 67.9 % ) , than for patients who received placebo ( 37.5 % ) . The imipramine effect remained highly significant even after the analysis adjusted for three other independent predictors of taper success : benzodiazepine dose , level of anxious symptoms at baseline , and duration of benzodiazepine therapy . CONCLUSIONS Management of benzodiazepine discontinuation can be facilitated significantly by co-prescribing imipramine before and during the benzodiazepine taper . Daily benzodiazepine dose , severity of baseline symptoms of anxiety and depression , and duration of benzodiazepine use were additional significant predictors of successful taper outcome The aim of the trial was to assess alpidem efficacy in preventing and treating the benzodiazepine ( BZ ) withdrawal syndrome ( WS ) . A multicentre , double-blind , r and omized versus placebo , parallel group study of six-week duration was carried out in out patients suffering from generalized anxiety or adjustment disorder with an anxious mood and taking non-hypnotic BZ as continuous course of therapy of at least one-year duration . At the entry , the patients abruptly discontinued BZs and were treated with 50 mg/bid/tid of alpidem or placebo . Withdrawal syndrome diagnosis was ( regarding treatment allocation ) formulated by an independent psychiatrist , according to DSM-III-R and an appropriate scale , the SESSB . One hundred seventy-three patients were r and omized and 148 completed the study . Withdrawal syndrome occurred in 27 patients of the alpidem group ( 31.0 % ) and in 38 patients of the placebo group ( 44.2 % ) . A severe WS was diagnosed in 11.1 % of the patients in the alpidem group and in 31.6 % of the placebo group . If not having been withdrawn from the market , alpidem could have been useful for the prevention of BZ withdrawal syndrome To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines , out patients ( N = 106 ) with a lifetime diagnosis of generalized anxiety disorder ( current diagnosis could be subthreshold ) who had been treated with a benzodiazepine for 8–52 weeks were stabilized for 2–4 weeks on alprazolam in the range of 1–4 mg/day . Patients were then r and omized to 12 weeks of double-blind treatment with either pregabalin 300–600 mg/day or placebo while undergoing a gradual benzodiazepine taper at a rate of 25 % per week , followed by a 6-week benzodiazepine-free phase during which they continued double-blind study treatment . Outcome measures included ability to remain benzodiazepine-free ( primary ) as well as changes in Hamilton Anxiety Rating Scale (HAM)-A and Physician Withdrawal Checklist ( PWC ) . At endpoint , a non-significant higher proportion of patients remained benzodiazepine-free receiving pregabalin compared with placebo ( 51.4 % vs 37.0 % ) . Treatment with pregabalin was associated with significantly greater endpoint reduction in the HAM-A total score versus placebo ( −2.5 vs + 1.3 ; p < 0.001 ) , and lower endpoint mean PWC scores ( 6.5 vs 10.3 ; p = 0.012 ) . Thirty patients ( 53 % ) in the pregabalin group and 19 patients ( 37 % ) in the placebo group completed the study , reducing the power to detect a significant difference on the primary outcome . The results on the anxiety and withdrawal severity measures suggest that switching to pregabalin may be a safe and effective method for discontinuing long-term benzodiazepine therapy The objective of this study was to compare the efficacy of homeopathic drugs Homéogène 46 and Sédatif PC with a placebo as substitute for benzodiazepines in patients treated for at least 3 months with low doses ( less than 10 mg/d of diazepam equivalents ) . A double-blind r and omized trial was carried out in general practice . The treatment lasted one month . Several rating scales were used . The main outcome was success/failure defined according to the doctor 's clinical judgement and interruption of treatment . A total of 61 patients were r and omized , and 19 interrupted their treatment . Comparability between the groups was good . No statistically significant difference between homeopathic drugs and placebo was observed for the main outcome or for the secondary outcomes . The lack of statistical power due to accrual difficulties limits the conclusions of this trial which did not confirm the efficacy of homeopathic drugs in this indication SUMMARY Background and objectives : Discontinuation of benzodiazepines can be associated with the emergence of a withdrawal syndrome which compromises successful termination of treatment . The objective of the present study was to evaluate whether a six week administration of captodiamine during benzodiazepine discontinuation could prevent emergence of a benzodiazepine withdrawal syndrome and thus facilitate discontinuation of these drugs . Subjects and methods : A controlled , r and omised , double-blind trial of captodiamine versus placebo was conducted in 81 subjects presenting mild to moderate anxiety and treated for at least 6 months with a stable dose of benzodiazepine . Each subject was gradually weaned from benzodiazepines over a 14 day period using a tapering dose schedule and received captodiamine ( 150 mg/d ) or placebo for 45 days from the beginning of the weaning period . Outcome measures : The primary outcome criterion was the extent of withdrawal symptoms assessed using the Tyrer Benzodiazepine Withdrawal Symptom Question naire . Secondary outcome criteria were ; self-evaluation of tension , anxiety , drowsiness and slowing of physical and mental performance using visual analogue scales ; quality of sleep using the Spiegel question naire ; anxiety using the Hamilton Anxiety Rating Scale ; and cognitive function using a driving stimulation test . Results : Analysis of the primary study criterion revealed a statistically significant difference ( p < 0.0001 ) in the emergence of withdrawal symptoms between the two groups in favour of captodiamine at two , six and eight weeks following initiation of therapy . These results were supported by significant beneficial effects of captodiamine on the majority of secondary outcome measures . The switch to captodiamine was associated with an improvement in vigilance , which may be an advantage for the overall safety of the anxiolytic treatment , for example with regard to road safety . Discontinuation of captodiamine was not associated with the emergence of rebound anxiety . Conclusion : Captodiamine represents an interesting strategy for achieving benzodiazepine substitution with a low risk of dependence or impairment of cognitive function . Further clinical studies addressing the anxiolytic activity and safety of captodiamine in such subjects are merited Benzodiazepines are frequently long-term prescribed for the treatment of patients with severe mental illness . This prescribing practice is problematic because of well-described side effects including risk of dependence . We examined the efficacy of prolonged-release melatonin on objective and subjective sleep quality during benzodiazepine discontinuation and whether sleep variables were associated with benzodiazepine withdrawal . Eligible patients included adults with a diagnosis of schizophrenia , schizoaffective disorder , or bipolar disorder and long-term use of benzodiazepines in combination with antipsychotics . All participants gradually tapered the use of benzodiazepines after r and omization to add-on treatment with melatonin versus placebo . Here we report a sub sample of 23 patients undergoing sleep recordings ( one-night polysomnography ) and 55 patients participating in subjective sleep quality ratings . Melatonin had no effect on objective sleep efficiency , but significantly improved self-reported sleep quality . Reduced benzodiazepine dosage at the 24-week follow-up was associated with a significantly decreased proportion of stage 2 sleep . These results indicate that prolonged-release melatonin has some efficacy for self-reported sleep quality after gradual benzodiazepine dose reduction , and that benzodiazepine discontinuation is not associated with rebound insomnia in medicated patients with severe mental illness . However , these findings were limited by a small sample size and a low retention rate PATIENTS AND METHODS 154 out patients with generalized anxiety ( DSM III-R criteria ) , followed by general practitioners , gave an informed written consent to participate in this multicenter , r and omized , placebo controlled study previously approved by a legal ethic committee ( CCPPRB ) . The patients had to be long term consumers ( at least 3 months ) of 2 mg daily of lorazepam and were withdrawn using transiently an antihistaminic anxiolytic ( hydroxyzine or placebo TAD ) according to 6 different procedures defining 6 parallel groups : hydroxyzine 50 mg , abrupt or progressive withdrawal ; hydroxyzine 25 mg , abrupt or progressive withdrawal ; placebo , abrupt or progressive withdrawal . Following this 4 week-period of withdrawal , the patients were without any treatment for a post- study follow up 2 month-period . Clinical evaluations for anxiety ( HARS , Zung ) , sleep ( Spiegel ) , BZD withdrawal syndrome ( Tyrer ) , adverse reactions and clinical global impression ( CGI ) were performed at D0 , D7 , D14 , D28 , D35 and D88 . Investigators opinion and patients attitude towards BZD were collected at D88 . STATISTICAL ANALYSIS Analysis of variance for quantitative variables and chi square test for qualitative or ordinal variables . RESULTS Whatever abrupt or progressive , with or without hydroxyzine support , using half or full dosage , lorazepam withdrawal proved to be feasible even after a long term BZD treatment ( mean = 64 months + /- 60 ) . GPs opinion ( 72 % satisfied : D35 ; 78 % satisfied : D88 ) is satisfying but patients attitude ( at D88 : 54 % patients desired to be regiven a tranquilizer , 31 % patients occasionally had a BZD and 22 % formally dem and ed a prescription of BZD ) is more question able . Despite a high initial level of anxiety under lorazepam ( HARS = 21 + /- 10 at D0 ) , after a one-month period of withdrawal ( under placebo or hydroxyzine ) followed by a 2 month-period without any treatment , 75 % patients were totally free of any drug and their level of anxiety was significantly decreased ( D88 : HARS = 12 + /- 9 ) . Progressive withdrawal appeared preferable if compared to abrupt since the number of drop outs between D28 and D88 was less important and the procedure judged more favourably by the patients . Levels of anxiety significantly decreased in both the groups ( progressive and abrupt ) but sleep parameters and number of withdrawal symptoms between D7 and D28 were improved only in abrupt withdrawal group ( p < 0.0001 ) . Considering hydroxyzine , 2 patients dropped out between D0 and D28 in the group hydroxyzine 25 mg , 6 patients in the group 50 mg and 5 patients in the group placebo . Levels of anxiety ( HARS et Zung ) were significantly improved in hydroxyzine 50 mg group ( p < 0.007 ) and in hydroxyzine 25 mg group ( p < 0.012 ) but not in placebo group . Withdrawal symptoms ( Tyrer ) between D0 and D28 were improved only in hydroxyzine 50 mg group and the number of side effects was significantly improved in both the hydroxyzine ( 25 et 50 mg ) groups but not in placebo group . However , no significant difference was found between the 3 groups . Daytime sleepiness is more frequent in hydroxyzine 50 mg group . DISCUSSION These results proved a significant improvement of anxiety , a decrease of side effects in both the groups treated with hydroxyzine and a reduction of withdrawal symptomatology in hydroxyzine 50 mg group . When a patient is engaged to be withdrawn from of a lorazepam long term treatment , it can therefore be proposed as a support a transient prescription of hydroxyzine 25 mg TAD to markedly anxious patients and of hydroxyzine 50 mg TAD to patients presenting a withdrawal symptomatology OBJECTIVE This study was design ed to examine the possibility that patients with panic disorder are especially vulnerable to alprazolam withdrawal , as well as to evaluate the efficacy of carbamazepine as adjunctive treatment during alprazolam discontinuation . METHOD After a 2-month open trial of alprazolam , 36 patients with panic disorder and 35 with generalized anxiety disorder entered a controlled discontinuation phase . Carbamazepine or placebo was added in a r and omized , double-blind fashion , followed after 1 week by single-blind dose reduction of alprazolam , approximately 25 % every third day . RESULTS Fifty-two percent of the patients were able to discontinue alprazolam , but only 37 % completed the study , maintaining alprazolam-free status for 4 weeks . Survival analysis revealed that among the patients receiving placebo as adjunctive therapy , panic disorder patients had a significantly greater dropout rate than patients with generalized anxiety disorder . While carbamazepine exerted no beneficial effect for patients with generalized anxiety disorder , it appeared to improve outcome in the panic disorder group . CONCLUSIONS Results of this study indicate that panic disorder patients are more vulnerable to alprazolam withdrawal than patients with generalized anxiety disorder , and this may reflect a general diathesis of panic disorder patients to encounter more difficulty during drug withdrawal . Carbamazepine may selectively assist with alprazolam withdrawal in panic disorder patients . However , these data do not support its widespread use during benzodiazepine discontinuation , especially given its potential toxicity . In light of a proposed greater vulnerability of panic disorder patients to withdrawal , future studies need to account for differential effects related to specific diagnosis Sleep quality and anxiety levels were examined using question naires and polysomnographic recordings in 22 chronic insomnia patients who regularly used benzodiazepines to treat their sleeping problems . After abruptly discontinuing their benzodiazepine medication , patients were r and omly allocated to receive either a placebo or zolpidem 10 mg for 1 week , after which they entered an open extension phase , receiving zolpidem 10 mg for 3 weeks . Subjectively , sleep quality was considered mediocre during the use of a benzodiazepine hypnotic . One week after the discontinuation , an increase in sleep latency was observed in the placebo group , whereas zolpidem induced a significant decrease in sleep latency . Deterioration of other sleep variables ( probably rebound ) was not suppressed by zolpidem . An explanation for this could be the selective pharmacological profile of zolpidem . Polysomnographic differences between placebo and benzodiazepine and between placebo and zolpidem were not reflected by the subjective data on sleep and anxiety . Changes of sleep structure caused by hypnotics seem not always to be felt as such by patients . After 3 – 4 weeks of zolpidem treatment , the percentage of non-rapid eye movement-4 sleep increased significantly , corresponding with a significant subjective improvement of sleep quality . This indicates that zolpidem may restore physiological sleep A double-blind placebo-controlled trial of 23 chronic benzodiazepine users showed that overall , buspirone did not appear to be helpful in alleviating benzodiazepine withdrawal symptoms . Buspirone ( 5 mg t.d.s . ) or placebo was administered for four weeks before , during and after diazepam withdrawal . Patients taking buspirone had a markedly higher dropout rate ( seven out of 11 ) than those taking placebo ( one out of 12 ) . Mean daily diazepam dosage at entry was significantly higher in the buspirone group , but overall initial diazepam dosage was not related to outcome . Higher subjectively rated anxiety at the start of withdrawal was significantly related to higher dropout rate , irrespective of treatment , and was greater ( although not significantly so ) in the buspirone group Forty patients with a history of difficulty discontinuing long-term , daily benzodiazepine therapy were r and omly assigned , under double-blind conditions , to treatment with carbamazepine ( 200 to 800 mg/d ) or placebo . A gradual taper ( 25 % per week reduction ) off benzodiazepine therapy was then attempted . Five weeks after taper , significantly more patients who had received carbamazepine than placebo remained benzodiazepine free , this despite the fact that no statistically significant differences in withdrawal severity could be demonstrated . Patients receiving carbamazepine reported a larger reduction in withdrawal severity than patients receiving placebo , but only at a trend level , and only on the daily patient-rated withdrawal checklist . Eleven patients ( 28 % ) required antidepressant therapy for depression or panic when assessed at 12-weeks follow-up . The results of this pilot investigation suggest that carbamazepine might have promise as an adjunctive drug therapy for the benzodiazepine withdrawal syndrome , particularly in patients receiving benzodiazepines in daily dosages of 20 mg/d or greater of diazepam equivalents Chronic benzodiazepine ( BDZ ) users often have difficulty with BDZ withdrawal . To examine clinical effects of selective serotonin reuptake inhibitor ( SSRI ) on tapering BDZ use in non-depressive patients , 97 out patients with a history of BDZ use for at least 3 months were recruited at an internal medicine clinic of a university hospital . After the 4th edition of the Diagnostic and Statistical Manual ( DSM-IV ) clinical interviews for screening major depression , 66 out patients ( 68 % ) without the DSM-IV major depression were r and omly assigned to one of three groups : SSRI-assisted BDZ-reduction group ( 10 - 20 mg of paroxetine , n = 22 ) , simple BDZ-reduction group ( no paroxetine , n = 23 ) , and reference group ( no BDZ-reduction , n = 21 ) . A st and ardized 8-week program involving gradual BDZ discontinuation was performed in the two BDZ-reduction groups . The Hamilton Rating Scales for Depression ( HAM-D ) and Anxiety ( HAM-A ) and the BDZ Withdrawal Symptom Question naire were assessed during the intervention period . Those with major depression were excluded from the BDZ-reduction intervention and treated with a different protocol of medication . In total , 10 ( 45.5 % ) in the SSRI-assisted BDZ-reduction group ( n = 22 ) succeeded in becoming BDZ-free after completing the program , whereas only four ( 17.4 % ) in the simple BDZ-reduction group ( n = 23 ) succeeded . The assistance of the SSRI significantly predicted the success of becoming BDZ-free ( P = 0.023 ) , controlling for the effects of age , gender , period of BDZ use , and baseline HAM-D and HAM-A scores . The score changes on the three question naires were comparable ( all P > 0.05 ) among the three groups during the intervention period . The use of SSRI may have beneficial effects on BDZ withdrawal without the worsening of mood states in cases without major depression AIM We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam , zopiclone or zolpidem ( here ' BZD ' ) use . METHODS A double-blind , placebo-controlled , r and omized trial was conducted in a primary health care outpatient clinic . Ninety-two men or women ( ≥55 years ) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg ( CRM ) ( n = 46 ) or placebo ( n = 46 ) during the 1 month withdrawal from BZDs . Psychosocial support was provided . Follow-up continued for up to 6 months . Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations , while reduction in BZD use and abstinence continuing for 6 months were noted . RESULTS There were two drop-outs on CRM and one on placebo . After a 1 month withdrawal , 31 participants ( 67 % ; 95 % CI 54 , 81 ) on CRM and 39 ( 85 % ; 74 , 95 ) on placebo had withdrawn completely ( intention-to-treat analysis between groups , P = 0.051 ; per protocol P = 0.043 ) . Reduction in BZD use was similar or even more rare in the CRM than in the placebo group ( P = 0.052 per protocol ) . After 6 months , 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD ( NS between groups ) . BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up ( P = 0.025 ) . Withdrawal symptoms did not differ between the groups . CONCLUSIONS Gradual dose reduction of BZDs combined with CRM or placebo , and psychosocial support produced high short term and moderate long term BZD abstinence . CRM showed no withdrawal benefit compared with placebo |
12,405 | 25,007,974 | Subgroup analysis of patients with extraperitoneal cancer showed equivalent involvement of the circumferential margin in the two treatment groups .
The sensitivity and subgroup analyses revealed no other significant differences between laparoscopic and open surgery in the rate of R0 resections , distal margin clearance , mesorectal fascia integrity , or local recurrence at 5 years .
Conclusions Based on the evidence from RCTs and non- RCTs , the short-term benefit and oncological adequacy of laparoscopic rectal resection appear to be equivalent to open surgery , with some evidence potentially pointing to comparable long-term outcomes and oncological adequacy in selected patients with primary resectable rectal cancer | Background This review of cancer outcomes is based on key literature search es of the medical data bases and meta- analysis of short-term benefits of laparoscopy in rectal cancer treatment . | Background The role of laparoscopic resection ( LR ) in the management of extraperitoneal rectal cancer still is unclear . This study aim ed to compare perioperative and long-term results of laparoscopic and open resection ( OR ) for low and midrectal cancer . Methods A prospect i ve nonr and omized trial comparing patients su bmi tted to OR or LR for low and midrectal cancer at a single institution was conducted . Results The study included 191 consecutive patients : 98 patients who underwent LR and 93 who underwent OR . The mean follow-up period was 46.3 months for LR and 49.7 months for OR . The conversion rate for LR was 18.4 % . With the use of LR , the mean time for complete patient mobilization was shorter ( 1.7 vs 3.3 days ; p < 0.001 ) and patients were earlier in passing flatus ( 2.6 vs 3.9 days ; p < 0.001 ) and stools ( 3.8 vs 4.7 days ; p < 0.01 ) , and in resuming oral intake ( 3.4 vs 4.8 days ; p < 0.001 ) . The mean hospital stay was shorter for LR , but the difference did not reach significance ( 11.4 vs 13 days ) . Morbidity and mortality rates were similar : LR ( 24.4 % and 1 % ) and OR ( 23.6 % and 2.2 % ) . Laparoscopic patients presented a higher rate of anastomotic fistulas ( 13.5 % vs 5.1 % ) and reoperations ( 6.1 % vs 3.2 % ) but the difference was statistically nonsignificant . Laparoscopic resection presented a significantly lower local recurrence rate ( 3.2 % vs 12.6 % ; p < 0.05 ) . The cumulative survival and disease-free rates at 5 years were , respectively , 80 % and 65.4 % after LR and 68.9 % and 58.9 % after OR ( nonsignificant difference ) . Stage-by-stage comparison showed prolonged cumulative survival for stages III and IV cancer in LR ( 82.5 % vs 40.5 % ; p = 0.006 and 15.8 % vs 0 % ; p = 0.013 , respectively ) and a reduced rate of cancer-related death for stage III in LR ( 11.4 % vs 51.9 % ; p = 0.001 ) . Conclusions As compared with conventional open surgery , LR for low and midrectal cancer is characterized by a faster recovery and similar overall morbidity ( but a higher rate of anastomotic leakages ) , and does not present any adverse oncologic effect BACKGROUND Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe . The aim in the COlorectal cancer Laparoscopic or Open Resection ( COLOR II ) trial was to compare laparoscopic and open surgery in patients with rectal cancer . METHODS A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries . Patients ( aged ≥18 years ) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were r and omly assigned to either laparoscopic or open surgery in a 2:1 ratio , stratified by centre , location of tumour , and preoperative radiotherapy . The study was not masked . Secondary ( short-term ) outcomes -including operative findings , complications , mortality , and results at pathological examination-are reported here . Analysis was by modified intention to treat , excluding those patients with post-r and omisation exclusion criteria and for whom data were not available . This study is registered with Clinical Trials.gov , number NCT00297791 . FINDINGS The study was undertaken between Jan 20 , 2004 , and May 4 , 2010 . 1103 patients were r and omly assigned to the laparoscopic ( n=739 ) and open surgery groups ( n=364 ) , and 1044 were eligible for analyses ( 699 and 345 , respectively ) . Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group ( median 200 mL [ IQR 100 - 400 ] vs 400 mL [ 200 - 700 ] , p<0·0001 ) ; however , laparoscopic procedures took longer ( 240 min [ 184 - 300 ] vs 188 min [ 150 - 240 ] ; p<0·0001 ) . In the laparoscopic surgery group , bowel function returned sooner ( 2·0 days [ 1·0 - 3·0 ] vs 3·0 days [ 2·0 - 4·0 ] ; p<0·0001 ) and hospital stay was shorter ( 8·0 days [ 6·0 - 13·0 ] vs 9·0 days [ 7·0 - 14·0 ] ; p=0·036 ) . Macroscopically , completeness of the resection was not different between groups ( 589 [ 88 % ] of 666 vs 303 [ 92 % ] of 331 ; p=0·250 ) . Positive circumferential resection margin ( < 2 mm ) was noted in 56 ( 10 % ) of 588 patients in the laparoscopic surgery group and 30 ( 10 % ) of 300 in the open surgery group ( p=0·850 ) . Median tumour distance to distal resection margin did not differ significantly between the groups ( 3·0 cm [ IQR 2·0 - 4·8 ] vs 3·0 cm [ 1·8 - 5·0 ] , respectively ; p=0·676 ) . In the laparoscopic and open surgery groups , morbidity ( 278 [ 40 % ] of 697 vs 128 [ 37 % ] of 345 , respectively ; p=0·424 ) and mortality ( eight [ 1 % ] of 699 vs six [ 2 % ] of 345 , respectively ; p=0·409 ) within 28 days after surgery were similar . INTERPRETATION In selected patients with rectal cancer treated by skilled surgeons , laparoscopic surgery result ed in similar safety , resection margins , and completeness of resection to that of open surgery , and recovery was improved after laparoscopic surgery . Results for the primary endpoint-locoregional recurrence-are expected by the end of 2013 . FUNDING Ethicon Endo-Surgery Europe , Swedish Cancer Foundation , West Gothia Region , Sahlgrenska University Hospital Purpose Laparoscopic surgery of colon cancer has been accepted to be oncologically adequate compared with open resection . However , the situation in rectal cancer remains unclear , because anatomy and complex surgical procedures might specifically influence the long-term outcome . This study was design ed to analyze perioperative and long-term outcome of patients with rectal cancer after laparoscopic vs. open access surgery . Methods A total of 389 patients ( 1998–2005 ) were prospect ively analyzed ; 114 patients had laparoscopic beginning , and 25 patients had conversion and were separately analyzed . Eighty-nine patients remained in the laparoscopic group and 275 had open access surgery . Results Both groups were comparable regarding age , gender , tumor localization , stage , and complications . Differences were found in harvested lymph nodes ( laparoscopic 13.5/open access 16.9 ; P = 0.001 ) and hospitalization ( 15.1/18.7 days ; P = 0.037 ) . Local recurrence rate and metachronous metastasis were comparable . In patients with deep anterior resection with total mesenteric excision , favorable long-term survival in the laparoscopic group was found ( P = 0.035 , log-rank ) . Conclusions Minimally invasive surgery is equivalent in the treatment of rectal cancer and shows advantages of shorter hospitalization and faster recovery . Especially in patients with low rectal cancer , minimally invasive surgery with exact preparation of the total mesenteric excision seems to be favorable compared with open access surgery BACKGROUND Minimally invasive , laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer . Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence ( based on frequent reports of tumor recurrences within surgical wounds ) prompted a controlled trial evaluation . METHODS We conducted a noninferiority trial at 48 institutions and r and omly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons . The median follow-up was 4.4 years . The primary end point was the time to tumor recurrence . RESULTS At three years , the rates of recurrence were similar in the two groups--16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group ( two-sided P=0.32 ; hazard ratio for recurrence , 0.86 ; 95 percent confidence interval , 0.63 to 1.17 ) . Recurrence rates in surgical wounds were less than 1 percent in both groups ( P=0.50 ) . The overall survival rate at three years was also very similar in the two groups ( 86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group ; P=0.51 ; hazard ratio for death in the laparoscopic-surgery group , 0.91 ; 95 percent confidence interval , 0.68 to 1.21 ) , with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer . Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group , as reflected by a shorter median hospital stay ( five days vs. six days , P<0.001 ) and briefer use of parenteral narcotics ( three days vs. four days , P<0.001 ) and oral analgesics ( one day vs. two days , P=0.02 ) . The rates of intraoperative complications , 30-day postoperative mortality , complications at discharge and 60 days , hospital readmission , and reoperation were very similar between groups . CONCLUSIONS In this multi-institutional study , the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy , suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent in the open group ( P = 0.18 ) . The mean length of hospital stay was 10 ( 4.9 ) days in the laparoscopic group and 13.6 ( 10 ) days in the open group ( P = 0.004 ) . Local recurrence rate and five-year survival were similar in both groups ; however , the limited number of patients does not allow firm conclusions . Quality of life was better in the laparoscopic group only in the first year after surgery ( P < 0.0001 ) . The additional charge in the laparoscopic group was $ 1,748 per patient r and omized ( $ 1,194 the result of surgical instruments and $ 554 the result of longer operative time ) . The saving in the laparoscopic group was $ 1,396 per patient r and omized ( $ 647 the result of shorter length of hospital stay and $ 749 the result of the lower cost of postoperative complications ) . The net balance result ed in $ 351 extra cost per patient r and omly allocated to the laparoscopic group . Conclusions Short-term postoperative morbidity was similar in the two groups . Laparoscopic resection reduced length of hospital stay , improved first-year quality of life , and slightly increased hospital costs BACKGROUND The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable . The multicentre COLOR ( COlon cancer Laparoscopic or Open Resection ) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon . METHODS 627 patients were r and omly assigned to laparoscopic surgery and 621 patients to open surgery . The primary endpoint was cancer-free survival 3 years after surgery . Secondary outcomes were short-term morbidity and mortality , number of positive resection margins , local recurrence , port-site or wound-site recurrence , metastasis , overall survival , and blood loss during surgery . Analysis was by intention to treat . Here , clinical characteristics , operative findings , and postoperative outcome are reported . FINDINGS Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection ( median 100 mL [ range 0 - 2700 ] vs 175 mL [ 0 - 2000 ] , p<0.0001 ) , although laparoscopic surgery lasted 30 min longer than did open surgery ( p<0.0001 ) . Conversion to open surgery was needed for 91 ( 17 % ) patients undergoing the laparoscopic procedure . Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups . Laparoscopic colectomy was associated with earlier recovery of bowel function ( p<0.0001 ) , need for fewer analgesics , and with a shorter hospital stay ( p<0.0001 ) compared with open colectomy . Morbidity and mortality 28 days after colectomy did not differ between groups . INTERPRETATION Laparoscopic surgery can be used for safe and radical resection of cancer in the right , left , and sigmoid colon AIM To evaluate the feasibility of laparoscopic resection of rectal carcinoma and to compare the short-term outcome of laparoscopic procedure with conventional open surgery for rectal cancer . METHODS Thirty-eight patients with rectal cancer were included in a prospect i ve non-r and omized study . The patients were assigned to laparoscopic ( n=18 ) or open ( n=18 ) colorectal resection . Case selection , surgical technique , and clinical and pathological results were review ed . RESULTS The operative time was longer in laparoscopic resection group ( LAP ) than in open resection group ( 189+/-18 min vs 146+/-22 min , P<0.05 ) . Intraoperative blood loss and postoperative complications were less in LAP resection group than in open resection group . An earlier return of bowel motility was observed after laparoscopic surgery . The overall postoperative morbidity was 5.6 % in the LAP resection group and 27.8 % in open resection group ( P<0.05 ) . No anastomotic leakage was found in both groups . The pathologic examination showed that the length of the resected specimen , the mean number of harvested lymph nodes in laparoscopic resection group were comparable to those in open resection group . CONCLUSION Laparoscopic total mesorectal excision ( TME ) for rectal cancer is a feasible but technically dem and ing procedure . The present study demonstrates the safety of the procedure , while oncologic results are comparable to the open surgery , with a favorable short-term outcome Purpose This study was design ed to compare the outcomes of laparoscopic anterior resection with open operation for mid and upper rectal cancer . Methods A total of 265 patients who underwent elective laparoscopic or open anterior resection for cancer of the mid and upper rectum from June 2000 to December 2004 were included . Data about the patients ’ demographics , operative details , postoperative outcome , and disease status were collected prospect ively . Comparison of the outcome between laparoscopic and open resection was performed . Results The median age of the 265 patients was 69 ( range , 27–91 ) years , and laparoscopic anterior resection was performed in 98 patients ( 37 percent ) . There was no difference in the age , gender , comorbidities , and level of tumor between the two groups . The operating time was longer in the laparoscopic group ( 200 vs. 127 minutes ; P < 0.01 ) , but the blood loss was less ( 200 vs. 250 ml ; P = 0.027 ) . The overall operative mortality was 1.8 percent , and the complication rate was 27.9 percent . Significantly more patients with early diseases ( Stage I and Stage II ) were operated with laparoscopic approach . There was no difference in the mortality or morbidity between the two groups . Anastomotic leakage occurred in five patients with open resection and one with laparoscopic resection ( P = 0.418 ) . Patients with laparoscopic resection had an earlier return of bowel function and earlier resumption of diet as well as a shorter median hospital stay ( 7 vs. 8 days ; P < 0.001 ) . With the median follow-up of the surviving patients for 21.2 months , the three-year local recurrence rates for those with open and laparoscopic resection were 4.9 and 3.3 percent , respectively ( P = 0.513 ) . In patients with Stage I and Stage II disease , the three-year cancer-specific survivals for open and laparoscopic resection were 89.8 and 88.6 percent , respectively ( P = 0.882 ) , whereas those of patients with Stage III disease were 65.6 and 55.5 percent , respectively ( P = 0.911 ) . Conclusions Laparoscopic anterior resection for mid and proximal rectal cancer is a safe option with short-term advantages compared with open operation . The oncologic outcomes of patients who underwent laparoscopic anterior resection were not compromised , with similar local recurrence rate and the cancer-specific survival rate as patients who underwent open resection PURPOSE : The aim of the study is to assess the safety and oncologic feasibility of laparoscopic-assisted resection for rectal cancer vs open rectal resection as a phase II pilot study for a planned r and omized control trial . METHODS : A case-matched controlled prospect i ve analysis of 54 patients who underwent laparoscopic-assisted resection for stage I to III ( no T4 ) rectal cancer within 12 cm of the anal verge from 2002 to 2005 was performed . Patients were matched with contemporary patients who underwent open rectal cancer surgery ( n = 108 ) in a 1 to 2 fashion . The perioperative clinical outcomes , postoperative pathology , and oncologic outcomes were compared between the groups . RESULTS : The demographic data did not differ significantly between the groups . The laparoscopic group manifested early return of bowel function ( P = .003 ) . The complication rate was 22.2 % in the laparoscopic group and 32.4 % in the open group ( P = .178 ) . Local recurrence was similar ( 2.0 % laparoscopic , 4.2 % open , P = .417 ) . The 5-year overall and disease-free survival rate also were similar ( overall survival , 90.8 % laparoscopic , 88.5 % open , P = .261 ; disease-free survival , 80.8 % laparoscopic , 75.8 % open . P = .390 ) . CONCLUSION : The laparoscopic-assisted resection for rectal cancer was acceptable in terms of oncologic outcomes and perioperative clinical outcomes . The present data are the basis for a large-scale r and omized trial for comparison of laparoscopic and open rectal cancer surgeries ( American College of Surgeons Oncology Group Z6051 ) Background and aims Because definitive long-term results are not yet available , the oncological safety of laparoscopic surgery for treatment of rectal cancer remains unproven . The aim of this prospect i ve non-r and omised study was to assess the feasibility and short-term outcome of laparoscopic total mesorectal excision ( LTME ) after 25–30 Gy preoperative radiotherapy and to compare the results with a matched-control group of open TME ( OTME ) . Material s and methods A series of 41 patients with primary rectal cancer underwent LTME for rectal cancer and were matched with a historical control group of 41 patients who underwent OTME . Both groups received preoperative short-term radiotherapy . Results There was no mortality in the LTME group and 2 % mortality in the OTME group . The overall postoperative morbidity was 37 % in the LTME group and 51 % in the OTME group , including an anastomotic leakage of 9 and 14 % in the LTME and OTME groups respectively . A positive circumferential margin was found in 7 % of patients in the LTME group and in 12 % of the patients in the OTME group . Conclusion This study shows that LTME is technically feasible and can be performed safely . We show at least a similar surgical completeness using a laparoscopic technique compared with open surgery Objective To compare laparoscopic versus open surgery for rectal cancer and analyse the results of the multidisciplinary audited project on total mesorectal excision conducted in Spain . Background The safety and therapeutic efficiency of laparoscopic surgery for rectal cancer are controversial due to the technical difficulties it involves . A deviation from the oncological principles of mesorectal excision would mean a potential increase in local recurrence and shorter survival . Methods This prospect i ve non-r and omised multicentre study includes 4,970 patients with rectal cancer . The study compares perioperative , postoperative , anatomicopathological and survival variables . Results Five hundred and sixty five patients were excluded . Of the remaining 4,405 , 3,018 ( 68.51 % ) had open surgery ( OS ) and 1,387 ( 31.49 % ) laparoscopic surgery ( LS ) . The rate of anterior resections was higher in the LS group . The rate of intraoperative tumour perforation , number of red blood cell concentrates transfused and length of hospital stay were greater in the OS group , whereas surgical time was longer in the LS group . The incidence of complications was 45.6 % in the OS group and 38.3 % in the LS group . Involvement of the circumferential and distal margin , as well as unsatisfactory and partially satisfactory quality of the mesorectum , were greater in the OS group . There were no differences for local recurrence and survival rates . Conclusions According to these results , laparoscopic surgery is the best option for the surgical treatment of rectal cancer , with similar rates of local recurrence and survival , although there are oncological indicators in this study to suggest that these results can be improved with laparoscopic surgery OBJECTIVE To examine the role of total mesorectal excision in the management of rectal cancer . DESIGN A prospect i ve consecutive case series . SETTING A district hospital and referral center in Basingstoke , Engl and . PATIENTS Five hundred nineteen surgical patients with adenocarcinoma of the rectum treated for cure or palliation . INTERVENTIONS Anterior resections ( n = 465 ) with low stapled anastomoses ( 407 total mesorectal excisions ) , abdominoperineal resections ( n = 37 ) , Hartmann resections ( n = 10 ) , local excisions ( n = 4 ) , and laparotomy only ( n = 3 ) . Preoperative radiotherapy was used in 49 patients ( 7 with abdominoperineal resections , 38 with anterior resections , 3 with Hartmann resections , and 1 with laparotomy ) . MAIN OUTCOME MEASURES Local recurrence and cancer-specific survival . RESULTS Cancer-specific survival of all surgically treated patients was 68 % at 5 years and 66 % at 10 years . The local recurrence rate was 6 % ( 95 % confidence interval , 2%-10 % ) at 5 years and 8 % ( 95 % confidence interval , 2%-14 % ) at 10 years . In 405 " curative " resections , the local recurrence rate was 3 % ( 95 % confidence interval , 0%-5 % ) at 5 years and 4 % ( 95 % confidence interval , 0%-8 % ) at 10 years . Disease-free survival in this group was 80 % at 5 years and 78 % at 10 years . An analysis of histopathological risk factors for recurrence indicates only the Dukes stage , extramural vascular invasion , and tumor differentiation as variables in these results . CONCLUSIONS Rectal cancer can be cured by surgical therapy alone in 2 of 3 patients undergoing surgical excision in all stages and in 4 of 5 patients having curative resections . In future clinical trials of adjuvant chemotherapy and radiotherapy , strategies should incorporate total mesorectal excision as the surgical procedure of choice BACKGROUND : Laparoscopic resection for rectal cancer has remained controversial because of the lack of level 1 evidence regarding oncologic safety and long-term survival . OBJECTIVES : The aim of this study was to assess the impact of laparoscopic versus open resection for rectal cancer on clinical and oncologic outcome in the multimodal setting . DESIGN : This is a review of prospect ively gathered data from a single-institution rectal cancer data base . SETTING S : This study was conducted in the Central Hospital of Central Finl and . PATIENTS : From January 1999 to December 2006 , 191 selected patients were included . INTERVENTIONS : One hundred patients underwent laparoscopic resection , and 91 patients , also suitable for laparoscopic surgery , underwent open major rectal resection in the multimodal setting . MAIN OUTCOME MEASURES : The main measures of outcome were early recovery and short- and long-term morbidity ; local recurrence and survival were secondary outcomes . LIMITATIONS : This is not a r and omized study . RESULTS : The study groups were balanced for baseline characteristics . Conversion rate to open surgery was 22 % . Laparoscopic surgery result ed in significantly less bleeding ( 175 mL vs 500 mL , p < 0.001 ) , 1 day earlier recovery of normal diet ( 3 days vs 4 days , p = 0.001 ) , and shorter postoperative hospital stay ( 7 days vs 9 days , p < 0.001 ) . Postoperative 30-day mortality ( 1 % vs 3 % ) , morbidity ( 31 % vs 43 % ) , readmission ( 11 % vs 15 % ) , and reoperation ( 6 % vs 9 % ) rates were similar in the 2 groups , but significantly fewer patients in the laparoscopic group had long-term complications ( 19 % vs 36 % , p = 0.033 ) . The 5-year disease-free survival ( 78 % vs 80 % , p = 0.74 ) and local recurrence ( 5 % vs 6 % , p = 0.66 ) rates were similar in the laparoscopic and open group for those 175 patients treated for cure . CONCLUSION : Laparoscopic surgery result ed in faster postoperative recovery and fewer long-term complications than open surgery without apparently compromising the long-term oncologic outcome . Our results indicate that laparoscopic rectal resection is an acceptable alternative to open surgery in selected patients with rectal cancer BACKGROUND Laparoscopic total mesorectal excision ( TME ) is being used in rectal cancer more frequently . The aim of this study was to analyze the differences in short-term outcomes between open and laparoscopic TME . METHODS In this nonr and omized consecutive study , the short-term outcomes of 100 patients undergoing TME for proven rectal cancer were analyzed . RESULTS Two groups of 50 patients underwent an open or laparoscopic TME for rectal cancer . Both groups were comparable . Laparoscopic surgery took longer to perform ( 250 vs. 197.5 min , p < 0.01 ) , but was accompanied by less blood loss ( 350 vs. 800 ml , p < 0.01 ) . Enteric function recovered sooner after laparoscopy . The numbers of major and minor complications were comparable between both groups , although fewer patients had major complications in the laparoscopic group ( 6 vs. 15 patients , p = 0.03 ) . Hospital stay was shorter for patients who underwent a laparoscopic abdominoperineal resection ( 10 vs. 12 days , p = 0.04 ) . Median follow-up was 17 months for the laparoscopic group and 22 months for the open group . Survival analyses between the groups showed no statistical difference in disease-free and overall survival . CONCLUSION This study shows that laparoscopic TME for rectal cancer is a safe and feasible technique with some short-term benefits over open TME Abstract PURPOSE : This study was conducted to investigate the feasibility of laparoscopic resection of rectal cancer and to compare early outcome data with the results of the conventional technique . METHODS : From January 1996 to March 2002 , 435 patients with primary rectal cancer were operated on at our institution . Low-risk , small rectal tumors treatable by local excision , rectal cancer recurrences , and emergency cases were excluded from the analysis . Three hundred thirty-four patients were operated on by the conventional open approach . One hundred one selected patients underwent surgery by the laparoscopic technique . RESULTS : Because of the selection process , significantly more patients with early tumor stages were operated on by laparoscopy . There were no differences in mean operation time , morbidity , mortality , or the anastomotic leakage rate ; however , the need for intraoperative transfusion , mean stay in the intensive care unit , and length of hospital stay were reduced significantly . CONCLUSIONS : In terms of the intraoperative and early postoperative course , the laparoscopic resection of rectal cancer in a selected cohort of patients compares favorably with the open technique . Because follow- up time is limited to date , only very preliminary information can be given on tumor-related outcome data . However , these preliminary data appear to suggest that rectal cancer resection can be performed by laparoscopy in accordance with established principles of cancer therapy and that port-site metastases are not a relevant clinical problem . Prospect i ve , r and omized trials are required to determine whether the laparoscopic approach will play a significant role in the treatment of rectal cancer in the future BACKGROUND : Evidence demonstrates short-term benefits of laparoscopic surgery for colon cancer . The situation for rectal cancer is less clear . OBJECTIVES : This review assessed the use and short-term outcomes of elective open and laparoscopic colon and rectal cancer resections within an area health service . DESIGN : This was a multicenter , retrospective review of a prospect i ve data base . SETTING S : All elective colon and rectal cancer resections in the western zone of Sydney South West Area Health Service from 2001 until 2008 were included . PATIENTS : Included were 1721 patients who underwent either a laparoscopic colon ( n = 434 ) or rectal ( n = 157 ) resection or an open colon ( n = 742 ) or rectal ( n = 388 ) resection . MAIN OUTCOME MEASURES : Outcome measures included operating time , blood loss , adequacy of resection , conversion rate , intensive care unit admission , length of stay , and 26 acute postoperative complications . RESULTS : Patients were matched for age , sex , ASA , BMI , and tumor stage . Laparoscopic surgery increased in frequency . Fewer patients experienced a complication in both the laparoscopic colon ( 28.8 vs 54.4 % ; p < 0.0001 ) and rectal ( 41.4 vs 60.3 % ; p < 0.0001 ) group irrespective of age . Laparoscopic operating time for colon and rectal cancer was 24.1 minutes ( p < 0.0001 ) and 25.8 minutes ( p < 0.0001 ) longer , with a low conversion-to-open rate ( 6.5 % and 8.3 % ; p = 0.44 ) . Laparoscopic surgery result ed in fewer transfusions ( 0.4 vs 0.7units ; p = 0.0028 ) and length of stay ( 7 vs 10 days ; p = 0.0011 ) for colon cancers , and reduced intraoperative hemoglobin drop ( 20.5 vs 24.8 ; p = 0.029 ) and intensive care unit admissions ( 26.8 vs 36.3 % ; p = 0.032 ) for rectal cancers . LIMITATIONS : This was a nonr and omized study with rectal cancers more often resected with the open technique ( 71.2 vs 28.8 % ; p < 0.001 ) . CONCLUSIONS : Within an area health service , elective laparoscopic resection for colon and rectal cancer had improved short-term outcomes in comparison with open surgery Background This single-center , prospect i ve , r and omized trial was design ed to compare the short-term clinical outcome between laparoscopic-assisted versus open total mesorectal excision ( TME ) with anal sphincter preservation ( ASP ) in patients with mid and low rectal cancer . Long-term morbidity and survival data also were recorded and compared between the two groups . Methods Between August 2001 and August 2007 , 80 patients with mid and low rectal cancer were r and omized to receive either laparoscopic-assisted ( 40 patients ) or open ( 40 patients ) TME with ASP . The median follow-up time for all patients was 75.7 ( range 16.9–115.7 ) months for the laparoscopic-assisted group and 76.1 ( range 4.7–126.6 ) months for the open group . The primary endpoint of the study was short-term clinical outcome . Secondary endpoints included long-term morbidity rate and survival . Data were analyzed by intention-to-treat principle . Results The demographic data of the two groups were comparable . Postoperative recovery was better after laparoscopic surgery , with less analgesic requirement ( P < 0.001 ) , earlier mobilization ( P = 0.001 ) , lower short-term morbidity rate ( P = 0.043 ) , and a trend towards shorter hospital stay ( P = 0.071 ) . The cumulative long-term morbidity rate also was lower in the laparoscopic-assisted group ( P = 0.019 ) . The oncologic clearance in terms of macroscopic quality of the TME specimen , circumferential resection margin involvement , and number of lymph nodes removed was similar between both groups . After curative resection , the probabilities of survival at 5 years of the laparoscopic-assisted and open groups were 85.9 and 91.3 % , respectively ( P = 0.912 ) . The respective probabilities of being disease-free were 83.3 and 74.5 % ( P = 0.114 ) . Conclusions Laparoscopic-assisted TME with ASP improves postoperative recovery , reduces short-term and long-term morbidity rates , and seemingly does not jeopardize survival compared with open surgery for mid and low rectal cancer ( http:// Clinical Trials.gov Identifier : NCT00485316 ) BACKGROUND The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated . The aim of the r and omised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy ( COREAN ) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy . METHODS Between April 4 , 2006 , and Aug 26 , 2009 , patients with cT3N0 - 2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals . Patients were r and omised 1:1 to receive either open surgery ( n=170 ) or laparoscopic surgery ( n=170 ) , stratified according to sex and preoperative chemotherapy regimen . Short-term outcomes assessed were involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , recovery of bowel function , perioperative morbidity , postoperative pain , and quality of life . Analyses were based on the intention-to-treat population . Patients continue to be followed up for the primary outcome ( 3-year disease-free survival ) . This study is registered with Clinical Trials.gov , number NCT00470951 . FINDINGS Two patients ( 1.2 % ) in the laparoscopic group were converted to open surgery , but were included in the laparoscopic group for analyses . Estimated blood loss was less in the laparoscopic group than in the open group ( median 217.5 mL [ 150.0 - 400.0 ] in the open group vs 200.0 mL [ 100.0 - 300.0 ] in the laparoscopic group , p=0.006 ) , although surgery time was longer in the laparoscopic group ( mean 244.9 min [ SD 75.4 ] vs 197.0 min [ 62.9 ] , p<0.0001 ) . Involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , and perioperative morbidity did not differ between the two groups . The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group ( time to pass first flatus , median 38.5 h [ 23.0 - 53.0 ] vs 60.0 h [ 43.0 - 73.0 ] , p<0.0001 ; time to resume a normal diet , 85.0 h [ 66.0 - 95.0 ] vs 93.0 h [ 86.0 - 121.0 ] , p<0.0001 ; time to first defecation , 96.5 h [ 70.0 - 125.0 ] vs 123 h [ 94.0 - 156.0 ] , p<0.0001 ) . The total amount of morphine used was less in the laparoscopic group than in the open group ( median 107.2 mg [ 80.0 - 150.0 ] vs 156.9 mg [ 117.0 - 185.2 ] , p<0.0001 ) . 3 months after proctectomy or ileostomy takedown , the laparoscopic group showed better physical functioning score than the open group ( 0.501 [ n=122 ] vs -4.970 [ n=128 ] , p=0.0073 ) , less fatigue ( -5.659 [ n=122 ] vs 0.098 [ n=129 ] , p=0.0206 ) , and fewer micturition ( -2.583 [ n=122 ] vs 4.725 [ n=129 ] , p=0.0002 ) , gastrointestinal ( -0.400 [ n=122 ] vs 4.331 [ n=129 ] , p=0.0102 ) , and defecation problems ( 0.535 [ n=103 ] vs 5.327 [ n=99 ] , p=0.0184 ) in repeated measures analysis of covariance , adjusted for baseline values . INTERPRETATION Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery ; the quality of oncological resection was equivalent BACKGROUND The long-term survival and safety of laparoscopic surgery in patients with rectal cancer remain unclear . The aim of this trial was to assess the efficacy and safety of laparoscopic surgery for treatment of rectal cancer . METHODS We undertook a r and omized , controlled trial in 343 patients with rectal cancer between May 2004 and April 2008 . One hundred sixty-nine patients were r and omly assigned to laparoscopic surgery and 174 patients to open surgery . The main endpoint was 3-year survival . Data were analyzed according to the intention-to-treat principle . RESULTS Laparoscopic surgery was associated with earlier recovery of bowel movement compared with open surgery . The average time to first discharge , bowel movement , resumption of fluid intake , and activity out of bed in laparoscopic surgery were shorter by 0.63 , 0.32 , 0.33 , and 0.63 day , respectively ( P < .001 ) . The incidences of postoperative morbidities such as infectious complications , anastomotic leakage , anastomotic stenosis , and deep vein thrombosis have no differences . No differences were found in the comparison of long-term survival . INTERPRETATION Laparoscopic surgery for rectal cancer is as safe and effective as open surgery in terms of oncology outcomes . Long-term survival for patients with rectal cancer undergoing laparoscopic surgery were similar to those undergoing conventional open surgery , thus supporting the continued use of laparoscopic surgery in Chinese patients with rectal cancer Background Laparoscopic resection of colonic cancer has been shown to improve postoperative recovery without jeopardizing tumor clearance and survival , but information on low rectal cancer is scarce . The aim of this r and omized trial was to compare postoperative recovery between laparoscopic-assisted versus open abdominoperineal resection ( APR ) in patients with low rectal cancer . Recurrence and survival data were also recorded and compared between the two groups . Methods Between September 1994 and February 2005 , 99 patients with low rectal cancer were r and omized to receive either laparoscopic-assisted ( 51 patients ) or conventional open ( 48 patients ) APR . The median follow-up time of living patients was about 90 months for both groups . The primary and secondary endpoints of the study were postoperative recovery and survival , respectively . Data were analyzed by intention-to-treat principle . Results The demographic data of the two groups were comparable . Postoperative recovery was better after laparoscopic surgery , with earlier return of bowel function ( P < .001 ) and mobilization ( P = .005 ) , and less analgesic requirement ( P = .007 ) . This was at the expense of longer operative time and higher direct cost . There were no differences in morbidity and operative mortality rates between the two groups . After curative resection , the probabilities of survival at 5 years of the laparoscopic-assisted and open groups were 75.2 % and 76.5 % respectively ( P = .20 ) . The respective probabilities of being disease-free were 78.1 % and 73.6 % ( P = .55 ) . Conclusions Laparoscopic-assisted APR improves postoperative recovery and seemingly does not jeopardize survival when compared with open surgery for low rectal cancer . A larger sample size is needed to fully assess oncological outcomes BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use |
12,406 | 28,315,933 | More recent studies appeared to fare more favourably in terms of pain outcomes and operating time .
The coblation technique appears to be comparable with other commonly employed techniques for tonsillectomy ; however , there is still no strong evidence to suggest that it possesses any definitive benefits . | Coblation is one of the more recent techniques for tonsillectomy ; however , it remains unclear whether it exhibits any benefit or increased risk when compared to other techniques .
This review provides an up date d assessment of coblation tonsillectomy and how it compares to other tonsillectomy techniques . | OBJECTIVES To assess the morbidity and efficacy of bipolar radiofrequency thermal ablation tonsillectomy and compare it with traditional cold dissection tonsillectomy with diathermy hemostasis . DESIGN Prospect i ve , r and omized , single-blinded , controlled clinical study . SETTING Helsinki University Central Hospital , Department of Otorhinolaryngology-Head & Neck Surgery , Helsinki , Finl and . PATIENTS Forty healthy volunteer patients aged 18 to 65 years admitted for elective tonsillectomy with recurrent or chronic tonsillitis , obstructive tonsillar hypertrophy , or history of quinsy . Two patients were excluded from the study and 1 patient cancelled the operation . INTERVENTIONS Nineteen patients underwent a traditional cold dissection tonsillectomy with diathermy hemostasis , and 18 patients underwent a bipolar radiofrequency thermal ablation tonsillectomy . There was no intergroup difference in age , sex , weight , and indications for tonsillectomy . The subjects were not informed of the type of procedure until the telephone interview 3 weeks after the operation . MAIN OUTCOME MEASURES Operating time and intraoperative blood loss ; need for anesthetics during the operation ; different recovery indicators in the recovery room ( ie , duration and medications administered ) , surgical ward ( ie , medications administered , use of corticosteroids , general condition , and status of the uvula on the first postoperative day ) , and in the 2 weeks following surgery ( ie , visual analog scale scores on 6 symptoms , medications needed , the day patients returned to work , use of antibiotics , and retreatment acceptance ) ; and complications and certain laboratory parameters . RESULTS There was a statistically significant but clinical ly insignificant difference in operating time and intraoperative blood loss in favor of the traditional tonsillectomy group . The other outcome measures showed no statistically significant differences . CONCLUSION Bipolar radiofrequency thermal ablation and traditional tonsillectomy were associated with similar postoperative morbidity OBJECTIVE Tonsillectomy has been described using a number of techniques . Recently Coblation Technology has been used to remove tonsils with anecdotal evidence of a reduction in post-operative morbidity . In this study we aim to see if there is any difference in post-operative pain , tonsillar fossae healing and return to a normal diet performing tonsillectomy , using tissue coblation compared with st and ard bipolar dissection . METHODS A double blind r and omised control trial to compare the technique of tissue coblation with st and ard bipolar dissection to remove tonsils in 38 children on the waiting list for tonsillectomy , with a history of chronic tonsillitis or obstructive tonsils . RESULTS A significant reduction in post-operative pain was found in the children whose tonsils were removed by tissue coblation ( P<0.0001 ) . More rapid healing of the tonsillar fossae was found in the coblation group . Children who had their tonsils removed by coblation were found to return to their normal diet far sooner than those who underwent bipolar dissection . There were no episodes of primary or secondary haemorrhage in either group . CONCLUSIONS This new technique using tissue coblation for tonsil removal offers significant advantages in the post-operative period , with rapid return to a normal diet and a drastic reduction in analgesic requirements following the surgery Objectives Coblation is operated in low temperature , so it is proposed that tonsillectomy with coblation involves less postoperative pain and allows accelerated healing of the tonsillar fossae compared with other methods involving heat driven processes . However , the results of the previous studies showed that the effect of coblation tonsillectomy has been equivocal in terms of postoperative pain and hemorrhage . Though , most of the previous studies which evaluated coblation tonsillectomy were performed in children . Recently , electrocautery tonsillectomy has been used most widely because of the reduced intraoperative blood loss and shorter operative time compared to other techniques . This prospect i ve study compared intraoperative records and postoperative clinical outcomes in adolescents and adults following coblation and electrocautery tonsillectomies . Methods Eighty patients over 16 years of age with histories of recurrent tonsillitis were enrolled . The patients were r and omly allocated into coblation ( n=40 ) and electrocautery tonsillectomy groups ( n=40 ) . All operations were performed by one surgeon who was skilled in both surgical techniques . Intraoperative parameters and postoperative outcomes were checked . Results Postoperative pain and otalgia were not significantly different between the two groups ; however , there was a tendency towards reduced pain and otalgia in the coblation group . More cotton balls for swabbing the operative field were used introoperatively in the electrocautery group ( P=0.00 ) . There was no significant difference in postoperative hemorrhage , wound healing , commencement of a regular diet , and foreign body sensation between the groups . Conclusion Only cotton use , which represented the amount of blood loss , was less in the coblation tonsillectomy group . Coblation tonsillectomy warrants further study with respect to the decreased postoperative pain and otalgia Coblation tonsillectomy has shown promising results with respect to postoperative pain when compared with other techniques . Our study was design ed to compare this technique with bipolar scissor tonsillectomy . Forty adult patients with a history of chronic or recurrent tonsillitis referred for st and ard tonsillectomy were recruited and r and omized into two groups . Twenty were operated with Coblator and 20 with bipolar scissors . Exclusion criteria were a history of quinsy , bleeding disorder , or any major health problems . All participants completed the study . Postoperative pain , return to normal diet , and estimated need for sick leave were utilized as parameters . Data on operative time , difficulty of tissue removal , and hemostasis were also analyzed . Operative time was longer ( P < 0.001 ) and tissue removal as well as hemostasis control were more difficult ( P = 0.005 , P = 0.013 ) with Coblator than with bipolar scissors . Participants in Coblator group assessed higher pain scores 1 and 3 h postoperatively ( P = 0.044 , P = 0.036 ) . From the time of extubation , patients had access to an opioid ( fentanyl ) via a self-controlled analgesia device . The number of doses of analgesics needed during the hospital stay was significantly higher in the Coblator group ( P = 0.020 ) . During the 14-day follow-up , no significant differences were found in pain scores , return to solid food or subjective working ability between the groups . Considering the overall outcome of the patients the results did not favor coblation technique over bipolar scissors The aim of this prospect i ve r and omized single blind study was to determine the depth of thermal damage to tonsillar tissue due to coblation , and to compare it with thermal damage to tonsillar tissue following conventional tonsillectomy ; to correlate the depth of thermal damage to tonsillar tissue with the parameters of postoperative morbidity , to compare intraoperative blood loss , postoperative pain severity , time to resuming normal physical activity , and incidence of postoperative bleeding between two groups of tonsillectomized children aged up to 16 years . 72 children aged 3 - 16 years scheduled for tonsillectomy r and omly assigned into two groups su bmi tted either to conventional tonsillectomy with bipolar diathermy coagulation or to coblation tonsillectomy , with a 14-day follow up . Statistically significant differences were observed in the depth of thermal damage to tonsillar tissue ( p < 0.001 ) , intraoperative blood loss ( p < 0.004 ) , in postoperative pain severity ( p < 0.05 ) and in time to resuming normal physical activity between the two groups ( p < 0.001 ) . There was no case of reactionary or secondary bleeding in either group . In this paper for the first time we have correlated postoperative morbidity and thermal tissue damage : less thermal damage is associated with less postoperative morbidity OBJECTIVE To compare plasma-mediated ablation ( PMA ) with monopolar electrosurgery ( MES ) for pediatric tonsillectomy . DESIGN Prospect i ve , r and omized , blinded study . SETTING Academic children 's hospital . PARTICIPANTS Thirty-four children , aged 4 to 7 years . INTERVENTIONS Tonsillectomy by means of PMA ( n = 17 ) or MES ( n = 17 ) . OUTCOME MEASURES We measured surgical efficacy , estimated blood loss , and surgical time during tonsillectomy and morphine use , immediate postoperative pain , and recovery scores after tonsillectomy . Parents recorded recovery of normal diet and activity and their own return to work for 10 days after surgery . Histopathologic evaluation of excised tonsils was performed . We review ed medical records and attempted follow-up telephone contact . RESULTS With no significant difference in blood loss compared with MES , PMA was effective for tonsillectomy . Performance of PMA took longer ( 24 vs 16 minutes ; P = .002 ) . Results of histopathologic evaluation showed less thermal injury with PMA than with MES ( P = .03 ) . Morphine consumption , pain , and recovery scores were equivalent between groups . We found no significant difference in recovery of normal diet and activity or parental return to work . Patients undergoing PMA had a greater number of perioperative complications than those undergoing MES , including 2 patients in the PMA group ( compared with none in the MES group ) who required unplanned admission for postoperative airway obstruction . CONCLUSIONS Plasma-mediated ablation for pediatric tonsillectomy result ed in less histopathologic thermal injury than MES , but did not show a statistically faster recovery to normal activity and diet or parental return to work . In addition , PMA took longer to perform , and had more complications . Therefore , PMA should not replace MES for pediatric tonsillectomy . The reduced thermal injury with PMA supports investigation into other means of using plasma ablation to treat tonsillar hypertrophy OBJECTIVE To conduct an adequately powered , prospect i ve , r and omised , controlled trial comparing adult dissection tonsillectomy using either ultrasonic scalpel , bipolar electrocautery , bipolar radiofrequency or ' cold steel ' dissection . METHODS Three hundred patients were r and omised into four tonsillectomy technique groups . The operative time , intra-operative bleeding , post-operative pain , tonsillar fossa healing , return to full diet , return to work and post-operative complications were recorded . RESULTS The bipolar radiofrequency group had a shorter mean operative time . The mean intra-operative blood loss during bipolar radiofrequency tonsillectomy was significantly less compared with cold dissection and ultrasonic scalpel tonsillectomy . Pain scores were significantly higher after bipolar electrocautery tonsillectomy . Patients undergoing bipolar electrocautery tonsillectomy required significantly more days to return to full diet and work . The bipolar electrocautery group showed significantly reduced tonsillar fossa healing during the first and second post-operative weeks . CONCLUSION In this adult series , bipolar radiofrequency tonsillectomy was superior to ultrasonic , bipolar electrocautery and cold dissection tonsillectomies . This method combines the advantages of ' hot ' and ' cold ' tonsillectomy Objectives : The aim of this study was to compare postoperative symptoms following coblation tonsillectomy with those experienced following a traditional cold dissection Objective Comparison of coblation and monopolar electrocautery tonsillectomy in terms of postoperative pain and recovery . Study Design Prospect i ve double-blind r and omized controlled trial . Methods Patients with recurrent tonsillitis requiring tonsillectomy were r and omized to 2 groups : coblation or monopolar electrocautery tonsillectomy . Postoperative pain , complications , and days taken to return to work and normal diet were compared and analyzed with the aid of a pain diary , given to the patient . Results 67 patients were recruited . Patients undergoing coblation tonsillectomy were able to return to normal diet in a shorter space of time following surgery . Patients undergoing coblation tonsillectomy were more likely to recommend the surgery than patients undergoing electrocautery tonsillectomy . No significant differences in the daily visual analog score for pain were seen for both groups of patients . Conclusions Our results showed that coblation tonsillectomy has a faster recovery period and may offer advantages when compared to monopolar electrocautery tonsillectomy OBJECTIVES To compare the advantages and disadvantages of potassium titanyl phosphate laser with those of bipolar radiofrequency techniques , in paediatric tonsillectomy . STUDY DESIGN Prospect i ve , r and omised , clinical study . PATIENTS AND METHODS From July 2004 to April 2006 , 80 patients aged between 10 and 15 years , with tonsillectomy planned for chronic tonsillitis , were included in the study . Children were prospect ively r and omised into two equal groups : potassium titanyl phosphate laser tonsillectomy and bipolar radiofrequency tonsillectomy . Operative time and intra-operative blood loss were recorded . Patients were scheduled for follow up during the first , second and fourth post-operative weeks . They were asked to record their pain and discomfort on a st and ardised visual analogue scale , from zero ( no pain ) to 10 ( severe pain ) . Post-operative complications were also recorded and managed . RESULTS The potassium titanyl phosphate laser group showed a slightly longer operative time ( mean 12 minutes ) than the bipolar radiofrequency group ( mean 10 minutes ) . Intra-operative blood loss was significantly less in the potassium titanyl phosphate laser group ( mean 21 cm3 ) than in the bipolar radiofrequency group ( mean 30 cm3 ) . In the first week , post-operative pain scores were less in the potassium titanyl phosphate laser group than in the bipolar radiofrequency group ( means 7.5 and 8.5 , respectively ) . However , in the second week pain scores increased more in the potassium titanyl phosphate laser group than in the bipolar radiofrequency group ( means 8.5 and 6 , respectively ) . In the fourth week , both groups showed equal and nearly normal pain scores . No case of reactionary post-tonsillectomy haemorrhage was recorded in either group . Only one case of secondary post-tonsillectomy haemorrhage was recorded , in the potassium titanyl phosphate laser group ( 2.5 per cent ) , managed conservatively . CONCLUSION Both the potassium titanyl phosphate and the bipolar radiofrequency techniques were safe and easy to use for tonsillectomy , with reduced operative time , blood loss and complication rates and better post-operative general patient condition . Potassium titanyl phosphate laser result ed in reduced operative bleeding and immediate post-operative pain , compared with the bipolar radiofrequency technique . However , potassium titanyl phosphate laser required slightly more operative time and caused more late post-operative pain than the bipolar radiofrequency technique . The low rate of recorded complications showed that both techniques cause little damage to the tonsillar bed during dissection , thus minimising complications INTRODUCTION Adenotonsillectomy is one of the most common surgical procedures throughout the world for children in otolaryngology . One of the current indications for adenotonsillectomy is adenotonsillar hypertrophy causing Obstructive Sleep Apnoea ( OSA ) . The choice of surgical tools and technique affects the outcome and morbidity due to adenotonsillectomy . AIM OF THE STUDY To assess the efficacy and safety of coblation adenotonsillectomy as compared to dissection method . To evaluate the morbidity and to study complications associated with each procedure . MATERIAL S AND METHODS This prospect i ve and comparative study of dissection and coblation method of adenotonsillectomy was conducted in our institute , Madras ENT Research Foundation , Chennai over a period of 6 months . 50 cases of children with OSA age group between 5 and 12 years were r and omly selected for each group and studied . Duration of surgical procedure , blood loss , post operative pain , post operative reactionary and secondary bleeding was noted and compared . OBSERVATION AND RESULTS Operative time was more in dissection method compared to coblation technique . Blunt dissection tonsillectomy was associated with greater blood loss than coblation tonsillectomy . Post operative pain was more in dissection method and it was less in coblation technique . Post operative bleeding in both the techniques were found to be minimal . CONCLUSION We conclude that the use of coblation for adenotonsillectomy may have several advantages over st and ard methods for the treatment of children with Obstructive Sleep Apnoea . It is highly efficacious , practical and safe with less morbidity and less complications OBJECTIVES : To compare postoperative tonsillectomy pain between 3 commonly used surgical devices : the Harmonic Ultrasonic Scalpel ( Ethicon Endo-Surgery , Cincinnati , OH ) , the Coblator ( ArthroCare Corp , Sunnyvale , CA ) , and electrocautery . STUDY DESIGN AND SETTING : A prospect i ve , r and omized trial . One hundred thirty-four patients were r and omly assigned to receive a tonsillectomy with 1 of 3 surgical devices . All patients were asked to fill out a postoperative diary . RESULTS : Statistically significant differences in pain scores were revealed between the Coblator and electrocautery ( P = 0.02 ) and between the Coblator and the Ultrasonic Scalpel ( P = 0.003 ) , with the Coblator having lower pain scores . Electrocautery and the Ultrasonic Scalpel did not differ significantly from each other . The Coblation method showed a strong trend toward quicker return to normal diet . CONCLUSION : Patients undergoing tonsillectomy with the Coblator device reported less pain over a 10-day period than patients undergoing tonsillectomy with electrocautery or the Ultrasonic Scalpel . Pain after tonsillectomy remains a major issue for our patients . The choice of surgical instrument appears to be one way to reduce this pain . EBM rating : OBJECTIVE To compare and analyse the efficiency of the low-temperature plasma radiofrequency and the traditional method in tonsillectomy . METHOD Sixty-four patients with chronic tonsillitis were r and omly divided into group A ( 39 cases ) and group B ( 25 cases ) . Patients in the group A were treated with traditional method tonsillectomy while patients in the group B were treated with low-temperature plasma radio frequency tonsillectomy . Analysed differences in operation time , blood loss , and postoperative pain as well as the incidence of postoperative between two groups . RESULT There were significant differences in operative time , blood loss , and postoperative pain ( P < 0.05 ) between two groups , but there was no obvious difference in the incidence of postoperative bleeding ( P > 0.05 ) . CONCLUSION Low-temperature plasma radiofrequency tonsillectomy is a safer method and has many superiorities including shorter operative time , less blood loss , quicker recovery of postoperative pain compared with traditional tonsillectomy OBJECTIVE This is a prospect i ve study evaluating certain intraoperative and postoperative parameters , comparing the relatively new technique of thermal welding tonsillectomy with cold knife tonsillectomy , and radiofrequency excision in pediatric population . METHODS Ninety children aged from 5 through 13 years were enrolled a r and omized prospect i ve trial comparing cold knife tonsillectomy , radiofrequency excision , and thermal welding tonsillectomy . Indications included recurrent acute tonsillitis and /or obstructive sleep apnea syndrome . All techniques were compared by means of length of surgery time , blood loss , postoperative bleeding and postoperative pain . RESULTS Sixty-eight patients underwent tonsillectomy for obstructive sleep apnea , whereas 22 children underwent tonsillectomy due to recurrent acute tonsillitis . Median values of all variables tested , length of surgery time , blood loss , postoperative bleeding and postoperative pain , were found to differ significantly among the three surgical techniques ( P<0.001 ) . Particularly , a statistically significant higher median duration ( P<0.001 ) and intraoperative blood loss ( P<0.001 ) , as well as , a statistically significant lower median pain score in each day tested ( P<0.001 ) of the cold knife group , compared to each one of the other two groups , were found . Tissue welding and radiofrequency groups did not differ significantly in any aspect tested . CONCLUSIONS Both thermal welding and radiofrequency excision techniques have shown comparable results regarding intraoperative blood loss , postoperative hemorrhage , and pain . Compared with cold knife tonsillectomy , welding and radiofrequency excision techniques were associated with less intraoperative blood loss and duration , though cold knife tonsillectomy seems to prevail over the two techniques in terms of the postoperative pain |
12,407 | 22,696,348 | Available evidence suggests that behavioral interventions for tobacco cessation conducted by oral health professionals incorporating an oral examination component in the dental office or community setting may increase tobacco abstinence rates among both cigarette smokers and smokeless tobacco users .
Differences between the studies limit the ability to make conclusive recommendations regarding the intervention components that should be incorporated into clinical practice , however , behavioral counselling ( typically brief ) in conjunction with an oral examination was a consistent intervention component that was also provided in some control groups | BACKGROUND Tobacco use has significant adverse effects on oral health .
Oral health professionals in the dental office or community setting have a unique opportunity to increase tobacco abstinence rates among tobacco users .
OBJECTIVES This review assesses the effectiveness of interventions for tobacco cessation delivered by oral health professionals and offered to cigarette smokers and smokeless tobacco users in the dental office or community setting . | Smoking exerts detrimental effects on dental treatment and oral health . Our goal was to evaluate effectiveness in terms of the abstinence rate in smoking-cessation intervention delivered by dental professionals . Individuals who were willing to quit smoking were r and omly assigned to either an intervention or a non-intervention group . Intensive intervention was provided , consisting of 5 counseling sessions , including an additional nicotine replacement regimen . Reported abstinence was verified by the salivary cotinine level . Thirty-three persons in the intervention and 23 in the non-intervention group started the trial . On an intent-to-treat basis , 3- , 6- and 12-month continuous abstinence rates in the intervention group were 51.5 % , 39.4 % , and 36.4 % , respectively , while the rates in the non-intervention group were consistent at 13.0 % . Adjusted odds ratios ( 95 % confidence interval ) by logistic stepwise regression analyses were 7.1 ( 1.8 , 28.5 ) , 8.9 ( 1.7 , 47.2 ) , and 6.4 ( 1.3 , 30.7 ) , respectively . Intensive smoking-cessation intervention in the dental setting was therefore effective Background Tobacco use continues to be a global public health problem . Helping patients to quit is part of the preventive role of all health professionals . There is now increasing interest in the role that the dental team can play in helping their patients to quit smoking . The aim of this study was to determine the feasibility of undertaking a r and omised controlled smoking cessation intervention , utilising dental hygienists to deliver tobacco cessation advice to a cohort of periodontal patients . Methods One hundred and eighteen patients who attended consultant clinics in an outpatient dental hospital department ( Periodontology ) were recruited into a trial . Data were available for 116 participants , 59 intervention and 57 control , and were analysed on an intention-to-treat basis . The intervention group received smoking cessation advice based on the 5As ( ask , advise , assess , assist , arrange follow-up ) and were offered nicotine replacement therapy ( NRT ) , whereas the control group received ' usual care ' . Outcome measures included self-reported smoking cessation , verified by salivary cotinine measurement and CO measurements . Self-reported measures in those trial participants who did not quit included number and length of quit attempts and reduction in smoking . Results At 3 months , 9/59 ( 15 % ) of the intervention group had quit compared to 5/57 ( 9 % ) of the controls . At 6 months , 6/59 ( 10 % ) of the intervention group quit compared to 3/57 ( 5 % ) of the controls . At one year , there were 4/59 ( 7 % ) intervention quitters , compared to 2/59 ( 4 % ) control quitters . In participants who described themselves as smokers , at 3 and 6 months , a statistically higher percentage of intervention participants reported that they had had a quit attempt of at least one week in the preceding 3 months ( 37 % and 47 % , for the intervention group respectively , compared with 18 % and 16 % for the control group ) . Conclusion This study has shown the potential that trained dental hygienists could have in delivering smoking cessation advice . While success may be modest , public health gain would indicate that the dental team should participate in this activity . However , to add to the knowledge-base , a multi-centred r and omised controlled trial , utilising biochemical verification would be required to be undertaken Background The dental visit is a unique opportunity for tobacco control . Despite evidence of effectiveness in dental setting s , brief provider-delivered cessation advice is underutilized . Objective To evaluate an Internet-delivered intervention design ed to increase implementation of brief provider advice for tobacco cessation in dental practice setting s. Methods Dental practice s ( N = 190 ) were r and omized to the intervention website or wait-list control . Pre-intervention and after 8 months of follow-up , each practice distributed exit cards ( brief patient surveys assessing provider performance , completed immediately after the dental visit ) to 100 patients . Based on these exit cards , we assessed : whether patients were asked about tobacco use ( ASK ) and , among tobacco users , whether they were advised to quit tobacco ( ADVISE ) . All intervention practice s with follow-up exit card data were analyzed as r and omized regardless of whether they participated in the Internet-delivered intervention . Results Of the 190 practice s r and omized , 143 ( 75 % ) dental practice s provided follow-up data . Intervention practice s ’ mean performance improved post-intervention by 4 % on ASK ( 29 % baseline , adjusted odds ratio = 1.29 [ 95 % CI 1.17 - 1.42 ] ) , and by 11 % on ADVISE ( 44 % baseline , OR = 1.55 [ 95 % CI 1.28 - 1.87 ] ) . Control practice s improved by 3 % on ASK ( Adj . OR 1.18 [ 95 % CI 1.07 - 1.29 ] ) and did not significantly improve in ADVISE . A significant group-by-time interaction effect indicated that intervention practice s improved more over the study period than control practice s for ADVISE ( P = 0.042 ) but not for ASK . Conclusion This low-intensity , easily disseminated intervention was successful in improving provider performance on advice to quit . Trial Registration clinical trials.gov NCT00627185 ; http:// clinical trials.gov/ct2/show/NCT00627185 ( Archived by WebCite at http://www.webcitation.org/5c5Kugvzj BACKGROUND Community dental clinics are good setting s for smoking intervention . The aim here was to put forward a strategy for preventing adolescent smoking by means of a brief intervention . METHODS A total of 2,586 12-year-olds participated in this follow-up study . They were asked upon arrival for their annual routine dental examination to complete a smoking question naire and were r and omly assigned to either the intervention group or the usual care control group according to the last digit of their date of birth ( odd or even ) . The intervention comprised annually inquiring about smoking , showing photographs of the harmful effects of smoking on the teeth , allowing participants to examine their own mouth with a mirror , and finally counselling them in accordance with their answer to the question on smoking habits . The smoking status reported was not verified by other means . RESULTS The prevalence of smoking at the end of the 2-year follow-up was 18.1 % , in the intervention group and 20.8 % among the controls . However , no statistically significant differences between groups were found . CONCLUSIONS These results reflect the difficulties of achieving successful results with long-term smoking cessation programs with adolescents in unstable conditions To examine the effectiveness of advising patients who use tobacco to quit , the authors conducted a r and omized clinical trial to test a brief office-based intervention with all tobacco users in 75 fee-for-service dental practice s in Oregon . The authors found that the dental hygienist-delivered intervention was effective in getting smokeless tobacco users to quit at three and 12 months and to sustain abstinence at both three and 12 months . They found that the program was not effective for cigarette smokers . The authors discuss the public health implication s of program dissemination and widespread program adoption Ninety-eight cigarette smokers attending the Newcastle upon Tyne Dental Hospital , wishing to reduce their tobacco consumption , received smoking reduction advice in combination with dental health instruction and periodontal care . Those advised against smoking showed a greater reduction ( P < 0.001 ) in reported cigarette consumption during treatment and follow-up , compared with 38 control subjects who received dental health instruction but no advice against smoking . Fifty percent of intervention subjects reported reducing to half or less than half of their initial cigarette consumption , compared with 24 % for controls . Eighty percent of those advised against smoking reported some reduction , against 29 % for controls . The reported smoking cessation rate in the intervention group was 13.3 % , compared with 5.3 % in the control subjects . The results indicate that advice against smoking combined with dental health instruction and periodontal care can be an effective aid to reducing tobacco We describe a r and omized trial design ed to evaluate the effectiveness of a smokeless tobacco cessation intervention delivered by dental hygienists as part of a patient 's regularly scheduled cleaning visit . Seventy-five practice s were r and omized to continue their usual care ( n=25 ; 239 smokeless tobacco using patients enrolled ) or to receive training to provide a tobacco cessation intervention ( n=50 ; 394 smokeless tobacco using patients enrolled ) . Patient reports indicated that the training program was successful in getting hygienists to implement the intervention . The intervention produced a strong effect on sustained quitting for smokeless tobacco users but had no impact on secondary outcomes , including unsuccessful quit attempts , future intent to quit using smokeless tobacco , and change in readiness to quit using . Frequency of smokeless tobacco use and receipt of specific components of the intervention , including the video and written material s , predicted sustained cessation . Since this intervention was delivered by dental hygienists as part of a patient 's regularly scheduled cleaning visit , it is easily disseminable Cigarette smoking is a major risk factor for head and neck cancer , and individuals who continue to smoke past diagnosis and treatment are at elevated risk for further disease . In a r and omized controlled trial , a state of the art provider-delivered smoking cessation intervention was compared to a usual care advice control condition . The intervention consisted of surgeon- or dentist-delivered advice to stop smoking , a contracted quit date , tailored written material s , and booster advice sessions . Subjects were 186 patients with newly diagnosed first primary squamous cell carcinomas of the upper aerodigestive tract who had smoked cigarettes within the past year . At r and omization , 88.2 % of subjects were current smokers . At 12-month follow-up , 70.2 % of subjects completing the trial ( n = 114 ) were continuous abstainers ; among baseline smokers alone the continuous abstinence ( CA ) rate was 64.6 % . The cotinine validation rate at 12 months was 89.6 % . Modeling techniques were utilized in order to derive expected CA rates , which included noncompleter subjects ( n = 72 ) . The CA rate expected at 1 year for the entire patient population was 64.2 % , and for smokers alone the expected CA rate was 59.4 % . Logistic regression analysis carried out on baseline smokers identified predictors of 12-month CA status . These included medical treatment , stage of change , age , nicotine dependence , and race . The intervention effect was not significant , although the sign of the effect was positive . Based on these findings , we recommend systematic brief advice to stop smoking for head and neck cancer patients , with a stepped care approach for patients less able to quit Biochemical validation of smoking status has long been considered essential , but recent reports have question ed its utility in certain kinds of field trials . We describe efforts to biochemically vali date self-reports of smoking cessation from participants in four large-scale r and omized trials in outpatient clinics , hospitals , worksites , and dental clinics . These studies included over 5,000 adults smokers who participated in the population -based low-intensity intervention evaluations . At a 1-year follow-up , 798 subjects reported no tobacco use . We attempted to verify these reports using saliva continine/carbon monoxide validation procedures . Overall , there was a moderately high nonparticipation rate ( 27 % ) , a low disconfirmation rate ( 4 % ) , and a high self-reported relapse rate ( 12 % ) in the interval between survey and biochemical validation . There were no differences between intervention and control conditions on any of the above variables . Longer duration s of self-reported abstinence were strongly related to increased probability of biochemical confirmation . Differences in results across projects were related to how biochemical validation was conducted . These results , as well as statistical power considerations , raise questions about whether biochemical validation procedures are practical , informative , or cost-effective in such population -based , low-intensity intervention research A sample of private orthodontic practice s ( n = 40 ) from a controlled trial for clinician-initiated tobacco-use prevention was used to test the effectiveness of preventive medicine representative ( PMR ) visits in creating and maintaining an anti-tobacco office environment . Clinical staff of 20 offices , r and omly assigned to the experimental group , were trained by a PMR on the use of anti-tobacco material s ( no-smoking signs , posters , and print material s ) . Twenty control-group offices did not receive any training or special treatment . Subsequently , experimental-group offices were visited by a PMR once every three months and were telephoned six weeks after each visit over a 12-month period . During visits and phone calls , PMRs prompted offices to order anti-tobacco material s. Visits served to introduce offices to new material s and to encourage their continued use . Data from direct observations and self-report measures showed significant differences between experimental and control offices for display of anti-tobacco material s at 1.5 months and 12 months ( P < .001 ) . Results suggest that PMR visits may serve as an effective method of introducing and maintaining preventive medicine procedures in clinical environments SMILES PLUS was the first study to extend the clinician-delivered logic model to prevention of tobacco use among adolescents . This multi-site trial with 154 participating offices , based on social learning theory and a behavioral ecological model , was design ed to test whether orthodontists can prevent preteens from initiating smoking . The study found that orthodontists do not automatically adhere to anti-tobacco prevention services . Social learning variables can enhance both adherence to counseling guidelines and content of counseling to increase prevention effects . Providing financial incentives , tracking prescriptions , prompting positive feedback from patients , and adopting anti-tobacco counseling models in the office are likely to enhance anti-tobacco preventive services . Training orthodontists to be comfortable when advising nonsmoking youth not to start and to use social consequences to justify youth avoidance of tobacco might increase adherence to protocol s and make their counseling more powerful . Adolescent smokers prior to intervention were more likely to start other risky behaviors later . Preventing tobacco use may halt additional risk behaviors and thereby reduce morbidity/mortality even more than expected from tobacco control alone . New and refined clinical trials should be conducted to determine the most effective interventions for adolescent tobacco control by clinicians To investigate methods for improving and exp and ing the counseling of smokers by physicians and dentists , we assigned 112 physicians and 50 dentists ( in separate studies ) to one of the following conditions : the control or advice-only group received a one-hour lecture on the consequences and management of smoking and a booklet detailing a four-step protocol for counseling patients about smoking ; three other groups received , in addition , either , protocol reminder stickers placed on their patients ' charts ; nicotine gum made freely available to their patients ; or both chart reminders and nicotine gum . Exit interviews of 1,091 medical and 647 dental patients indicated that the presence of chart reminders and /or the availability of nicotine gum increased the time spent counseling and altered the nature of the smoking cessation counseling provided by both physicians and dentists This paper describes the aims , study design , and patient accrual and characteristics from an ongoing r and omized controlled trial evaluating a surgeon- and dentist-delivered smoking cessation intervention for head and neck cancer patients . Subjects ( n = 186 ) accrued into the trial are profiled in terms of demographics , medical and treatment descriptors , smoking history and behavior at enrollment , and related psychosocial variables ( mood , adherence indicators , and alcohol consumption ) . These patients have long histories of tobacco use , moderate to high levels of nicotine dependence , and a lack of overt mood disturbance and are receptive to behavioral change Sixteen colleges were matched on the baseline prevalence of spit tobacco ( ST ) use , and college pairs were r and omized , one to the intervention and the other to the control group . Baseball and football athletes at each intervention college received : an oral examination by a dental professional who pointed out ST-related problems in the athlete 's mouth and advised him to quit ST use ; counseling by a dental hygienist on strategies to cope with cravings and triggers for use ; and two follow-up telephone calls . At the three-month follow-up , quit rates were 24 % and 16 % for the intervention ( n = 171 ) and control ( n = 189 ) groups , respectively ( p < 0.05 ) . As the reported amount of ST used weekly increased , the percent of individuals who quit at 3 mos decreased ( p < 0.05 ) . Dental professionals appear to be effective in promoting spit tobacco cessation at 3 mos post-intervention in male college athletes , especially among those using lesser amounts of ST Background Tobacco is still the number one life style risk factor for ill health and premature death and also one of the major contributors to oral problems and diseases . Dentistry may be a potential setting for several aspects of clinical public health interventions and there is a growing interest in several countries to develop tobacco cessation support in dentistry setting . The aim of the present study was to assess the relative effectiveness of a high intensity intervention compared with a low intensity intervention for smoking cessation support in a dental clinic setting . Methods 300 smokers attending dental or general health care were r and omly assigned to two arms and referred to the local dental clinic for smoking cessation support . One arm received support with low intensity treatment ( LIT ) , whereas the other group was assigned to high intensity treatment ( HIT ) support . The main outcome measures included self-reported point prevalence and continuous abstinence ( ≥ 183 days ) at the 12-month follow-up . Results Follow-up question naires were returned from 86 % of the participants . People in the HIT-arm were twice as likely to report continuous abstinence compared with the LIT-arm ( 18 % vs. 9 % , p = 0.02 ) . There was a difference ( not significant ) between the arms in point prevalence abstinence in favour of the HIT- protocol ( 23 % vs. 16 % ) . However , point prevalence cessation rates in the LIT-arm reporting additional support were relatively high ( 23 % ) compared with available data assessing abstinence in smokers trying to quit without professional support . ConclusionS creening for willingness to quit smoking within the health care system and offering smoking cessation support within dentistry may be an effective model for smoking cessation support in Sweden . The LIT approach is less expensive and time consuming and may be appropriate as a first treatment option , but should be integrated with other forms of available support in the community . The more extensive and expensive HIT- protocol should be offered to those who are unable to quit with the LIT approach in combination with other support . Trial Registration Trial registration number : INTRODUCTION Military personnel are twice as likely as civilians to use smokeless tobacco ( ST ) . This study evaluated the efficacy of a minimal-contact ST cessation program in military personnel . METHODS Participants were recruited from 24 military dental clinics across the United States during annual dental examinations . Participants were 785 active-duty military personnel who were r and omly assigned to receive a minimal-contact behavioral treatment ( n = 392 ) or usual care ( n = 393 ) . The behavioral treatment included an ST cessation manual , a videotape cessation guide tailored for military personnel , and three 15-min telephone counseling sessions using motivational interviewing methods . Usual care consisted of st and ard procedures that are part of the annual dental examination , including recommendations to quit using ST and referral to extant local tobacco cessation programs . Participants were assessed at 3 and 6 months after enrollment . RESULTS Participants in the ST cessation program were significantly more likely to be abstinent from all tobacco , as assessed by repeated point prevalence at both 3 and 6 months ( 25.0 % ) , and were significantly more likely to be abstinent from ST use for 6 months , as assessed by prolonged abstinence ( 16.8 % ) , compared with participants in usual care ( 7.6 % and 6.4 % , respectively ) . DISCUSSION These results indicate that a minimal-contact behavioral treatment can significantly reduce ST use in military personnel and has the potential for widespread dissemination . If ST users were identified in dental visits and routinely referred to telephone counseling , this could have a substantial benefit for the health and well-being of military personnel Objectives : To assess the feasibility of using primary care dentists and the dental team providing smoking cessation advice in practice . Design : A prospect i ve study to examine the success of a smoking cessation programme . Setting : 54 primary care dental practice s in the UK . Method : Training and educational material s were supplied to members of the dental team and to potential recruits smoking 10 or more cigarettes a day . Recruitment was over 6 months and subjects were followed up for 9 months . In addition to dentists ' counselling , nicotine patches were made available , on request , at cost price . Salivary cotinine assay was used for validation of smoking levels at initial counselling and 9 months after recruitment . Results : 54 practice s were enrolled but only 22 recruited patients . Records of 154 eligible patients were evaluated . Compliance to attend follow up clinics was poor -- only 74 reported at 9 months . Among them 17 ( 11 % ) were successful in giving-up tobacco for 9 months as vali date d by patient histories and salivary cotinine assay . A large variation performance of the dental practice s was noted . Conclusions : Motivated dentists with staff support and access to information on smoking counselling are able to contribute to tobacco control measures in the community . The success of this programme closely parallels those reported in general medical practice setting s. In view of the very considerable attrition rates found at all levels of the programme in the present study and the uneven performance of the participating practice s the quit rate reported here may not accurately reflect what could be achieved in an individual primary care OBJECTIVES Primary care medical clinics are good setting s for smoking interventions . This study extends this strategy with a smokeless tobacco intervention delivered by dentists and dental hygienists in the course of routine dental care . METHODS Male users of moist snuff and chewing tobacco ( n = 518 ) were identified by question naire in clinic waiting rooms and then r and omly assigned to either usual care or intervention . The intervention included a routine oral examination with special attention to the part of the mouth in which tobacco was kept and an explanation of the health risks of using smokeless tobacco . After receiving unequivocal advice to stop using tobacco , each patient viewed a 9-minute videotape , received a self-help manual , and was briefly counseled by the dental hygienist . RESULTS Long-term success was defined as no smokeless tobacco use at both 3- and 12-month follow-ups , with those lost to follow-up counted as smokeless tobacco users . The intervention increased the proportion of patients who quit by about one half ( 12.5 % vs 18.4 % , P < .05 ) . CONCLUSIONS These results demonstrate the efficacy of a brief dental office intervention for the general population of smokeless tobacco users Identification of the cause of the development and progression of periodontitis has received extensive attention , with notable advances over the past decade in clinical , microbiological , immunological , biochemical , and behavioral knowledge . However , it is still largely unknown which factors lead to the conversion of non-destructive forms of periodontal disease into destructive forms and disease progression . Chronic adult periodontitis is believed to be influenced by an interaction of host defense and environmental factors . Although these variables have been studied extensively , no study has employed r and omized controlled prospect i ve human or r and omized controlled community intervention design s , method ologies necessary to prove a variable to be a cause of periodontitis . Owing to the absence of literature employing rigorous experimental design , this article assesses systematic ally observational , cross-sectional and longitudinal studies to examine the potential causal association between cigarette smoking and periodontitis . The methodology of Sir Bradford Hill 's criteria for causation was used as the framework . Results suggest that cigarette smoking is causally associated with periodontitis . That is , cigarette smoking is consistently associated with an increased prevalence/severity of periodontitis and is suspected on theoretical grounds of playing a causal role . Hill 's criteria provide a useful methodology to better underst and the pathogenesis of periodontal diseases and may be applied to study the pathogenesis of other dental diseases as well BACKGROUND Tobacco use is a leading cause of periodontitis and other oral diseases . Dental professionals can help patients quit , but few routinely offer tobacco cessation services , or TCS . In this article , the authors examine dental professionals ' attitudes toward offering TCS and patients ' attitudes toward receiving TCS from their dental offices . METHODS The authors used baseline data from a three-year r and omized controlled trial design ed to test the effectiveness of a dissemination strategy aim ed at increasing the proportion of tobacco users identified by the dental office , as well as the proportion of tobacco users advised to quit . Fifty-two dental offices in rural communities completed a question naire asking for demographic and professional information about their offices , usual TCS offered , barriers to providing TCS and their views on patient receptivity to TCS . A r and om sample of patients seen during one month were interviewed over the telephone about the TCS provided during their last visit and their comfort in receiving such services from their dental offices . RESULTS The authors found that 58.5 percent of the 3,088 dental patients surveyed believed that dental offices should provide TCS to patients . There was equal support among tobacco users and nonusers . Male patients ( 60.8 percent ) and younger patients ( 69.6 percent ) were more likely to believe that dental offices should provide TCS than were female patients ( 56.8 percent , P < .05 ) and older patients ( 57.3 percent , P < .05 ) . The authors also found that patients who had an interest in quitting were more likely to feel comfortable receiving TCS than were those patients who were not interested in quitting ( 59.7 percent vs. 39.4 percent , P < .01 ) . A total of 61.5 percent of dentists , however , thought patients did not expect such services . When dentists were asked about barriers to providing TCS , 94.3 percent listed patient resistance as a barrier , and 53.9 percent were concerned that patients would leave their practice s. CONCLUSIONS The authors found a wide discrepancy between patients ' and dental professionals ' views on TCS . A total of 58.5 percent of patients believe dentists routinely should offer such services , while 61.5 percent of dental professionals believed patients did not expect TCS . Patients who were interested in quitting felt more comfortable receiving quit advice . CLINICAL IMPLICATION S Periodontitis and other oral diseases are linked directly to tobacco use . Advising patients to quit is a professional responsibility . Tobacco users expect and are comfortable receiving such advice . It is up to dental professionals to overcome their concerns about patient receptivity and provide these services OBJECTIVES The objectives of this study are to design and implement a system-level tobacco-control intervention in a large prepaid dental group practice and assess effects on staff performance measures and patient satisfaction . METHODS We matched 14 dental facilities on size , socioeconomic status , smoking rate , and periodontal status , and then r and omly assigned them to intervention or usual-care control . We trained intervention staff in an " Assisted Referral " team approach for assessing tobacco use , providing tailored advice and brief counseling , and encouraging smokers to talk by telephone with a specially trained tobacco counselor . Patients could call from the office or ask that the counselor call them later . Telephone counselors helped patients explore motivations and barriers for quitting ; review available cessation-support strategies , programs , and medications ; and identify next steps . RESULTS During the 14-month study period , 66,516 members had annual- or new-patient examinations . Both intervention and control sites had high rates of tobacco assessment ( 97 percent ) and advice ( 93 percent ) . Intervention patients were more likely than controls ( 69 percent versus 3 percent , P < 0.01 ) to receive additional chair-side tobacco counseling and assistance , and 11 percent agreed to receive additional telephone counseling . Intervention patients were more satisfied than controls with the dental team 's tobacco-control efforts ( P < 0.03 ) . Referral rates varied substantially for different staff . CONCLUSIONS The Assisted Referral approach was successfully integrated into routine dental care , was well received by patients , and result ed in increased patient satisfaction . Because free telephone-based tobacco counseling is now available nationwide , the approach may be a practical strategy for most dental-care setting This study evaluated 2 methods of disseminating an empirically vali date d smokeless tobacco intervention delivered during routine dental care . Twenty cities within 12 states were stratified and then r and omized to 1 of 3 groups : personalized instruction ( PI ) , self- study ( SS ) , or delayed training ( DT ) control . Dental hygienists in the SS condition were sent a manual and video . Those in the PI condition were recruited to attend a workshop . Thirty-seven percent of eligible hygienists agreed to participate . At 12 months postenrollment , hygienists in the SS and PI conditions significantly increased their " Assist " behaviors ( discuss cessation techniques , help patient set a quit date , and provide cessation material s ) and reported fewer perceived barriers to delivering the intervention as compared with hygienists in DT . An economic analysis suggests that SS is more cost-effective than PI The purpose of this research was to explore the changes that occurred in dental students ' counseling techniques as a result of training in Brief Motivational Interviewing ( BMI ) . A r and omized pretest , posttest design was used with eleven students in each group . Baseline and posttraining measures of students ' counseling techniques and the characteristics of the counseling session with st and ardized patients were made . The measures were : student behavior from videotapes , patient involvement in the treatment , establishment of good doctor-patient rapport , perceived efficacy in promoting patient change , and student confidence and interest in the task . MANOVA found significant differences between the trained and the untrained groups ( F = 4.019 , p = 0.018 ) . Training result ed in sessions in which students used more BMI techniques and patients were more actively involved . No changes were seen in the other variables . Future studies must examine whether more experience will improve the students ' ability to use BMI to enhance patient rapport , to increase their sense of competence and interest in doing counseling , and to determine the effectiveness of the counseling to encourage patient smoking cessation BACKGROUND Public health dental clinic patients use tobacco at disproportionately high rates . The purpose of this study was to evaluate a tobacco-use cessation program delivered via public health dental practitioners . METHODS Two public health dental clinics participated in this quasiexperimental design study . First , all patients in one clinic who used tobacco ( n = 178 ) received usual care . Next , the authors trained all practitioners to conduct a tobacco-use assessment and provide a brief cessation intervention . Subsequently , all patients in both clinics who used tobacco ( N = 190 ) received the intervention . All enrolled patients had an income at or below the federal poverty level . The authors conducted follow-up assessment s at six weeks and three and six months after enrollment . RESULTS Differences in self-reported quitting by condition between participants in the two groups were significant across all endpoints . Patients in the intervention group were more likely to quit than those receiving usual care ( 15.5 versus 4.3 percent ) and after 12 months ( 18.8 versus 4.6 percent ) . Controlling for enrollment differences between patients in the two groups ( age , race/ethnicity , time to first cigarette after waking ) , the authors found that differences between groups were significant for quitting at three months ( P < .05 ; odds ratio [ OR ] = 4.85 ; 95 percent confidence interval [ CI ] = 1.20 , 19.60 ) , and six months ( P < . 01 ; OR = 5.25 ; 95 percent CI = 1.35 , 20.36 ) . CONCLUSIONS The results of this study suggest the viability and effectiveness of delivering a tobacco intervention to low-income smokers via public dental practitioners . A r and omized clinical trial is warranted . CLINICAL IMPLICATION S The potential reach of public health dental clinics is great . Because of the high percentage of tobacco-using patients in these clinics , the public health impact of a program such as the one reported here would be significant OBJECTIVE To determine the efficacy of a spit tobacco ( ST ) intervention design ed to promote ST cessation and discourage ST initiation among male high school baseball athletes . METHODS This study was a cluster-r and omized controlled trial . Forty-four r and omly selected high schools in rural California were r and omized within strata ( prevalence of ST use and number and size of baseball teams ) to either the intervention or the control group . Ninety-three percent of eligible baseball athletes participated , yielding 516 subjects in 22 intervention schools and 568 subjects in 22 control schools . Prevalences of sustained ST cessation and ST use initiation over 1 year were assessed by self-report . Multivariate logistic regression models for clustered responses were used to test the null hypotheses of no association between group and the two outcomes , adjusted for the stratified design and baseline imbalances between groups in significant predictors of ST use . RESULTS Prevalence of cessation was 27 % in intervention high schools and 14 % in control high schools ( odds ratio (OR)=2.29 ; 95 % confidence interval ( CI ) , 1.36 - 3.87 ) . The intervention was especially effective in promoting cessation among those who , at baseline , lacked confidence that they could quit ( OR=6.4 ; 95 % CI , 1.0 - 4.3 ) , among freshmen ( OR=15 ; 95 % CI , 0.9 - 260 ) , and among nonsmokers ( OR=3.2 ; 95 % CI , 0.9 - 11 ) . There was no significant difference between groups in the prevalence of ST initiation . CONCLUSIONS This intervention was effective in promoting ST cessation , but was ineffective in preventing initiation of ST use by nonusers A double-blind clinical trial was conducted to determine whether the use of a chewing gum containing 2.0 mg nicotine ( as an adjunct to a stop-smoking program ) had any effects upon oral health . A total of 193 adults who smoked cigarettes volunteered with informed consent , were given routine dental prophylaxes , and were examined for the presence of plaque , stained pellicle , gingivitis , calculus , and general oral pathosis . The subjects were then r and omly assigned to use either a nicotine-containing or a placebo chewing gum . After 15 weeks the subjects were recalled and re-examined . Smoking cessation was determined through question naire and analysis of the carbon monoxide content of alveolar air . At the completion of the study , 79 subjects had used the placebo gum and 78 had used the nicotine gum . Data analysis indicated that the nicotine chewing gum had no significant influence on any of the oral health parameters grade d , as compared to the placebo gum . The continuation of smoking , however , was associated with significant increases in gingivitis and calculus rates OBJECTIVE Disseminating effective interventions to health care professionals is a critical step in ensuring that patients receive needed advice and material s. This cost effectiveness analysis compared two methods of disseminating an effective protocol for smokeless tobacco cessation intervention . METHOD Interested dental hygienists ( N = 1051 ) were recruited in 20 Western and Midwestern U.S. communities and r and omized by community to receive workshop training , self- study with mailed material s , and delayed self- study training , in 1996 - 98 . Hygienists were surveyed about their smokeless tobacco-related activities with patients at baseline and post-intervention . Data on intervention costs were collected , and incremental costs per unit of behavior change were calculated . RESULTS Self- study was more cost effective than workshop training under a wide range of assumptions : change in group versus individual behavior , hygienists ' time and travel costs included or excluded , and hygienist wage rates at the national median or substantially lower . However , workshops may be as cost effective in producing behavior change among hygienists earning wages substantially higher than the national median . CONCLUSION Self- study may be a more cost effective method than workshops to achieve behavior change among motivated health professionals BACKGROUND Time and re source constraints limit the ability of oral health care professionals to help patients quit smoking . Opportunities exist for dental providers to help patients who smoke by enrolling them in tobacco use quitlines . The authors conducted a pilot study to investigate whether such referrals were feasible and effective . METHODS The authors r and omly assigned eight general dental practice s to provide either brief counseling regarding smoking cessation or brief counseling along with referrals to a tobacco use quitline for patients receiving routine dental hygiene care who reported that they were currently smoking cigarettes . RESULTS The authors enrolled 82 patients ( 60 in the tobacco use quitline group , 22 in the brief counseling group ) . At six months , the self-reported , seven-day point prevalence tobacco use abstinence rates were 25.0 percent ( 15 of 60 patients ) in the tobacco use quitline group and 27.3 percent ( six of 22 patients ) in the brief-counseling group ( P approximately 1.0 ) . Twenty-eight ( 47 percent ) of 60 subjects in the tobacco use quitline group completed the initial tobacco use quitline consultation . Abstinence rates among subjects in the quitline group were higher if they completed more telephone consultations . CONCLUSIONS Referral to a tobacco use quitline by dental practice s is a feasible strategy for helping patients quit smoking if efficient links between the dental practice and the tobacco use quitline can be established . Research is needed to evaluate whether it is more effective than st and ard clinical interventions for tobacco use cessation . CLINICAL IMPLICATION S Dental practitioners with limited time and other re sources can assist patients who smoke by referring them to a tobacco use quitline The National Cancer Institute 's program to help dentists reduce tobacco use among their patients is part of the Community Intervention Trial for Smoking Cessation , a 22-community , r and omly controlled trial of an intervention program for smoking cessation . Results of COMMIT baseline surveys of dentists in the 11 intervention communities are presented This study was design ed to compare various salivary parameters between smokers and non-smokers and to determine the influence of a nicotine-containing chewing gum ( used to aid in quit-smoking efforts ) upon these same parameters . At the baseline examination , subjects were assigned to one of three groups : non-smokers who did not utilize any gum , smokers provided a nicotine-containing gum , and smokers provided a placebo gum . Saliva was collected from all subjects and analyzed for acidogenicity and buffer pH as well as for levels of thiocyanate , lactoperoxidase , lysozyme , lactoferrin , and secretory IgA. After 15 weeks of gum usage , saliva was again collected from each subject and the identical analyses performed . Significant differences were observed between smokers and non-smokers with regard to three parameters : The saliva of smokers contained greater concentrations of thiocyanate and lower concentrations of lactoferrin , at the baseline examination and after the 15-week test period . In addition , the CO content of alveolar air was higher in smokers at both examination periods . In contrast , the use of the nicotine gum per se had no effect on any of the test parameters Study aim was to determine the influence of a patient information leaflet ( PIL ) on mouth cancer to improve knowledge , reduce distress and increase intention to accept a mouth screen over a 2-month period . The design was a r and omised controlled trial . Two dental practice s in the northwest of Engl and participated . St and ardised multi-item scales of the three outcome measures were employed . The PIL was given to a r and omised intervention group of patients in waiting room . Single sheet question naire was completed by both groups of patients at baseline in waiting room ( immediately following leaflet administration in intervention arm of study ) . Repeat question naire completion at 8 weeks by all patients through postal system . Mann-Whitney U-tests comparing outcome variables between patients with and without access to the leaflet at baseline and 8 weeks were performed . Multiple logistic regression was used to predict re-reading of the leaflet at home . Useable replies were received from 317 patients ( 60 % response rate ) . All measures showed some benefit of immediate exposure to the leaflet at follow up . Older patients , less initial knowledge , and self-reported smoking positively predicted the re-reading of the leaflet . The introduction of a mouth cancer PIL into dental practice may help to inform patients about oral cancer , moderate distress and encourage acceptance of an oral health screen Fifty private practitioners and their office staff members were r and omly assigned to one of four groups : participants received a protocol for smoking management and a lecture on the consequences and management of smoking , or in addition , had nicotine gum freely available to patients , had stickers attached to their charts , or had gum and reminders . The percentage of patients in each group who had quit smoking a year later was 7.7 , 16.3 , 8.6 , and 16.9 , respectively , indicating a significant main effect for the gum conditions . The availability of nicotine gum also significantly increased the amount of time that patients reported they received smoking cessation counseling from the dentists and office staff OBJECTIVES The purpose of this study was to determine the efficacy of a college-based smokeless tobacco cessation intervention targeting college athletes . METHODS Sixteen colleges were matched for prevalence of smokeless tobacco use in their combined baseball and football teams and r and omly assigned within college pairs to the intervention or the control group . One-year prevalence of cessation among smokeless tobacco users was determined by self-report of abstinence for the previous 30 days . Differences between groups were analyzed in a weighted version of the Fisher 1-sided permutation test for paired sample s after adjustment for significant predictors of quitting other than the intervention ( i.e. , smokeless tobacco uses per week and most frequently used br and ) . RESULTS Cessation prevalences were 35 % in the intervention colleges and 16 % in the control colleges when subjects with unknown quit status were defined as nonquitters . After adjustment for other significant predictors of quitting , the difference of 19 % increased to 21 % . The intervention effect increased with level of smokeless tobacco use . CONCLUSIONS This intervention was effective in promoting smokeless tobacco cessation , especially among those who were more frequent users OBJECTIVES We sought to compare the effectiveness of a dental practitioner advice and brief counseling intervention to quit tobacco use versus usual care for patients in community health centers on tobacco cessation , reduction in tobacco use , number of quit attempts , and change in readiness to quit . METHODS We r and omized 14 federally funded community health center dental clinics that serve diverse racial/ethnic groups in 3 states ( Mississippi , New York , and Oregon ) to the intervention ( brief advice and assistance , including nicotine replacement therapy ) or usual care group . RESULTS We enrolled 2549 smokers . Participants in the intervention group reported significantly higher abstinence rates at the 7.5-month follow-up , for both point prevalence ( F(1,12 ) = 6.84 ; P < .05 ) and prolonged abstinence ( F(1,12 ) = 14.62 ; P < .01 ) than did those in the usual care group . CONCLUSIONS The results of our study suggest the viability and effectiveness of tobacco cessation services delivered to low-income smokers via their dental health care practitioner in community health centers . Tobacco cessation services delivered in public dental clinics have the potential to improve the health and well-being of millions of Americans The use of a chewing gum containing nicotine as an adjunct to a behavior modification smoking-cessation program increased the number of smokers who successfully discontinued smoking Helping patients to quit smoking is in the interest of all health professionals , including dentists . This chewing gum may be able to help There is increasing interest in broadly inclusive public health interventions that involve low-cost , self-help material s and minimal support from professionals . Dental health care workers ( DHCWs ) are a largely untapped re source for providing advice and brief counseling to tobacco-using patients , and there are good reasons to believe that they can be effective in this role . The results of our r and omized clinical trials have shown that a brief dental office-based intervention can be effective in helping smokeless tobacco users to quit and smokers to reduce their use and become more ready to quit . A third clinical trial tested the effectiveness of two methods of disseminating the smokeless tobacco intervention to DHCWs throughout the western United States . Workshops were more effective than self- study in effecting behavior change , although our analyses indicate that self- study was more cost-efficient . These studies have demonstrated the viability of using dentists and dental hygienists to provide brief cessation advice and supportive material s in the context of regular oral health visits to encourage their patients to quit . The results of these studies also support the timeliness of further dissemination and diffusion of this program to practitioners , dental schools , and dental hygiene programs BACKGROUND The Ask , Advise , Refer ( AAR ) model of intervening with patients who use tobacco promotes a brief office-based intervention plus referral to a tobacco quitline . However , there is little evidence that this model is effective . The primary aim of this study was to evaluate the effects on patients ' tobacco use of two levels of a dental office-based intervention compared with usual care . METHODS The authors r and omly assigned 68 private dental clinics to one of three conditions : 5 As ( Ask , Advise , Assess , Assist , Arrange ) ; 3 As ( AAR model ) ; or usual care , and they enrolled 2,160 participants . RESULTS At the 12-month assessment , compared with those in usual care , participants in the two intervention conditions combined were more likely to report cessation of tobacco use , as measured by nine-month prolonged abstinence ( 3 percent versus 2 percent ; F(1,66 ) = 3.97 , P < .10 ) and 12-month point prevalence ( 12 percent versus 8 percent ; F(1,66 ) = 7.32 , P < .01 ) . There were no significant differences between participants in the clinics using the 5 As and 3 As strategies . CONCLUSIONS The results of this study are inconclusive as to whether referrals to a quitline add value to brief dental office-based interventions . Patients receiving telephone counseling quit tobacco use at higher rates , but only a small percentage of those proactively referred actually received counseling . CLINICAL IMPLICATION S The results confirm those of previous research : that training dental practitioners to provide brief tobacco-use cessation advice and assistance results in a change in their behavior , and that these practitioners are effective in helping their patients to quit using tobacco BACKGROUND The authors conducted this study to ascertain the feasibility of face-to-face educational outreach visits , also called " academic detailing , " as a methodology to promote dentists ' adoption and incorporation of tobacco-use cessation counseling activities into their practice s. METHODS The authors obtained a sampling frame of one dental health maintenance organization 's , or DHMO 's , enrolled dentists who practice d in one of four Northeastern states and who had more than 300 DHMO patients . Of 507 eligible dentists , 88 agreed to participate , and the authors r and omly assigned them to either intervention ( an academic detailing program ) or control ( practice as usual ) conditions . Changes in practice behaviors over time were obtained by question naires . The authors used descriptive statistics to analyze data using a statistics software package . RESULTS Only 9 percent of dentists who agreed to participate had received any training in decreasing patients ' tobacco use . The authors associated the dentists ' staff members ' considerable resistance to the detailing program with issues such as having to deal with additional paperwork and uncooperative patients , the perception that only a few patients use tobacco and that counseling does not work . Many dentists also expressed concern about their lack of tobacco-use cessation knowledge . Overall , dentists ' resistance to detailing decreased with follow-up detailing visits . CONCLUSIONS It is feasible to increase and incorporate tobacco-use cessation counseling in dental offices . However , significant barriers must be surmounted first if this goal is to be achieved by use of academic detailing . CLINICAL IMPLICATION S Using academic detailing , dentists can be effective agents in increasing the longevity , decreasing the morbidity and improving the oral health status of their patients through the promotion of smoking cessation Context : Athletes in the United States are at high risk for using spit ( smokeless ) tobacco ( ST ) and incurring its associated adverse health effects . Objective : To examine whether an athletic trainer-directed ST intervention could decrease initiation and promote cessation of ST use among male collegiate baseball athletes . Design : Stratified , cluster-r and omized controlled trial . Setting : Fifty-two California colleges . Patients or Other Participant(s ) : A total of 883 subjects in 27 intervention colleges and 702 subjects in 25 control colleges participated , as did 48 certified athletic trainers . Intervention(s ) : For college athletic trainers and associated dental professionals , a 3-hour video conference , and for collegiate athletes , an oral cancer screening with feedback and brief counseling during the preseason health screenings , athletic trainer support for cessation , and a peer-led educational baseball team meeting . Main Outcome Measure(s ) : The subjects ' ST use over 1 year was assessed by self-report . At the end of the study , the certified athletic trainers were mailed a survey assessing their tobacco use and perceptions and behavior related to tobacco control in the athletic environment . We used multivariable logistic regression models for clustered responses ( generalized estimating equations ) to test the difference between groups in ST-use initiation and cessation and to identify significant overall predictors of noninitiation and cessation of ST use . Results : Of the 1585 athletes recruited , 1248 ( 78.7 % ) were followed up at 12 months . In addition , 48 of the 52 athletic trainers ( 92 % ) responded to the 1-year follow-up survey . The ST-use initiation ( incidence ) was 5.1 % in intervention colleges and 8.4 % in control colleges ( generalized estimating equation odds ratio = 0.58 , 95 % confidence interval = 0.35 - 0.99 ) . Predictors of ST noninitiation were low lifetime tobacco and monthly alcohol use ( odds ratio = 1.98 , 95 % confidence interval = 1.40- 2.82 ) and athletic trainers ' report that the baseball coach supported ST-use prevention activities ( odds ratio = 1.43 , 95 % confidence interval = 1.11 - 1.83 ) . Although at 1 year , cessation of ST use was relatively high in both groups ( 36 % ) , we noted no significant difference between the groups ( odd ratio = 0.94 , 95 % confidence interval = 0.70 - 1.27 ) . Conclusions : The intervention was significantly effective in preventing incident ST use but did not significantly increase cessation beyond that seen in the control group . The latter finding is inconsistent with previous studies and may be explained by spillover of the intervention to control colleges , other anti-tobacco activity in control colleges , and /or the small sample of dependent ST users enrolled in the study |
12,408 | 27,906,836 | Conclusion : In summary , among the wide heterogenetic population , modest associations between VVV of SBP and all-cause mortality , CVD incidence , CVD mortality , CHD incidence , and stroke incidence were found . | Objective : Clinical cohort studies have reported that visit-to-visit variability ( VVV ) of blood pressure ( BP ) is associated with cardiovascular disease ( CVD ) or mortality .
However , the results were not consistent in all studies .
The current study is , therefore , aim ed to conduct a systematic review and meta- analysis to determine the association between VVV of BP and CVD and all-cause mortality . | Background — Recent evidence suggests that visit-to-visit variability in systolic blood pressure ( SBP ) and maximum SBP are predictors of cardiovascular disease . However , it remains uncertain whether these parameters predict the risks of macrovascular and microvascular complications in patients with type 2 diabetes mellitus . Methods and Results — The Action in Diabetes and Vascular Disease : Preterax and Diamicron Modified Release Controlled Evaluation ( ADVANCE ) was a factorial r and omized controlled trial of blood pressure lowering and blood glucose control in patients with type 2 diabetes mellitus . The present analysis included 8811 patients without major macrovascular and microvascular events or death during the first 24 months after r and omization . SBP variability ( defined as st and ard deviation ) and maximum SBP were determined during the first 24 months after r and omization . During a median 2.4 years of follow-up from the 24-month visit , 407 major macrovascular ( myocardial infa rct ion , stroke , or cardiovascular death ) and 476 microvascular ( new or worsening nephropathy or retinopathy ) events were observed . The association of major macrovascular and microvascular events with SBP variability was continuous even after adjustment for mean SBP and other confounding factors ( both P<0.05 for trend ) . Hazard ratios ( 95 % confidence intervals ) for the highest tenth of SBP variability were 1.54 ( 0.99–2.39 ) for macrovascular events and 1.84 ( 1.19–2.84 ) for microvascular events in comparison with the lowest tenth . For maximum SBP , hazard ratios ( 95 % confidence intervals ) for the highest tenth were 3.64 ( 1.73–7.66 ) and 2.18 ( 1.04–4.58 ) , respectively . Conclusion — Visit-to-visit variability in SBP and maximum SBP were independent risk factors for macrovascular and microvascular complications in type 2 diabetes mellitus . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique Identifier : NCT00145925 To assess the prognostic significance of blood pressure ( BP ) variability , we followed health outcomes in a family-based r and om population sample representative of the general population ( n=2944 ; mean age : 44.9 years ; 50.7 % women ) . At baseline , BP was measured 5 times consecutively at each of 2 home visits 2 to 4 weeks apart . We assessed within-subject overall ( 10 readings ) , within- and between-visit systolic BP variability from variability independent of the mean , the difference between maximum and minimum BP , and average real variability . Over a median follow-up of 12 years , 401 deaths occurred and 311 participants experienced a fatal or nonfatal cardiovascular event . Overall systolic BP variability averaged ( SD ) 5.45 ( 2.82 ) units , 15.87 ( 8.36 ) mmHg , and 4.08 ( 2.05 ) mmHg for variability independent of the mean , difference between maximum and minimum BP , and average real variability , respectively . Female sex , older age , higher-mean systolic BP , lower body mass index , a history of peripheral arterial disease , and use of & bgr;-blockers were the main correlates of systolic BP variability . In multivariable-adjusted analyses , overall and within- and between-visit BP variability did not predict total or cardiovascular mortality or the composite of any fatal plus nonfatal cardiovascular end point . For instance , the hazard ratios for all cardiovascular events combined in relation to overall variability independent of the mean , difference between maximum and minimum BP , and average real variability were 1.05 ( 0.96–1.15 ) , 1.06 ( 0.96–1.16 ) , and 1.08 ( 0.98–1.19 ) , respectively . By contrast , mean systolic BP was a significant predictor of all end points under study , independent of BP variability . In conclusion , in an unbiased population sample , BP variability did not contribute to risk stratification over and beyond mean systolic BP Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects , but relevant data for older individuals are sparse . We analysed data from the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) study of 5804 participants aged 70–82 years with a history of , or risk factors for cardiovascular disease . Visit-to-visit variability in blood pressure ( st and ard deviation ) was determined using a minimum of five measurements over 1 year ; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up ; longer-term follow-up ( mean 7.1 years ) was available for 1808 subjects . Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality ( hazard ratio per 5 mmHg increase in st and ard deviation of systolic blood pressure = 1.2 , 95 % confidence interval 1.1–1.4 ; hazard ratio 1.1 , 95 % confidence interval 1.1–1.2 , respectively ) . Variability in diastolic blood pressure associated with increased risk for coronary events ( hazard ratio 1.5 , 95 % confidence interval 1.2–1.8 for each 5 mmHg increase ) , heart failure hospitalisation ( hazard ratio 1.4 , 95 % confidence interval 1.1–1.8 ) and vascular ( hazard ratio 1.4 , 95 % confidence interval 1.1–1.7 ) and total mortality ( hazard ratio 1.3 , 95 % confidence interval 1.1–1.5 ) , all in long-term follow-up . Pulse pressure variability was associated with increased stroke risk ( hazard ratio 1.2 , 95 % confidence interval 1.0–1.4 for each 5 mmHg increase ) , vascular mortality ( hazard ratio 1.2 , 95 % confidence interval 1.0–1.3 ) and total mortality ( hazard ratio 1.1 , 95 % confidence interval 1.0–1.2 ) , all in long-term follow-up . All associations were independent of respective mean blood pressure levels , age , gender , in-trial treatment group ( pravastatin or placebo ) and prior vascular disease and cardiovascular disease risk factors . Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects Visit-to-visit blood pressure variability ( VTV-BPV ) is an independent risk factor for cardiovascular events and death in the general population . We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis , using data from a National Institutes of Health-sponsored r and omized trial ( the HEMO study ) . We used the coefficient of variation ( CV ) and the average real variability in systolic blood pressure ( SBP ) as metrics of VTV-BPV . In all , 1844 out of 1846 r and omized subjects had at least three visits with SBP measurements and were included in the analysis . Median follow-up was 2.5 years ( interquartile range 1.3–4.3 years ) , during which time there were 869 deaths from any cause and 408 ( adjudicated ) cardiovascular deaths . The mean pre-dialysis SBP CV was 9.9±4.6 % . In unadjusted models , we found a 31 % higher risk of death from any cause per 10 % increase in VTV-BPV . This association was attenuated after multivariable adjustment but remained statistically significant . Similarly , we found a 28 % higher risk of cardiovascular death per 10 % increase in VTV-BPV , which was attenuated and no longer statistically significant in fully adjusted models . The associations among VTV-BPV , death and cardiovascular death were modified by baseline SBP . In a diverse , well-dialyzed cohort of patients on maintenance hemodialysis , VTV-BPV , assessed using metrics of variability in pre-dialysis SBP , was associated with a higher risk of all-cause mortality and a trend toward higher risk of cardiovascular mortality , particularly in patients with a lower baseline SBP Objective To investigate whether baseline systolic blood pressure variability was a risk factor for stroke , cardiovascular mortality or cardiac events during the Syst-Eur trial . Design The Syst-Eur study was a r and omized , double-blind , placebo-controlled trial , powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo . Systolic blood pressure variability measurements were made on 744 participants at the start of the trial . Systolic blood pressure variability was calculated over three time frames : 24 h , daytime and night-time . The placebo and active treatment subgroups were analysed separately using an intention-to-treat principle , adjusting for confounding factors using a multiple Cox regression model . Participants An elderly hypertensive European population . Main outcome measures Stroke , cardiac events ( fatal and non-fatal heart failure , fatal and non-fatal myocardial infa rct ion and sudden death ) and cardiovascular mortality ( death attributed to stroke , heart failure , myocardial infa rct ion , sudden death , pulmonary embolus , peripheral vascular disease and aortic dissection ) . Results The risk of stroke increased by 80 % ( 95 % confidence interval : 17–176 % ) for every 5 mmHg increase in night-time systolic blood pressure variability in the placebo group . Risk of cardiovascular mortality and cardiac events was not significantly altered . Daytime variability readings did not predict outcome . Antihypertensive treatment did not affect systolic blood pressure variability over the median 4.4-year follow-up . Conclusion In the placebo group , but not the active treatment group , increased night-time systolic blood pressure variability on admission to the Syst-Eur trial was an independent risk factor for stroke during the trial Objective : To assess how visit-to-visit variability of SBP correlates with systemic atherosclerotic change and various prognoses . Background : Visit-to-visit SBP variability correlates with cardiovascular events . However , the mechanisms underlying the impact of visit-to-visit SBP variability on prognoses are poorly understood . Methods and results : A total of 485 patients with essential hypertension from the Non-Invasive Atherosclerotic Evaluation in Hypertension ( NOAH ) study cohort were included . We analyzed the correlation between visit-to-visit SBP variability and multiple clinical parameters . Next , we prospect ively examined the correlation of SBP variability and frequency of cardiovascular disease ( CVD ) and total mortality . Patients with higher SBP variability exhibited significantly higher rates of statin use , as well as higher pulse wave velocity ( PWV ) , left-ventricular mass index ( LVMI ) , plaque score , and resistive index of the common carotid artery ; these patients also exhibited lower estimated glomerular filtration rate . Kaplan – Meier analysis demonstrated that patients with higher SBP variability have a significantly higher incidence of CVD and mortality rate . The hazard ratio of SBP variability for incidence of CVD was greatly diminished after adjustment for intima – media thickness , plaque score , and resistive index , and was slightly diminished after adjustment for PWV and LVMI . Visit-to-visit SBP variability remained an independent risk factor for mortality after adjustment . Conclusion : Visit-to-visit SBP variability correlates significantly with systemic atherosclerotic change , incidence of CVD , and mortality rate . Altered arterial functions , such as macrovascular atherosclerosis and vascular resistance , are responsible for the correlations between visit-to-visit SBP variability and incidence of CVD Introduction : Fluorescence in situ hybridization ( FISH ) is currently the st and ard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged ( ALK+ ) lung cancers for ALK inhibitor therapies . ALK immunohistochemistry ( IHC ) may serve as a screening and alternative diagnostic method . The Canadian ALK ( CALK ) study was initiated to implement a multicenter optimization and st and ardization of laboratory developed ALK IHC and FISH tests across 14 hospitals . Methods : Twenty-eight lung adenocarcinomas with known ALK status were used as blinded study sample s. Thirteen laboratories performed IHC using locally developed staining protocol s for 5A4 , ALK1 , or D5F3 antibodies ; results were assessed by H-score . Twelve centers conducted FISH using protocol s based on Vysis ’ ALK break-apart FISH kit . Initial IHC results were used to optimize local IHC protocol s , followed by a repeat IHC study to assess the results of st and ardization . Three laboratories conducted a prospect i ve parallel IHC and FISH analysis on 411 consecutive clinical sample s using post-validation optimized assays . Results : Among study sample s , FISH demonstrated 22 consensus ALK+ and six ALK wild type tumors . Preoptimization IHC scores from 12 centers with 5A4 and the percent abnormal cells by FISH from 12 centers showed intraclass correlation coefficients of 0.83 and 0.68 , respectively . IHC optimization improved the intraclass correlation coefficients to 0.94 . Factors affecting FISH scoring and outliers were identified . Post-optimization concurrent IHC/FISH testing in 373 informative cases revealed 100 % sensitivity and specificity for IHC versus FISH . Conclusions : Multicenter st and ardization study may accelerate the implementation of ALK testing protocol s across a country/region . Our data support the use of an appropriately vali date d IHC assay to screen for ALK+ lung cancers BACKGROUND Blood pressure ( BP ) variability ( BPV ) is a novel risk factor for the development of atherosclerotic diseases . High BPV has recently been shown to predict all-cause and cardiovascular mortality in patients with lacunar infa rct . Whether BPV has prognostic implication s in patients with ischemic stroke subtypes , other than those due to small-vessel occlusion , remains uncertain . METHODS We prospect ively followed up the clinical outcome of 632 consecutive ischemic stroke patients without atrial fibrillation . The average BP and BPV , as determined by the coefficient of variation of the systolic and diastolic BP , were recorded during a mean 12 ± 6 outpatient clinic visits . RESULTS The average age of the population was 71 ± 11 years . After a mean of 76 ± 18 months of follow-up , 161 patients died ( 26 % ) ; 35 % ( n = 56 of 161 ) of these deaths were due to cardiovascular causes . Sixteen percent and 5 % developed recurrent stroke and acute coronary syndrome ( ACS ) , respectively . After adjusting for mean systolic BP and confounding variables , patients with high systolic BPV were at significantly greater risk of cardiovascular mortality ( hazards ratio ( HR ) = 2.36 ; 95 % confidence interval ( CI ) = 1.02 - 5.49 ; P < 0.05 ) . High systolic BPV also predicted all-cause mortality after adjusting for mean systolic BP ( HR = 1.79 ; 95 % CI = 1.16 - 2.75 ; P < 0.05 ) . There was no association between systolic BPV and nonfatal recurrent stroke or nonfatal ACS . Raised diastolic BPV did not predict recurrent nonfatal stroke , nonfatal ACS , or mortality . CONCLUSIONS Visit-to-visit systolic BPV predicts long-term all-cause and cardiovascular mortality in patients with ischemic stroke without atrial fibrillation , independent of other conventional risk factors , including average BP control BACKGROUND AND OBJECTIVES Increased systolic BP visit-to-visit variability ( SBV ) may be associated with higher overall mortality and cardiovascular events . However , few studies have examined these associations in patients with CKD , and the relation of SBV with CKD progression and ESRD has not been shown . This study analyzed the association of SBV with overall mortality , cardiovascular mortality , cardiovascular events , and renal events among individuals enrolled in the African American Study of Kidney Disease ( AASK ) trial . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This was a prospect i ve observational study of 908 participants during the trial phase of the AASK study , with at least 1 year of BP measurements available and followed for 3 - 6.4 years . SBV was calculated as the SD of the systolic pressure from five visits occurring 3 - 12 months after r and omization . The association of SBV with risk of overall mortality , cardiovascular mortality , a composite of fatal and nonfatal cardiovascular events , and a composite of renal events was assessed using proportional hazards regression and adjusting for multiple potential confounders . RESULTS Greater SBV was associated with higher overall mortality . The adjusted hazard ratio ( 95 % confidence interval ) was 2.82 ( 1.14 - 6.95 ) comparing the highest with lowest tertile of SBV . A similar comparison revealed that greater SBV was also associated with cardiovascular mortality ( adjusted hazard ratio , 4.91 ; 1.12 - 21.50 ) . SBV was associated with both the cardiovascular renal composite endpoints in unadjusted but not adjusted analyses . CONCLUSIONS In African Americans with CKD , SBV is strongly and independently associated with overall and cardiovascular mortality Visit-to-visit blood pressure ( BP ) variability has received considerable attention recently . The objective of our study is to define a variability measure that is independent of change over time and determine the association between longitudinal summary measures of BP measurements and mortality risk . Data for the study came from a prospect i ve cohort of 2906 adults , aged ≥60 years , in an urban primary care system with ⩽15 years of follow-up . Date s of death for deceased participants were retrieved from the National Death Index . Systolic and diastolic BP measurements from outpatient clinic visits were extracted from the Regenstrief Medical Record System . For each patient , the intercept , regression slope , and root mean square error for visit-to-visit variability were derived using linear regression models and used as independent variables in Cox proportional hazards models for both all-cause mortality and mortality attributable to coronary heart disease or stroke . Rate of change was associated with mortality risk in a U-shaped relationship and that participants with little or no change in BP had the lowest mortality risk . BP variability was not an independent predictor of mortality risk . By separating change over time from visit-to-visit variability in studies with relatively long follow-up , we demonstrated in this elderly primary care patient population that BP changes over time , not variability , were associated with greater mortality risk . Future research is needed to confirm our findings in other population BACKGROUND Visit-to-visit blood pressure variability ( BPV ) is a simple surrogate marker for the development of atherosclerotic diseases , cardiovascular and all-cause mortality . Nevertheless , the relative prognostic value of BPV in comparison with other established vascular assessment s remain uncertain . METHODS We prospect ively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events ( MACEs ) . Baseline brachial endothelial function , carotid intima-media thickness ( IMT ) and plaque burden , ankle-brachial index and arterial stiffness were determined . Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits . RESULTS After a mean 81 ± 12 month 's follow-up , 123 patients ( 19 % ) developed MACEs . Patients who developed a MACE had significantly higher systolic BPV , more severe endothelial function , arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE ( all P<0.01 ) . BPV significantly correlated with all of the vascular assessment s ( P<0.01 ) . A high carotid IMT had the greatest prognostic value in predicting development of a MACE ( area under receiver operating characteristic curve ( AUC ) 0.69 ± 0.03 , P<0.01 ) . A high BPV also had moderate prognostic value in prediction of MACE ( AUC 0.65 ± 0.03 , P<0.01 ) . After adjustment of confounding factors , a high BPV remained a significant independent predictor of MACE ( hazards ratio 1.67 , 95 % confidence interval 1.14 - 2.43 , P<0.01 ) . CONCLUSIONS Compared with established surrogate markers of atherosclerosis , visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases Background : In certain patients in routine practice , blood pressure ( BP ) measurements differ substantially from week to week or month to month . Although often assumed to be r and om , such variability could provide information on underlying pathology or prognosis . In order to be informative , however , visit-to-visit BP variability would have to be neither r and om ( i.e. it should be reproducible over time within individuals ) nor artefactual ( i.e. it should not be an artefact of the method /timing of measurement , for example ) . Methods : We quantified visit-to-visit variability in BP and explored potential confounding factors by analysing repeat measurements obtained every few months during follow-up in two large trials in patients with a transient ischaemic attack ( TIA ) or minor ischaemic stroke : the UK-TIA Aspirin Trial ( effect of aspirin , effect of season and day of the week of measurement ) and the European Carotid Surgery Trial ( ECST – effect of carotid endarterectomy ) . By comparing different periods of follow-up , we also determined the reproducibilities of mean and several different measures of variability for both systolic ( SBP ) and diastolic BP ( DBP ) . Results : The mean absolute difference between adjacent SBP readings was 14.7 mm Hg in the UK-TIA Trial and 16.0 mm Hg in ECST . Visit-to-visit variability in both SBP and DBP were independent of the potentially confounding factors studied , but reproducibility of all the variability measures was statistically significantly greater than zero . Reproducibility ( intraclass correlation ) of st and ard deviation of SBP was 0.32 ( p < 0.0001 ) in the UK-TIA Trial and 0.18 ( p = 0.0007 ) in ECST . Consequently , classification of patients with high ( top quintile ) or low ( bottom quintile ) variability was consistent over time ( observed/expected = 2.21 , 95 % confidence interval 1.71–2.85 , p < 0.0001 , and 1.65 , 1.23–2.21 , p = 0.0007 , respectively ) . Reproducibility increased with the number of measurements used to calculate variability , and was independent of any correlation with mean BP . Conclusions : Visit-to-visit variability in BP in these population s was reproducible , independently of any correlation with mean BP , demonstrating that visit-to-visit intra-individual BP variability is not r and om BACKGROUND AND PURPOSE Both blood pressure ( BP ) and its variability ( BPV ) are established risk factors for development of atherosclerotic disease and are associated with an increased risk for cardiovascular and all-cause mortality . The prognostic implication s of outpatient clinic visit-to-visit BPV amongst patients with lacunar infa rct ion are nevertheless unknown . METHODS The clinical outcome of 281 patients with lacunar infa rct ion was prospect ively followed up . The average BP and BPV , as determined by the st and ard deviation of the systolic and diastolic BP , were recorded during a mean 13 ± 6 outpatient clinic visits . RESULTS The mean age of the population was 70 ± 10 years . After a mean 78 ± 18 months follow-up , 65 patients died ( 23 % ) , 31 % ( 20/65 ) due to cardiovascular causes ; 14 % and 7 % developed recurrent stroke and acute coronary syndrome . After adjusting for age , sex , mean systolic and diastolic BP , cardiovascular risk factors and comorbidities , patients with a systolic BPV of the third tertile had significantly higher risk of all-cause mortality [ hazard ratio ( HR ) 1.97 , 95 % confidence interval ( CI ) 1.02 - 3.80 , P = 0.04 ) and cardiovascular mortality ( HR 7.64 , 95 % CI 1.65 - 35.41 , P < 0.01 ) than those with systolic BPV of the first tertile . Nevertheless , systolic BPV did not predict recurrent stroke or acute coronary syndrome . Diastolic BPV did not predict various adverse clinical outcomes . CONCLUSIONS Visit-to-visit systolic BPV predicts long-term all-cause and cardiovascular mortality after lacunar infa rct , independent of conventional risk factors including average BP control |
12,409 | 29,988,997 | Conclusions There is a higher risk of relapse for those who undergo total or targeted discontinuation strategies compared with maintenance antipsychotics in FEP sample s. The effect size is moderate and the risk difference is lower in trials of targeted discontinuation strategies . | Background Underst and ing the relative risks of maintenance treatment versus discontinuation of antipsychotics following remission in first episode psychosis ( FEP ) is an important area of practice . | Out of 253 patients fulfilling criteria for a first episode of schizophrenic illness , 120 entered a r and omised placebo-controlled trial of maintenance neuroleptic medication on discharge ; they were followed to relapse or loss to follow-up , for two years or to the end of the study . Of those on active medication , 46 % relapsed , as did 62 % of those on placebo ; the most important determinant of relapse was duration of illness prior to starting neuroleptic medication . This finding might be because extended duration of symptoms before admission is more likely to be present in illnesses which in any case will have poor prognosis , or because susceptibility to relapse is reduced by early institution of treatment . The study provides no data on which a decision between these alternative explanations can be based Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more CONTEXT Progressive brain volume changes in schizophrenia are thought to be due principally to the disease . However , recent animal studies indicate that antipsychotics , the mainstay of treatment for schizophrenia patients , may also contribute to brain tissue volume decrement . Because antipsychotics are prescribed for long periods for schizophrenia patients and have increasingly widespread use in other psychiatric disorders , it is imperative to determine their long-term effects on the human brain . OBJECTIVE To evaluate relative contributions of 4 potential predictors ( illness duration , antipsychotic treatment , illness severity , and substance abuse ) of brain volume change . DESIGN Predictors of brain volume changes were assessed prospect ively based on multiple informants . SETTING Data from the Iowa Longitudinal Study . PATIENTS Two hundred eleven patients with schizophrenia who underwent repeated neuroimaging beginning soon after illness onset , yielding a total of 674 high-resolution magnetic resonance scans . On average , each patient had 3 scans ( ≥2 and as many as 5 ) over 7.2 years ( up to 14 years ) . MAIN OUTCOME MEASURE Brain volumes . RESULTS During longitudinal follow-up , antipsychotic treatment reflected national prescribing practice s in 1991 through 2009 . Longer follow-up correlated with smaller brain tissue volumes and larger cerebrospinal fluid volumes . Greater intensity of antipsychotic treatment was associated with indicators of generalized and specific brain tissue reduction after controlling for effects of the other 3 predictors . More antipsychotic treatment was associated with smaller gray matter volumes . Progressive decrement in white matter volume was most evident among patients who received more antipsychotic treatment . Illness severity had relatively modest correlations with tissue volume reduction , and alcohol/illicit drug misuse had no significant associations when effects of the other variables were adjusted . CONCLUSIONS Viewed together with data from animal studies , our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time , suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use OBJECTIVE To compare the consequences of a guided discontinuation strategy and maintenance treatment in remitted first-episode psychosis in terms of relapse rates and functional outcome . METHOD The study was conducted in 7 mental health care organizations and the Department of Psychiatry of the University Medical Center Groningen in The Netherl and s , covering a catchment area of 3.1 million inhabitants . A sample of 131 remitted first-episode patients , aged 18 to 45 years , with a DSM-IV diagnosis of schizophrenia or related psychotic disorder was included ( i.e. , all patients with a first psychotic episode from October 2001 through December 2002 who were willing to participate ) . After 6 months of positive symptom remission , they were r and omly and openly assigned to the discontinuation strategy or maintenance treatment . Maintenance treatment was carried out according to American Psychiatric Association guidelines , preferably using low-dose atypical antipsychotics . The discontinuation strategy was carried out by gradual symptom-guided tapering of dosage and discontinuation if feasible . Follow-up was 18 months . Main outcome measures were relapse rates and social and vocational functioning . RESULTS Twice as many relapses occurred with the discontinuation strategy ( 43 % vs. 21 % , p = .011 ) . Of patients who received the strategy , approximately 20 % were successfully discontinued . Recurrent symptoms caused another approximately 30 % to restart antipsychotic treatment , while in the remaining patients discontinuation was not feasible at all . There were no advantages of the discontinuation strategy regarding functional outcome . CONCLUSIONS Only a limited number of patients can be successfully discontinued . High relapse rates do not allow a discontinuation strategy to be universal practice . However , if relapse risk can be carefully managed by close monitoring , in some remitted first-episode patients a guided discontinuation strategy may offer a feasible alternative to maintenance treatment . Further research is needed to find predictors of successful discontinuation In a simple remitted , nonpsychotic schizophrenics , the relapse rate within one year was significantly higher for those patients taking placebo as opposed to those taking fluphenazine hydrochloride orally or fluphenazine decanoate . There were no differences in relapse rates between the two active drugs , but there were significantly more terminations due to toxicity from fluphenazine decanoate than from pluphenazine given orally , entirely due to the fact that in 35 % of patients receiving fluphenazine decanoate , severe akinesia developed IMPORTANCE Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis ( FEP ) showed higher relapse rates but no other disadvantages compared with maintenance treatment ; however , long-term effects on recovery have not been studied before . OBJECTIVE To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation ( DR ) vs maintenance treatment ( MT ) trial . DESIGN Seven-year follow-up of a 2-year open r and omized clinical trial comparing MT and DR . SETTING One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million- population catchment area . Of these , 111 patients refused to participate and 18 patients did not experience remission . PARTICIPANTS After 7 years , 103 patients ( 80.5 % ) of 128 patients who were included in the original trial were located and consented to follow-up assessment . INTERVENTION After 6 months of remission , patients were r and omly assigned to DR strategy or MT for 18 months . After the trial , treatment was at the discretion of the clinician . MAIN OUTCOMES AND MEASURES Primary outcome was rate of recovery , defined as meeting the criteria of symptomatic and functional remission . Determinants of recovery were examined using logistic regression analysis ; the treatment strategy ( MT or DR ) was controlled for baseline parameters . RESULTS The DR patients experienced twice the recovery rate of the MT patients ( 40.4 % vs 17.6 % ) . Logistic regression showed an odds ratio of 3.49 ( P = .01 ) . Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates . CONCLUSIONS AND RELEVANCE Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT . To our knowledge , this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP . Additional studies are necessary before these results are incorporated into general practice . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N16228411 Abstract Objective . To assess the effect of withdrawal of antipsychotic treatment on relapse risk in remitted first-episode schizophrenia patients . Methods . First-episode 1-year stable and remitted out patients with a schizophrenic disorder were r and omly allocated to continuation of their antipsychotic regimen for at least 6 months ( N = 9 ) , or gradual withdrawal ( N = 11 ) . Primary outcome was the difference in cumulative relapse-free survival at 9 months . Results . Recruitment was terminated prematurely on 26 October 2005 . The cumulative relapse-free survival was 88 % ( SE = 0.12 ) in the continuation and 18 % ( SE = 0.12 ) in the discontinuation group ( P = 0.001 ) at 9 months follow-up . Conclusions . Discontinuation of antipsychotic medication markedly increases the risk of relapse in stable remitted first-episode schizophrenia patients . In future studies the topics of safety monitoring and sampling of patients should receive extra attention OBJECTIVE To describe the longer-term clinical and functional outcome of a large , epidemiologic representative cohort of individuals experiencing a first episode of psychosis . METHOD A naturalistic , prospect i ve follow-up of an epidemiologic sample of 723 consecutive first-episode psychosis patients , followed between January 1998 and April 2005 , at a median of 7.4 years after initial presentation to the Early Psychosis Prevention and Intervention Centre ( EPPIC ) in Melbourne , Australia . EPPIC is a frontline public mental health early psychosis program , servicing a geographically defined catchment area with a population of about 800,000 people . The main outcome measures included the Brief Psychiatric Rating Scale , the Schedule for the Assessment of Negative Symptoms , the Beck Depression Inventory , the Global Assessment of Functioning Scale , the Social and Occupational Functioning Assessment Scale , the Quality of Life Scale , and the remission criteria developed by the Remission in Schizophrenia Working Group . RESULTS Follow-up information was collected on up to 90.0 % ( n = 651 ) of the baseline cohort of 723 participants , with 66.9 % ( n = 484 ) interviewed . In the last 2 years , 57 % of individuals with schizophrenia/schizophreniform , 54 % with schizoaffective disorder , 62 % with affective psychosis , and 68 % with other psychotic disorders reported some paid employment . Depending upon the criteria applied , symptomatic remission at follow-up was observed in 37%-59 % of the cohort . Social/vocational recovery was observed in 31 % of the cohort . Approximately a quarter achieved both symptomatic remission and social/vocational recovery . CONCLUSION The relatively positive outcomes are consistent with a beneficial effect of specialized early intervention programs ; however it is premature to draw firm conclusions . There was no control group and there are many differences between the relevant comparison studies and the present one . Although difficult to conduct , large scale controlled health services research trials are required to definitively determine the impact and optimal duration of specialized early psychosis programs OBJECTIVE The goal of this report was to examine the clinical course following neuroleptic discontinuation of patients with recent-onset schizophrenia who had been receiving maintenance antipsychotic treatment for at least 1 year . METHOD Fifty-three volunteer patients with recent-onset schizophrenia who had been clinical ly stabilized on a maintenance regimen of fluphenazine decanoate for a mean of 16.7 months had their antipsychotic medications withdrawn under clinical supervision . Participants initially entered a 24-week , double-blind crossover trial in which fluphenazine and placebo were administered for 12 weeks each . For those who did not experience symptom exacerbation or relapse during this period , fluphenazine was openly withdrawn ; participants were then followed for up to 18 additional months . RESULTS When a low threshold for defining symptom reemergence was used , 78 % ( N=39 of 50 ) of the patients experienced an exacerbation or relapse within 1 year ; 96 % ( N=48 of 50 ) did so within 2 years . Mean time to exacerbation or relapse was 235 days . When hospitalization was used as a relapse criterion , only six of 45 of individuals ( 13 % ) experiencing an exacerbation or relapse who continued in treatment in the clinic were hospitalized , demonstrating the sensitivity of the psychotic exacerbation criterion . CONCLUSIONS The vast majority of clinical ly stable individuals with recent-onset schizophrenia will experience an exacerbation or relapse after antipsychotic discontinuation , even after more than a year of maintenance medication . However , clinical monitoring and a low threshold for reinstating medications can prevent hospitalization for the majority of these patients AIMS Discontinuation of antipsychotics following remission in first episode psychosis ( FEP ) is a contentious area of practice . We aim ed to investigate the views of early psychosis clinicians on this important clinical question . METHODS We design ed an 11 question online survey on medication discontinuation following remission of symptoms in FEP . The question naire was distributed to early intervention team workers in Engl and and Wales via members of the National Early Psychosis Network who were requested to distribute it to their teams . RESULTS We received 172 question naire responses ; 37 % were nurses , 33 % doctors , 11 % psychologists and 19 % were other allied health professionals . The average years of experience in psychiatry was 16.9 . 75.4 % of respondents thought that greater than 60 % of patients would like to be considered for guided medication reduction/discontinuation . Only 31.4 % of respondents said that medication should be continued for over a year following remission . 61.4 % of respondents felt that the quality of life of individuals was better in those who stop medication following remission . There was a significant difference in the response of professional groups to this question . 82.6 % of respondents said they would be happy to support their patients in participating in a r and omized trial of grade d antipsychotic reduction/discontinuation versus maintenance medication . CONCLUSIONS The views of clinicians regarding prophylactic antipsychotic medication following remission in FEP are much less conservative than those in current guidelines ; concern was expressed by many about the impact of antipsychotic medication on quality of life . A r and omized trial of maintenance antipsychotic medication versus grade d reduction/discontinuation is feasible and has considerable clinician support Twenty-eight patients who had recently recovered from an acute-onset , first-episode schizophrenic illness were r and omly given fluphenazine hydrochloride or decanoate or placebo for a one-year period in a double-blind study . Seven of 17 patients ( 14 % ) receiving placebo experienced a psychotic relapse , whereas none of 11 drug-treated patients experienced a relapse . Eighteen ( 69 % ) of the 26 patients available for follow-up ( mean interval , 3.5 years ) experienced a second psychotic relapse either during the study or afterward , and 50 % ( 14/28 ) of the original sample experienced a third episode OBJECTIVE After acute treatment of the first illness episode in schizophrenia , antipsychotic maintenance treatment is recommended for at least 1 year . Evidence for the optimal subsequent treatment is still scarce . Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients ; however , a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients . The current study was therefore design ed to compare prospect ively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia . METHOD A r and omized controlled trial was conducted within the German Research Network on Schizophrenia . Entry screening took place between November 2000 and May 2004 . After 1 year of antipsychotic maintenance treatment , stable first-episode patients were r and omly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment . In case of prodromal symptoms of an impending relapse , patients in both groups received early drug intervention , guided by a decision algorithm . The primary outcome measure was relapse ( increase in the Positive and Negative Syndrome Scale positive score > 10 , Clinical Global Impressions-Change score ≥ 6 , and decrease in Global Assessment of Functioning score > 20 between 2 visits ) . RESULTS Of 96 first-episode patients , only 44 were eligible for the assigned treatment ( maintenance treatment , n = 23 ; intermittent treatment , n = 21 ) . The rates of relapse ( 19 % vs 0 % ; P = .04 ) and deterioration ( up to 57 % vs 4 % ; P < .001 ) were significantly higher in the intermittent treatment group than in the maintenance treatment group , but quality -of-life scores were comparable . Intermittent treatment patients received a significantly lower amount of antipsychotics ( in haloperidol equivalents ; P < .001 ) and tended to show fewer side effects , particularly extrapyramidal side effects . CONCLUSIONS Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse , even in stable first-episode patients after 1 year of maintenance treatment , and should be the preferred treatment option . However , about 50 % of patients remain stable at a significantly lower drug dose and show fewer side effects , and a substantial proportion refuse maintenance treatment . Alternative long-term treatment strategies , including targeted intermittent treatment , should therefore be provided in individual cases . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00159120 Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment . Design 12 month r and omised , double blind , placebo controlled trial . Setting Early psychosis outpatient clinics in Hong Kong . Participants 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis . Interventions Patients received either maintenance treatment with quetiapine ( 400 mg/day ) or placebo and were followed up for the next 12 months or until a relapse occurred . Main outcome measure Relapse assessed monthly and defined as re-emergence of psychotic symptoms ( delusions , conceptual disorganisation , hallucinations , suspiciousness , and unusual thought content ) according to predefined thresholds . Results 178 patients were r and omised ( 89 to quetiapine and 89 to placebo ) . The Kaplan-Meier estimate of the risk of relapse at 12 months was 41 % ( 95 % confidence interval 29 % to 53 % ) for the quetiapine group and 79 % ( 68 % to 90 % ) for the placebo group ( P<0.001 ) . Although quetiapine was generally well tolerated , the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group ( 18 % ; 16/89 ) than in the placebo group ( 8 % ; 7/89 ) ( relative risk 2.29 , 95 % confidence interval 0.99 to 5.28 ; χ2=3.20 , df=1 ; P=0.07 ) . Conclusion In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment , maintenance treatment with quetiapine compared with placebo result ed in a substantially lower rate of relapse during the following year . Trial registration Clinical trials NCT00334035 ABSTRACT — Of 49 schizophrenic patients followed up 2 years after their first admission to hospital , 37 % were well , 47 % had been readmitted to hospital at some time over the 2 years , and 18mo showed schizophrenic symptoms at follow‐up . A poor outcome at 2 years was associated with male sex , poor outcome after the first 5 weeks of the first admission , negative schizophrenic symptoms on first admission , and a diagnosis of definite or probable schizophrenia using the Feighner criteria . Only 23 % were in employment . A small double‐blind discontinuation study of maintenance antipsychotic medication during the second year found more relapses in those switched to placebo medication . Repeat psychometric assessment at 2 years confirmed modest improvements found at 12 months ; that is , there was no evidence of intellectual decline . Relatives showed no more psychosocial distress than that found in a normal community sample ; what distress there was correlated with patients ’ schizophrenic symptoms |
12,410 | 30,320,443 | Compared to ADT alone , the early ( within 120 days of beginning ADT ) addition of taxane-based chemotherapy to ADT for hormone-sensitive prostate cancer probably prolongs both overall and disease-specific survival and delays disease progression .
There may be an increase in toxicity with taxane-based chemotherapy in combination with ADT . | BACKGROUND There has been considerable development in the treatment of advanced prostate cancer over the last decade .
A number of agents , including docetaxel , cabazitaxel , abiraterone acetate , enzalutamide and sipuleucel-T , have been reported to improve outcomes in men with castration-resistant disease and their use is being explored in hormone-sensitive prostate cancer .
OBJECTIVES To assess the effects of early taxane-based chemohormonal therapy for newly diagnosed , metastatic , hormone-sensitive prostate cancer . | BACKGROUND Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P<0.001 for both comparisons with mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone A multicenter phase I clinical trial of RP 56976 ( docetaxel ) , a new anticancer drug , was performed with single and repeated doses . Based on the results of phase I clinical trials conducted in the United States and Europe , the starting dose was 10 mg/m2 . The dose was subsequently increased to 20 , 50 , 70 and 90 mg/m2 . A dose of 60 mg/m2 was additionally tested . Single administrations of the six dose levels were performed in a total of 27 patients via intravenous drip infusion over one hour . Ten of the patients subsequently received repeated doses at three of the dose levels in the same manner . The dose limiting factor ( DLF ) of docetaxel is leukopenia ( especially , neutropenia ) . Based on the observation of the DLF , the maximum tolerated dose ( MTD ) was determined to be 70 - 90 mg/m2 . The white blood cell count reached a nadir about 9.5 - 19.5 days ( median ) after administration , and took 7 - 11 days ( median ) to recover . Other adverse reactions observed were nausea/vomiting anorexia , alopecia , diarrhea , fatigue and fever , which were all acceptable . The results of this trial suggest that a dosage regimen of 60 mg/m2 at 3- to 4 week intervals is appropriate in an early phase II clinical trial BACKGROUND Docetaxel administered every 3 weeks is a st and ard treatment for castration-resistant advanced prostate cancer . We hypothesised that 2-weekly administration of docetaxel would be better tolerated than 3-weekly docetaxel in patients with castration-resistant advanced prostate cancer , and did a prospect i ve , multicentre , r and omised , phase 3 study to compare efficacy and safety . METHODS Eligible patients had advanced prostate cancer ( metastasis , a prostate-specific-antigen test result of more than 10·0 ng/mL , and WHO performance status score of 0 - 2 ) , had received no chemotherapy ( except with estramustine ) , had undergone surgical or chemical castration , and had been referred to a treatment centre in Finl and , Irel and , or Sweden . Enrolment and treatment were done between March 1 , 2004 , and May 31 , 2009 . R and omisation was done central ly and stratified by centre and WHO performance status score of 0 - 1 vs 2 . Patients were assigned 75 mg/m(2 ) docetaxel intravenously on day 1 of a 3-week cycle , or 50 mg/m(2 ) docetaxel intravenously on days 1 and 15 of a 4-week cycle . 10 mg oral prednisolone was administered daily to all patients . The primary endpoint was time to treatment failure ( TTTF ) . We assessed data in the per- protocol population . This study is registered with Clinical Trials.gov , number NCT00255606 . FINDINGS 177 patients were r and omly assigned to the 2-weekly docetaxel group and 184 to the 3-weekly group . 170 patients in the 2-weekly group and 176 in the 3-weekly group were included in the analysis . The 2-weekly administration was associated with significantly longer TTTF than was 3-weekly administration ( 5·6 months , 95 % CI 5·0 - 6·2 vs 4·9 months , 4·5 - 5·4 ; hazard ratio 1·3 , 95 % CI 1·1 - 1·6 , p=0·014 ) . Grade 3 - 4 adverse events occurred more frequently in the 3-weekly than in the 2-weekly administration group , including neutropenia ( 93 [ 53 % ] vs 61 [ 36 % ] ) , leucopenia ( 51 [ 29 % ] vs 22 [ 13 % ] ) , and febrile neutropenia ( 25 [ 14 % ] vs six [ 4 % ] ) . Neutropenic infections were reported more frequently in patients who received docetaxel every 3 weeks ( 43 [ 24 % ] vs 11 [ 6 % ] , p=0·002 ) . INTERPRETATION Administration of docetaxel every 2 weeks seems to be well tolerated in patients with castration-resistant advanced prostate cancer and could be a useful option when 3-weekly single-dose administration is unlikely to be tolerated . FUNDING Sanofi Background Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer . We assessed the effect of this combination in men starting long‐term and rogen‐deprivation therapy ( ADT ) , using a multigroup , multistage trial design . Methods We r and omly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate ( 1000 mg daily ) and prednisolone ( 5 mg daily ) ( combination therapy ) . Local radiotherapy was m and ated for patients with node‐negative , nonmetastatic disease and encouraged for those with positive nodes . For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease , treatment continued until radiologic , clinical , or prostate‐specific antigen ( PSA ) progression ; otherwise , treatment was to continue for 2 years or until any type of progression , whichever came first . The primary outcome measure was overall survival . The intermediate primary outcome was failure‐free survival ( treatment failure was defined as radiologic , clinical , or PSA progression or death from prostate cancer ) . Results A total of 1917 patients underwent r and omization from November 2011 through January 2014 . The median age was 67 years , and the median PSA level was 53 ng per milliliter . A total of 52 % of the patients had metastatic disease , 20 % had node‐positive or node‐indeterminate nonmetastatic disease , and 28 % had node‐negative , nonmetastatic disease ; 95 % had newly diagnosed disease . The median follow‐up was 40 months . There were 184 deaths in the combination group as compared with 262 in the ADT‐alone group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.52 to 0.76 ; P<0.001 ) ; the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease . There were 248 treatment‐failure events in the combination group as compared with 535 in the ADT‐alone group ( hazard ratio , 0.29 ; 95 % CI , 0.25 to 0.34 ; P<0.001 ) ; the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease . Grade 3 to 5 adverse events occurred in 47 % of the patients in the combination group ( with nine grade 5 events ) and in 33 % of the patients in the ADT‐alone group ( with three grade 5 events ) . Conclusions Among men with locally advanced or metastatic prostate cancer , ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure‐free survival than ADT alone . ( Funded by Cancer Research U.K. and others ; STAMPEDE Clinical Trials.gov number , NCT00268476 , and Current Controlled Trials number , IS RCT N78818544 . Recent insights into the regulation of the and rogen receptor ( AR ) activity led to novel therapeutic targeting of AR function in prostate cancer patients . Docetaxel is an approved chemotherapy for treatment of castration-resistant prostate cancer ; however , the mechanism underlying the action of this tubulin-targeting drug is not fully understood . This study investigates the contribution of microtubules and the cytoskeleton to and rogen-mediated signaling and the consequences of their inhibition on AR activity in human prostate cancer . Tissue microarrays from docetaxel-treated and untreated prostate cancer patients were comparatively analyzed for prostate-specific antigen ( PSA ) and AR immunoreactivity . The AR transcriptional activity was determined in prostate cancer cells in vitro , based on PSA mRNA expression and the and rogen response element reporter activity . The interaction of AR with tubulin was examined by immunoprecipitation and immunofluorescence . Treatment of prostate cancer patients with docetaxel led to a significant translocation of AR . In untreated specimens , 50 % prostate tumor cells exhibited nuclear accumulation of AR , compared with docetaxel-treated tumors that had significantly depleted nuclear AR ( 38 % ) , paralleled by an increase in cytosolic AR . AR nuclear localization correlated with PSA expression . In vitro , exposure of prostate cancer cells to paclitaxel ( 1 μmol/L ) or nocodazole ( 5 μg/mL ) inhibited and rogen-dependent AR nuclear translocation by targeting AR association with tubulin . Introduction of a truncated AR indicated the requirement of the NH(2)-terminal domain for AR-tubulin interaction . Our findings show that in addition to blocking cell division , docetaxel impairs AR signaling , evidence that enables new insights into the therapeutic efficacy of microtubule-targeting drugs in prostate cancer |
12,411 | 30,424,761 | Conclusion Peer-education-based interventions appear to be particularly effective in facilitating the uptake of HIV-related knowledge , particularly pertaining to transmission routes . | Background As high stigmatization of HIV and relatively low knowledge of HIV transmission and prevention measures persist in Sub-Saharan Africa , the improvement of HIV-related knowledge , and the evaluation of which types of interventions are most effective in this regard , is an important aspect of further prevention efforts .
In addition , it is of interest to assess whether improvements in HIV-related knowledge may actually lead to increased engagement in preventive behaviours and ultimately lower HIV transmission .
This study therefore aims to systematic ally review and meta-analyse the evidence for the effect of HIV-related knowledge interventions on 1 ) the improvement of HIV-related knowledge , 2 ) subsequent risk reduction behaviour ( condom use ) , 3 ) lower incidence of HIV infection . | Objective : To assess effects of a combined microfinance and training intervention on HIV risk behavior among young female participants in rural South Africa . Design : Secondary analysis of quantitative and qualitative data from a cluster r and omized trial , the Intervention with Microfinance for AIDS and Gender Equity study . Methods : Eight villages were pair-matched and r and omly allocated to receive the intervention . At baseline and after 2 years , HIV risk behavior was assessed among female participants aged 14–35 years . Their responses were compared with women of the same age and poverty group from control villages . Intervention effects were calculated using adjusted risk ratios employing village level summaries . Qualitative data collected during the study explored participants ' responses to the intervention including HIV risk behavior . Results : After 2 years of follow-up , when compared with controls , young participants had higher levels of HIV-related communication ( adjusted risk ratio 1.46 , 95 % confidence interval 1.01–2.12 ) , were more likely to have accessed voluntary counseling and testing ( adjusted risk ratio 1.64 , 95 % confidence interval 1.06–2.56 ) , and less likely to have had unprotected sex at last intercourse with a nonspousal partner ( adjusted risk ratio 0.76 , 95 % confidence interval 0.60–0.96 ) . Qualitative data suggest a greater acceptance of intrahousehold communication about HIV and sexuality . Although women noted challenges associated with acceptance of condoms by men , increased confidence and skills associated with participation in the intervention supported their introduction in sexual relationships . Conclusions : In addition to impacts on economic well being , women 's empowerment and intimate partner violence , interventions addressing the economic and social vulnerability of women may contribute to reductions in HIV risk behavior Adolescents and young adults in sub-Saharan Africa ( SSA ) are particularly vulnerable to human immunodeficiency virus ( HIV ) and acquired immune deficiency syndrome ( AIDS ) infection . Adolescents orphaned as a direct result of HIV/AIDS are at an elevated risk of acquiring HIV/AIDS and other sexually transmitted infections . However , limited empirical evidence exists on HIV knowledge and prevention programs , especially those design ed to address HIV information gaps among adolescents . This study evaluates the effect of a peer mentorship program provided in addition to other supportive services on HIV/AIDS knowledge , beliefs , and prevention attitudes , among school-going orphaned adolescents in southern Ug and a. We utilize data from the Bridges to the Future Study , a 5-year longitudinal r and omized experimental study funded by the National Institute of Child Health and Human Development . Out of the 1410 adolescents enrolled in the study ( average age = 12.7 at study initiation ) , 855 of them participated in a nine-session , curriculum based peer mentorship program . We analyzed data collected at baseline and 12-months post intervention initiation . The results from bivariate and regression analysis indicate that , controlling for socioeconomic characteristics , adolescents who participated in a peer mentorship program were more likely than non- participants to report increased scores on HIV/AIDS knowledge ; better scores on desired HIV/AIDS-related beliefs ; and better scores on HIV/AIDS prevention attitudes . Overall , the study findings point to the potential role of a peer mentorship program in promoting the much-desired HIV/AIDS knowledge , beliefs , and prevention attitudes among orphaned adolescents . Future programs and policies that support AIDS-orphaned adolescents in sub-Saharan Africa should consider incorporating peer mentoring programs that provide correct , age , and culturally appropriate HIV information to help protect orphaned adolescents and reduce the risk of HIV infections OBJECTIVES The purpose of this study was to test the effects of an education program in Tanzania design ed to reduce children 's risk of human immunodeficiency virus ( HIV ) infection and to improve their tolerance of and care for people with acquired immunodeficiency syndrome ( AIDS ) . METHODS A r and omized controlled community trial including baseline and 12-month follow-up surveys was employed . Public primary schools in the Arusha and Kilimanjaro regions of Tanzania were stratified according to location and r and omly assigned to intervention ( n = 6 ) or comparison ( n = 12 ) conditions . Of the 1063 sixth- grade students ( average age : 13.6 years ) who participated at baseline , 814 participated in the follow-up survey . RESULTS At follow-up , statistically significant effects favoring the intervention group were observed for exposure to AIDS information and communication , AIDS knowledge , attitudes toward people with AIDS , and subjective norms and behavioral intentions toward having sexual intercourse . A consistent positive but nonsignificant trend was seen for attitudes toward having sexual intercourse and for initiation of sexual intercourse during the previous year ( 7 % vs 17 % ) . CONCLUSIONS It is feasible and effective to train local teachers and health workers to provide HIV/AIDS education to Tanzanian primary school children BACKGROUND Intimate partner violence ( IPV ) is associated with HIV infection . We aim ed to assess whether provision of a combination of IPV prevention and HIV services would reduce IPV and HIV incidence in individuals enrolled in the Rakai Community Cohort Study ( RCCS ) , Rakai , Ug and a. METHODS We used pre-existing clusters of communities r and omised as part of a previous family planning trial in this cohort . Four intervention group clusters from the previous trial were provided st and ard of care HIV services plus a community-level mobilisation intervention to change attitudes , social norms , and behaviours related to IPV , and a screening and brief intervention to promote safe HIV disclosure and risk reduction in women seeking HIV counselling and testing services ( the Safe Homes and Respect for Everyone [ SHARE ] Project ) . Seven control group clusters ( including two intervention groups from the original trial ) received only st and ard of care HIV services . Investigators for the RCCS did a baseline survey between February , 2005 , and June , 2006 , and two follow-up surveys between August , 2006 , and April , 2008 , and June , 2008 , and December , 2009 . Our primary endpoints were self-reported experience and perpetration of past year IPV ( emotional , physical , and sexual ) and laboratory-based diagnosis of HIV incidence in the study population . We used Poisson multivariable regression to estimate adjusted prevalence risk ratios ( aPRR ) of IPV , and adjusted incidence rate ratios ( aIRR ) of HIV acquisition . This study was registered with Clinical Trials.gov , number NCT02050763 . FINDINGS Between Feb 15 , 2005 , and June 30 , 2006 , we enrolled 11 448 individuals aged 15 - 49 years . 5337 individuals ( in four intervention clusters ) were allocated into the SHARE plus HIV services group and 6111 individuals ( in seven control clusters ) were allocated into the HIV services only group . Compared with control groups , individuals in the SHARE intervention groups had fewer self-reports of past-year physical IPV ( 346 [ 16 % ] of 2127 responders in control groups vs 217 [ 12 % ] of 1812 responders in intervention groups ; aPRR 0·79 , 95 % CI 0·67 - 0·92 ) and sexual IPV ( 261 [ 13 % ] of 2038 vs 167 [ 10 % ] of 1737 ; 0·80 , 0·67 - 0·97 ) . Incidence of emotional IPV did not differ ( 409 [ 20 % ] of 2039 vs 311 [ 18 % ] of 1737 ; 0·91 , 0·79 - 1·04 ) . SHARE had no effect on male-reported IPV perpetration . At follow-up 2 ( after about 35 months ) the intervention was associated with a reduction in HIV incidence ( 1·15 cases per 100 person-years in control vs 0·87 cases per 100 person-years in intervention group ; aIRR 0·67 , 95 % CI 0·46 - 0·97 , p=0·0362 ) . INTERPRETATION SHARE could reduce some forms of IPV towards women and overall HIV incidence , possibly through a reduction in forced sex and increased disclosure of HIV results . Findings from this study should inform future work toward HIV prevention , treatment , and care , and SHARE 's ecological approach could be adopted , at least partly , as a st and ard of care for other HIV programmes in sub-Saharan Africa . FUNDING Bill & Melinda Gates Foundation , US National Institutes of Health , WHO , President 's Emergency Plan for AIDS Relief , Fogarty International Center Background While the HIV epidemic is levelling off in sub-Saharan Africa , it remains at an unacceptably high level . Young people aged 15 - 24 years remain particularly vulnerable , result ing in a regional HIV prevalence of 1.4 % in young men and 3.3 % in young women . This study assesses the effectiveness of a peer-led HIV prevention intervention in secondary schools in Rw and a on young people ’s sexual behavior , HIV knowledge and attitudes . Methods In a non-r and omized longitudinal controlled trial , fourteen schools were selected in two neighboring districts in Rw and a Bugesera ( intervention ) and Rwamagana ( control ) . Students ( n = 1950 ) in eight intervention and six control schools participated in three surveys ( baseline , six and twelve months in the intervention ) . Analysis was done using linear and logistic regression using generalized estimation equations adjusted for propensity score . Results The overall retention rate was 72 % . Time trends in sexual risk behavior ( being sexually active , sex in last six months , condom use at last sex ) were not significantly different in students from intervention and control schools , nor was the intervention associated with increased knowledge , perceived severity or perceived susceptibility . It did significantly reduce reported stigma . Conclusions Analyzing this and other interventions , we identified several reasons for the observed limited effectiveness of peer education : 1 ) intervention activities ( spreading information ) are not tuned to objectives ( changing behavior ) ; 2 ) young people prefer receiving HIV information from other sources than peers ; 3 ) outcome indicators are not adequate and the context of the relationship in which sex occurs and the context in which sex occurs is ignored . Effectiveness of peer education may increase through integration in holistic interventions and redefining peer educators ’ role as focal points for sensitization and referral to experts and services . Finally , we argue that a narrow focus on sexual risks will never significantly turn the tide Objective To assess the impact of Stepping Stones , a HIV prevention programme , on incidence of HIV and herpes simplex type 2 ( HSV-2 ) and sexual behaviour . Design Cluster r and omised controlled trial . Setting 70 villages ( clusters ) in the Eastern Cape province of South Africa . Participants 1360 men and 1416 women aged 15 - 26 years , who were mostly attending schools . Intervention Stepping Stones , a 50 hour programme , aims to improve sexual health by using participatory learning approaches to build knowledge , risk awareness , and communication skills and to stimulate critical reflection . Villages were r and omised to receive either this or a three hour intervention on HIV and safer sex . Interviewers administered question naires at baseline and 12 and 24 months and blood was tested for HIV and HSV-2 . Main outcome measures Primary outcome measure : incidence of HIV . Other outcomes : incidence of HSV-2 , unwanted pregnancy , reported sexual practice s , depression , and substance misuse . Results There was no evidence that Stepping Stones lowered the incidence of HIV ( adjusted incidence rate ratio 0.95 , 95 % confidence interval 0.67 to 1.35 ) . The programme was associated with a reduction of about 33 % in the incidence of HSV-2 ( 0.67 , 0.46 to 0.97 ; P=0.036)—that is , Stepping Stones reduced the number of new HSV-2 infections over a two year period by 34.9 ( 1.6 to 68.2 ) per 1000 people exposed . Stepping Stones significantly improved a number of reported risk behaviours in men , with a lower proportion of men reporting perpetration of intimate partner violence across two years of follow-up and less transactional sex and problem drinking at 12 months . In women desired behaviour changes were not reported and those in the Stepping Stones programme reported more transactional sex at 12 months . Conclusion Stepping Stones did not reduce incidence of HIV but had an impact on several risk factors for HIV — notably , HSV-2 and perpetration of intimate partner violence . Trial Registration Clinical Trials NCT00332878 Background HIV-1 control in sub-Saharan Africa requires cost-effective and sustainable programmes that promote behaviour change and reduce cofactor sexually transmitted infections ( STIs ) at the population and individual levels . Methods and Findings We measured the feasibility of community-based peer education , free condom distribution , income-generating projects , and clinic-based STI treatment and counselling services and evaluated their impact on the incidence of HIV-1 measured over a 3-y period in a cluster-r and omised controlled trial in eastern Zimbabwe . Analysis of primary outcomes was on an intention-to-treat basis . The income-generating projects proved impossible to implement in the prevailing economic climate . Despite greater programme activity and knowledge in the intervention communities , the incidence rate ratio of HIV-1 was 1.27 ( 95 % confidence interval [ CI ] 0.92–1.75 ) compared to the control communities . No evidence was found for reduced incidence of self-reported STI symptoms or high-risk sexual behaviour in the intervention communities . Males who attended programme meetings had lower HIV-1 incidence ( incidence rate ratio 0.48 , 95 % CI 0.24–0.98 ) , and fewer men who attended programme meetings reported unprotected sex with casual partners ( odds ratio 0.45 , 95 % CI 0.28–0.75 ) . More male STI patients in the intervention communities reported cessation of symptoms ( odds ratio 2.49 , 95 % CI 1.21–5.12 ) . Conclusions Integrated peer education , condom distribution , and syndromic STI management did not reduce population -level HIV-1 incidence in a declining epidemic , despite reducing HIV-1 incidence in the immediate male target group . Our results highlight the need to assess the community-level impact of interventions that are effective amongst targeted population sub-groups OBJECTIVE Little research has tested HIV/sexually transmitted infection ( STI ) risk-reduction interventions ' effects on early adolescents as they age into middle and late adolescence . This study tested whether intervention-induced reductions in unprotected intercourse during a 12-month period endured over a 54-month period and whether the intervention reduced the prevalence of STIs , which increase risk for HIV . METHOD Grade 6 learners ( mean age = 12.4 years ) participated in a 12-month trial in Eastern Cape Province , South Africa , in which 9 matched pairs of schools were r and omly selected and within pairs r and omized to a theory-based HIV/STI risk-reduction intervention or an attention-control intervention . They completed 42- and 54-month postintervention measures of unprotected intercourse ( the primary outcome ) , other sexual behaviors , theoretical constructs , and , at 42- and 54-month follow-up only , biologically confirmed curable STIs ( chlamydial infection , gonorrhea , and trichomoniasis ) and herpes simplex virus 2 . RESULTS The HIV/STI risk-reduction intervention reduced unprotected intercourse averaged over the entire follow-up period ( OR = 0.42 , 95 % CI [ 0.22 , 0.84 ] ) , an effect not significantly reduced at 42- and 54-month follow-up compared with 3- , 6- , and 12-month follow-ups . The intervention caused positive changes on theoretical constructs averaged over the 5 follow-ups , although most effects weakened at long-term follow-up . Although the intervention 's main effect on STIs was nonsignificant , an Intervention Condition × Time interaction revealed that it significantly reduced curable STIs at 42-month follow-up in adolescents who reported sexual experience . CONCLUSION These results suggest that theory-based behavioral interventions with early adolescents can have long-lived effects in the context of a generalized severe HIV epidemic OBJECTIVES This study represents a comprehensive assessment of differences between participants in an HIV/AIDS prevention program ( SHAPE : Sustainability , Hope , Action , Prevention , Education ) and non- participants in knowledge , attitudes and practice s with a focus on cultural , sociological and economic variables . METHODS We developed an eight-page question naire that was administered to 933 r and omly selected students at the University of Zimbabwe . Survey items addressed sexual decision-making , condom use , limiting sexual partners , cultural power dynamics and access to HIV testing . RESULTS Results show participants are statistically more likely to report being sexually abstinent , and underst and the prevention benefits of condom use . SHAPE members had fewer sexual partners in the previous year than non-SHAPE members ( 1.4 vs. 2.2 ) . SHAPE members were significantly more likely ( 67 % ) than non-SHAPE respondents ( 48 % ) to indicate that they knew their HIV sero-status and to state that they knew their status because they had been tested ( 85 % vs. 71 % ) . DISCUSSION Though we found differences between the groups suggesting that program participation increases awareness concerning gender equity , there continue to be many intractable cultural attitudes in this age group . Findings suggest that the attitudes and practice s of young men and women are changing , but that progress in some areas does not assure progress in all areas In sub-Saharan Africa , 60 % of people living with HIV are women and most are of childbearing age . Alarmingly , seroconversion rates during pregnancy are high and increase as pregnancy progresses , highlighting the importance of increasing HIV-knowledge among pregnant women and their partners . This study compared sexual risk behavior , HIV knowledge and condom use pre- to post-partum among South African couples ( n = 239 couples ) r and omly assigned to an intervention or an enhanced st and ard of care with the PMTCT protocol at rural community health antenatal clinics . Consistent condom use and HIV-related knowledge increased baseline to post-intervention and was maintained at long term follow up post-partum among participants in the intervention condition . HIV knowledge mediated the relationship between the intervention and consistent condom use . Results from this pilot study provide support for the integration of HIV risk reduction interventions for both women and men into existing PMTCT services during and following pregnancy . ResumenEn el África subsahariana , 60 % de las personas viviendo con VIH son mujeres y la mayoría son de edad que pueden tener hijos . Alarmantemente , las tasas de seroconversión del VIH durante el embarazo son altas y aumentan mientras el embarazo progresa , enfatiz and o la importancia del conocimiento del VIH entre las mujeres embarazadas y sus compañeros . Este estudio comparó la conducta del riesgo sexual , conocimiento acerca del VIH , y el uso de condones antes y después del parto entre las parejas del Sur de Africa ( n = 239 parejas ) asignadas al azar a una intervención o a mayor nivel de atención con el protocol PMTCT en clínicas prenatales de la salud de la comunidad rural . El uso consistente del condón y el conocimiento acerca del VIH aumentó de línea de base para después de la intervención y fue mantenida por largo tiempo en el cuidado postparto entre los participantes del grupo de intervención . El conocimiento acerca del VIH medió la relación entre la intervención y el uso consistente del condón . Result ados de este estudio piloto proveé ayuda para la integración entre la intervención de reducir el riesgo para mujeres y hombres en los servicios PMTCT durante y subsecuente al embarazo This paper discusses the application of an information , motivation and behavioural skills ( IMB ) model in a school-based programme for the reduction of HIV risk behaviour among 259 Grade 11 learners in two high schools in Alex and ra township , Johannesburg . School 1 was the Experimental group , while School 2 was the Control group . After a baseline study ( Time 1 ) at both schools , a 3-week intervention programme was conducted at School 1 . A post-test ( Time 2 ) was conducted at both schools . The intervention was repeated at School 2 , followed by another post-test ( Time 3 ) at both schools . A final test ( Time 4 ) was conducted at both schools . While there were positive changes in the levels of HIV&AIDS IMB in learner participants , these changes may not be entirely attributed to the intervention . If an IMB model-based intervention is to be maximally effective in reducing HIV-risk behaviour among adolescents , it must focus on the behavioural , structural and socio-cultural context s in which adolescents live We developed and evaluated a military-focused HIV prevention intervention to enhance HIV risk-reduction knowledge , motivation , and behaviors among Angolan soldiers . Twelve bases were r and omly assigned to HIV prevention or control conditions , yielding 568 participants . HIV prevention participants received training in preventing HIV ( 4.5 days ) and malaria ( 0.5 days ) . Control participants received the reverse . Monthly booster sessions were available after each intervention . We assessed participants at baseline , 3 and 6 months after the training . HIV prevention participants reported greater condom use and less unprotected anal sex at 3 months , as well as greater HIV-related knowledge and perceived vulnerability at 3 and 6 months . Within-group analyses showed HIV prevention participants increased condom use , reduced unprotected vaginal sex , and reduced numbers of partners at both follow-ups , while control participants improved on some outcomes at 3 months only . A military-focused HIV prevention intervention may increase HIV-related knowledge , motivation , and risk reduction among African soldiers This demonstration project used student nurses ( n = 12 ) on community deployment to provide health instruction among rural school-age population s in Zimbabwe . A quasi-experimental ( pre- and post-test ) , non-equivalent control group design was used and consisted of 141 school pupils in the intervention group and 144 pupils in the comparison group ( N = 285 ) . The curriculum focused on prevention of STDs , HIV/AIDS and drugs ( alcohol , tobacco and marijuana ) . A gain in health knowledge scores among the intervention group was reported at post-test . More than 70 % of the pupils who received health instruction from student nurses gave a high approval rating of student nurses ' performance . Further , student nurses , teachers and tutors all support school health instruction by student nurses although tutors and teachers differ on teaching about condoms This study used a quasi-experimental design to evaluate a six-session peer group intervention for HIV prevention among rural adults in Malawi . Two rural districts were r and omly assigned to intervention and control conditions . Independent r and om sample s of community adults compared the districts at baseline and at 6 and 18 months postintervention . Using multiple regressions controlling for six demographic factors , intervention district adults had significantly more favorable outcomes at 6- and 18-month evaluations for condom attitudes , self-efficacy for community prevention , self-efficacy for practicing safer sex , partner communication , using condoms ever in the past 2 months , and community prevention activities . Knowledge and hope for controlling the epidemic were significantly higher in the intervention district only at the 6-month evaluation ; having a recent HIV test was significantly higher only at 18 months . Levels of stigma and the number of risky sex practice s did not decrease when demographic factors were controlled . Exp and ing peer group intervention for HIV prevention would benefit rural adults The purpose of this study was to evaluate the impact of a mass-education campaign on knowledge , attitudes and practice of people leaving in Lagos State , Nigeria . A pre- and post-intervention survey was conducted among 6000 respondents from 116 administrative wards r and omly selected from all the 20 Local Government Areas ( LGA ) in Lagos State ( 300 respondents per LGA ) in January 2002 to document the effect of a series of communication interventions on the prevention of HIV/AIDS implemented between May and December 2001 in the state and to describe the changes that may have occurred in the knowledge base , attitude , beliefs and practice s. The result showed that the level of knowledge is relatively high as indicated in both the pre- and post-intervention survey , though there was a gain in knowledge in some areas after the intervention . Respondent 's practice s as they relate to issues that cause the spread of the disease did not change significantly after the intervention . The study demonstrated that mass campaigns using multiple channels can be effective in HIV/AIDS prevention , with the observed positive change and the sustained level of awareness A community intervention trial was undertaken in KwaZulu Natal , South Africa to evaluate the effectiveness of a high school drama-in-education programme . Seven pairs of secondary schools were r and omized to receive either written information about HIV/AIDS or the drama programme . Question naire surveys of knowledge , attitude and behaviour were compared before and 6 months after the interventions . One thous and and eighty students participated in the first survey and 699 in the second . Improvements in knowledge ( P=0.0002 ) and attitudes ( P<0.00001 ) about HIV/AIDS were demonstrated in pupils at schools receiving the drama programme when compared to pupils receiving written information alone . These changes were independent of age , gender , school or previous sexual experience . In schools receiving the drama programme , sexually active pupils reported an increase in condom use ( P<0.01 ) . It is important to provide re sources to sustain such programmes and to obtain stronger evidence of effect on behaviour by measuring changes in HIV incidence The evaluation of the Department of Educations ' life skills program on HIV and AIDS prevention among Grade 9 students in 22 r and omly allocated schools in KwaZulu-Natal , South Africa , showed only a significant increase in student knowledge about HIV/AIDS in the intervention group compared with the control group . No effects were found on safe sex practice s ( condom use , sexual intercourse ) or on measures of psychosocial determinants of these practice s ( attitude and self-efficacy ) . A process evaluation among the teachers showed that some implemented the program fully ( seven schools ) and some partially ( four schools ) . An exploratory analysis showed that students who received the full intervention were more positive in their perceptions about sexual behavior and social connectedness ( at 10-month follow-up ) and reported less sex and more condom use ( at 6-month follow-up ) than students in the partial and control groups . These limited effects therefore call for further analysis of the content and implementation strategies used in the classroom The nongovernmental organization , Uyisenga N'Manzi ( UNM ) , provides Rw and an orphans of genocide and HIV/AIDS with education , social , and mental health services . Many orphans in UNM report symptoms of psychological trauma . The primary study objective was to evaluate a multidisciplinary program integrating HIV prevention with an existing package of mental health services . We r and omly selected 120 orphans between ages 15 - 25 years served by UNM and evaluated sexually-transmitted infections , HIV risk-taking behaviors and knowledge , and mental health at baseline , 5 , 9 , and 12 months . Increased trauma symptoms at baseline were associated with poorer coping skills and social functioning , and increased psychological distress and HIV risk-taking behavior . Following the 12-month intervention , trauma symptoms declined significantly , with those accessing counseling services showing greatest improvement . Orphans with the highest trauma scores benefited most from the intervention . In this at-risk population , addressing mental health issues in the context of HIV prevention is critical Background : The HIV epidemic has a devastating impact among South African women . The current study evaluated the efficacy of SISTA South Africa , a culturally congruent HIV intervention for isiXhosa women in South Africa , which was adapted from SISTA , an HIV intervention for African American women . Methods : A r and omized-controlled trial recruited 342 isiXhosa women aged 18–35 years . Participants were r and omized to the general health comparison or the SISTA South Africa intervention . Xhosa-speaking peer health educators tailored the SISTA South Africa curriculum , while maintaining the core elements of the original SISTA intervention . Participants completed assessment s at baseline and 6 months follow-up . Results : Relative to participants in the comparison , participants in the HIV intervention reduced the frequency of unprotected vaginal intercourse acts ( adjusted mean difference = 1.06 ; P = 0.02 ) , were more likely to report not desiring dry sex ( adjusted odds ratio = 0.229 ; 95 % confidence interval = 0.10 to 0.47 ; P = 0.0001 ) , and were more likely to perceive that their main sexual partner did not desire dry sex ( adjusted odds ratio = 0.24 ; 95 % confidence interval = 0.11 to 0.52 ; P = 0.0001 ) . In addition , women r and omized to the intervention also reported an increase in HIV knowledge , greater relationship control , and had more opposing attitudes toward HIV stigma . The HIV intervention did not reduce sexually transmitted infection incidence . Conclusions : This trial demonstrates that an HIV intervention , which is adapted to enhance its gender and cultural relevance for rural isiXhosa women , can reduce self-reported sexual risk behaviors and enhance mediators of HIV among this vulnerable population Background HIV-awareness programs tailored toward the needs of rural communities are needed . We sought to quantify change in HIV knowledge in three rural Nigerian villages following an integrated culturally adapted and technology assisted educational intervention . Methods A prospect i ve 14-week cohort study was design ed to compare short-term changes in HIV knowledge between seminar-based education program and a novel program , which capitalized on the rural culture of small-group oral learning and was delivered by portable digital-audio technology . Results Participants were mostly Moslem ( 99 % ) , male ( 53.5 % ) , with no formal education ( 55 % ) . Baseline HIV knowledge was low ( < 80 % correct answers for 9 of the 10 questions ) . Knowledge gain was higher ( p < 0.0001 for 8 of 10 questions ) in the integrated culturally adapted and technology-facilitated ( n = 511 ) compared with the seminar-based ( n = 474 ) program . Conclusions Baseline HIV-awareness was low . Culturally adapted , technology-assisted HIV education program is a feasible cost-effective method of raising HIV awareness among low-literacy rural communities |
12,412 | 31,205,510 | Conclusions : Although FOLFIRINOX was associated with slightly longer median OS in more studies , the differences , when available , were not statistically significant . | Background : No clinical trial has directly compared nab-paclitaxel/gemcitabine ( nab-P/G ) with FOLFIRINOX ( fluorouracil/leucovorin/oxaliplatin/irinotecan ) in metastatic or advanced pancreatic cancer ( mPC or aPC ) .
We conducted a systematic review of real-world studies comparing these regimens in the first-line setting . | BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group , as compared with 3.7 months in the gemcitabine group ( hazard ratio for disease progression or death , 0.69 ; 95 % CI , 0.58 to 0.82 ; P<0.001 ) ; the response rate according to independent review was 23 % versus 7 % in the two groups ( P<0.001 ) . The most common adverse events of grade 3 or higher were neutropenia ( 38 % in the nab-paclitaxel-gemcitabine group vs. 27 % in the gemcitabine group ) , fatigue ( 17 % vs. 7 % ) , and neuropathy ( 17 % vs. 1 % ) . Febrile neutropenia occurred in 3 % versus 1 % of the patients in the two groups . In the nab-paclitaxel-gemcitabine group , neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days . CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma , nab-paclitaxel plus gemcitabine significantly improved overall survival , progression-free survival , and response rate , but rates of peripheral neuropathy and myelosuppression were increased . ( Funded by Celgene ; Clinical Trials.gov number , NCT00844649 . ) Purpose FOLFIRINOX ( FFN ) , nab-paclitaxel plus gemcitabine ( GN ) , and gemcitabine are three systemic therapies that provide clinical ly meaningful benefit to patients with unresectable pancreatic cancer ( UPC ) . There are no clinical trials that directly compare the efficacy of all three regimens . In this study , we aim to examine and compare the real-world effectiveness of these treatments . Methods Patients diagnosed with UPC who initiated palliative chemotherapy from August 2014 to January 2016 at any one of six cancer centers in British Columbia were identified from the provincial pharmacy . Clinical , pathological , treatment , and outcome characteristics were compared . Results Two hundred twenty-five patients were included : 55 % men , 68 % Eastern Cooperative Oncology Group 0/1 , 58 % metastatic disease . Patients who received FFN were younger ( p < 0.001 ) and in better performance status ( p < 0.001 ) . Patients treated with FFN or GN experienced significantly longer median overall survival ( OS ) when compared to those treated with gemcitabine ( 14.1 vs 10.5 vs 4.2 months , respectively , p < 0.001 ) . Progression-free survival ( PFS ) was also longer among patients on FFN or GN in comparison to gemcitabine ( FFN , HR 0.44 , 95 % CI 0.24 to 0.814 , p = 0.008 ; GN , HR 0.30 , 95 % CI 0.19 to 0.47 , p < 0.001 ) . A significantly higher proportion of patients require two or more dose modifications on FFN ( 40 % ) compared to GN ( 14 % ) or gemcitabine ( 9 % ) ( p < 0.001 ) . Conclusions Receipt of modified FFN and GN portends a better prognosis than gemcitabine alone . In the absence of a r and omized comparison of all three regimens , our population -based study reveals that the introduction of modified FFN and GN confers real-world effectiveness for UPC patients PURPOSE Gemcitabine plus nanoparticle albumin-bound ( NAB ) paclitaxel ( GA ) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma ( PDAC ) and a Karnofsky performance status ( PS ) of 70 % or greater . Because of the low number of patients with reduced PS , the efficacy of this regimen in fragile patients remains unclear . This study aim ed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS . PATIENTS AND METHODS In the phase I part of this study , patients were r and omly assigned to one of the following four parallel GA treatment arms ( six patients per arm ) : a biweekly schedule of NAB-paclitaxel ( 150 mg/m2 [ arm A ] or 125 mg/m2 [ arm C ] ) plus gemcitabine 1,000 mg/m2 or a st and ard schedule of 3 weeks on and 1 week off of NAB-paclitaxel ( 100 mg/m2 [ arm B ] or 125 mg/m2 [ arm D ] ) plus gemcitabine 1,000 mg/m2 . The two regimens with the better tolerability profile on the basis of predefined criteria were evaluated in the phase II part of the study , the primary end point of which was 6-month actuarial survival . RESULTS Arms B and D were selected for the phase II part of the study . A total of 221 patients ( 111 patients in arm B and 110 patients in arm D ) were enrolled . Baseline characteristics including median age ( 71 and 68 years in arms B and D , respectively ) , sex ( 51 % and 55 % men in arms B and D , respectively ) , and metastatic disease ( 88 % and 84 % in arms B and D , respectively ) were comparable between arms . The most frequent grade 3 or 4 toxicities in arms B and D were anemia ( 12 % and 7 % , respectively ) , neutropenia ( 32 % and 30 % , respectively ) , thrombocytopenia ( 7 % and 11 % , respectively ) , asthenia ( 14 % and 16 % , respectively ) , and neurotoxicity ( 11 % and 16 % , respectively ) . In arms B and D , there were no significant differences in response rate ( 24 % and 28 % , respectively ) , median progression-free survival ( 5.7 and 6.7 months , respectively ) , and 6-month overall survival ( 63 % and 69 % , respectively ) . CONCLUSION NAB-paclitaxel administered at either 100 and 125 mg/m2 in combination with gemcitabine on days 1 , 8 , and 15 every 28 days is well tolerated and results in acceptable safety and efficacy in patients with metastatic pancreatic ductal adenocarcinoma and a poor PS BACKGROUND Among patients with metastatic pancreatic cancer , combination chemotherapy with fluorouracil , leucovorin , irinotecan , and oxaliplatin ( FOLFIRINOX ) leads to longer overall survival than gemcitabine therapy . We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer . METHODS We r and omly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen ( oxaliplatin [ 85 mg per square meter of body‐surface area ] , irinotecan [ 180 mg per square meter , reduced to 150 mg per square meter after a protocol ‐specified safety analysis ] , leucovorin [ 400 mg per square meter ] , and fluorouracil [ 2400 mg per square meter ] every 2 weeks ) or gemcitabine ( 1000 mg per square meter on days 1 , 8 , and 15 every 4 weeks ) for 24 weeks . The primary end point was disease‐free survival . Secondary end points included overall survival and safety . RESULTS At a median follow‐up of 33.6 months , the median disease‐free survival was 21.6 months in the modified‐FOLFIRINOX group and 12.8 months in the gemcitabine group ( stratified hazard ratio for cancer‐related event , second cancer , or death , 0.58 ; 95 % confidence interval [ CI ] , 0.46 to 0.73 ; P<0.001 ) . The disease‐free survival rate at 3 years was 39.7 % in the modified‐FOLFIRINOX group and 21.4 % in the gemcitabine group . The median overall survival was 54.4 months in the modified‐FOLFIRINOX group and 35.0 months in the gemcitabine group ( stratified hazard ratio for death , 0.64 ; 95 % CI , 0.48 to 0.86 ; P=0.003 ) . The overall survival rate at 3 years was 63.4 % in the modified‐FOLFIRINOX group and 48.6 % in the gemcitabine group . Adverse events of grade 3 or 4 occurred in 75.9 % of the patients in the modified‐FOLFIRINOX group and in 52.9 % of those in the gemcitabine group . One patient in the gemcitabine group died from toxic effects ( interstitial pneumonitis ) . CONCLUSIONS Adjuvant therapy with a modified FOLFIRINOX regimen led to significantly longer survival than gemcitabine among patients with resected pancreatic cancer , at the expense of a higher incidence of toxic effects . ( Funded by R&D Unicancer and others ; Clinical Trials.gov number , NCT01526135 ; EudraCT number , 2011‐002026‐52 . |
12,413 | 28,195,640 | There is no evidence of a difference between subcutaneous versus intravenous UFH for preventing VTE recurrence , VTE-related or all-cause mortality , and major bleeding .
There is also no evidence of a difference between subcutaneous UFH and LMWH for preventing VTE recurrence , VTE-related or all-cause mortality or major bleeding | BACKGROUND Venous thromboembolism ( VTE ) is a prevalent and serious condition .
Its medical treatment requires anticoagulation , usually with either unfractionated or low molecular weight heparin ( LMWH ) .
Administration of unfractionated heparin ( UFH ) is usually intravenous ( IV ) but can be subcutaneous as well .
This is an up date of a review first published in 2009 .
OBJECTIVES To assess the effects of subcutaneous UFH versus intravenous UFH , subcutaneous LMWH or any other anticoagulant drug for the initial treatment of venous thromboembolism . | 54 patients with venographically verified deep venous thrombosis ( DVT ) were r and omized to treatment with either intravenous infusions of 240 anti-Xa U/kg/12 h unfractionated heparin ( UFH ) or 240 or 120 anti-Xa U/kg/12 h of the low molecular weight heparin Fragmin . Repeated venographies showed improvement in 48 % of the UFH-treated patients and 50 and 77 % , respectively , in the Fragmin-treated patients . Progression was seen only in the UFH-treated patients and was observed in 11 % . Two bleeding complications were seen in the Fragmin group in 2 patients receiving the very high dose of 240 anti-Xa U/kg/12 h. Anti-Xa activity in plasma and activated partial thromboplastin time ( APTT ) does not correlate in the Fragmin-treated patients . Fragmin was as effective as UFH in preventing the progress of thrombosis in DVT . In another study 120 anti-Xa U/kg Fragmin given subcutaneously 2 times daily to 13 patients with DVT result ed in adequate anti-Xa activity but with a tendency for accumulation of the Fragmin-induced activity . Subcutaneous injections of Fragmin 2 times daily also appears to prevent the progression of thrombosis effectively INTRODUCTION Trials comparing the use of full dose unfractionated heparin ( UFH ) or low molecular weight heparins ( LMWHs ) in very elderly patients with impaired renal function are lacking . IRIS aim ed to assess whether LMWH is at least as safe as UFH in this population . MATERIAL S AND METHODS The study included renally impaired patients ≥70 years with acute symptomatic lower limb deep vein thrombosis ( DVT ) . Patients were r and omized to initial treatment with either tinzaparin 175 IU/kg once daily ( n=269 ) or activated partial thromboplastin time-adjusted UFH twice daily ( n=270 ) . After acute management both groups received vitamin K antagonist to day 90 . RESULTS The trial was stopped prematurely due to a difference in mortality favoring the UFH group ( 11.5 vs. 6.3 % ; p=0.035 ) . Rates of clinical ly relevant bleedings by day 90 were similar in the tinzaparin ( 11.9 % ) and UFH ( 11.9 % ) groups , as were rates of confirmed recurrent venous thromboembolism ( VTE ) ( 2.6 vs. 1.1 % ; p=0.34 ) . As the mortality difference could not be explained by bleedings or recurrent VTE , a post-hoc analysis was performed . This identified six baseline characteristics significantly correlated with mortality , of which five were over-represented in the tinzaparin group . CONCLUSION The IRIS study was a challenging study involving patients ( mean age 83 years ) usually excluded from clinical studies , but its early termination has left questions unanswered . The mortality difference observed with tinzaparin vs. UFH in elderly , renally-impaired patients with DVT can not be explained on the basis of bleedings or recurrent VTE , and may reflect an imbalance of mortality risk factors at baseline Intravenous heparin followed by oral anticoagulant therapy ( e. g. with coumarin ) is still the most widely used treatment for deep venous thromboembolism . Self-administered subcutaneous injections of heparin have been thought of as a promising alternative to coumarin , but the high doses required for ongoing prophylaxis have raised concerns about the possible development of bone disease . Certainly , long-term heparin therapy has been reported to cause osteoporosis in both laboratory animals and humans . This study aim ed to compare the efficacy and safety of unfractionated ( UF ) heparin with that of a low molecular weight heparin ( Fragmin , Kabi Pharmacia ) in the prevention of recurrent deep venous thrombosis ( DVT ) and pulmonary embolism ( PE ) in a consecutive series of patients with contraindications to coumarin therapy . The patients comprised 40 men and 40 women , aged between 19 and 92 years ( mean age , 68 years ) . They had all previously been diagnosed as having acute DVT and had been treated with conventional doses of heparin while in hospital . All patients had at least one of the following conditions : recent blood loss ( either spontaneous or during admission while receiving heparin therapy ) ; active gastroduodenal ulcer disease ; psychological or physical inability or unwillingness to underst and and accept the need for regular laboratory monitoring during coumarin treatment ; chronic alcoholism ; dementia ; pregnancy ; recent neurosurgery , and pericardial effusion ; or were over 80 years of age . They were r and omly allocated to receive either UF heparin , 10,000 IU s.c . b.d . , or Fragmin , 5000 IU anti-Factor Xa s.c . b.d . , for a period of 3 - 6 months . ( ABSTRACT TRUNCATED AT 250 WORDS Low molecular weight heparin fractions have been demonstrated as efficient as low doses of st and ard heparin in preventing post-operative deep-vein thrombosis . Several clinical studies are , now , carrying out in patients with acute deep-vein thrombosis in order to assess efficacy and safety of low molecular weight heparin fractions as compared to st and ard heparin . In a r and omised study including patients with deep-vein thrombosis treated either with low molecular weight heparin or with subcutaneously st and ard heparin , we demonstrated an effectiveness , in terms of thrombus reduction , of low molecular weight heparin as well as st and ard heparin . However , low molecular weight heparin seemed to be safer than st and ard heparin STUDY OBJECTIVE To determine the efficacy and safety of adjusted subcutaneous calcium heparin compared with continuous intravenous calcium heparin as the initial treatment for acute deep vein thrombosis . DESIGN R and omized control trial . SETTING University-affiliated general hospital . PATIENTS Of 111 consecutive patients considered , 103 had acute proximal or calf vein thrombosis confirmed by ascending venography and met all other eligibility criteria . INTERVENTIONS PATIENTS were r and omly assigned to receive subcutaneous or intravenous heparin . The subcutaneous regimen consisted of an initial dose of 15,000 U , adjusted thereafter to prolong the activated partial thromboplastin time to 50 to 70 seconds . The continuous intravenous regimen was begun as a bolus injection of 5000 U , followed by an infusion of 1250 U/h , adjusted to maintain the activated partial thromboplastin time at 50 to 70 seconds . MEASUREMENTS AND MAIN RESULTS There was no significant difference in the rate of new pulmonary embolism between the two groups , as defined by new high-probability defect on repeat ventilation-perfusion scintigrams of the lung in 96 ( 93 % ) of the patients after 7 to 10 days of treatment . Five of forty-seven patients in the subcutaneous group and 5 of 49 in the intravenous group developed pulmonary embolism ( 95 % confidence interval [ CI ] for the difference , -13.1 % to 12.2 % ) . Similarly , there was no significant difference in the frequency of hemorrhagic complications . Five of fifty-one patients in the subcutaneous group and 5 of 52 in the intravenous group had hemorrhagic complications ( 95 % CI for the difference , -11.2 % to 11.6 % ) . CONCLUSION Adjusted subcutaneous calcium heparin may be an effective and safe alternative to continuous intravenous calcium heparin in the initial treatment of acute proximal deep vein thrombosis Summary Two studies have been done to establish recommendations for dosage and dose adjustment in the treatment of deep vein thrombosis ( DVT ) with low molecular weight heparin ( LMWH ) . In the first , 56 patients were r and omized in a double blind study to be treated either with unfractionated heparin ( UFH ) or LMWH s. c. every 12 h. Initial doses were given according to age and sex , disregarding bodyweight , and the dose was then adjusted when the peak plasma heparin concentration fell outside the desired range of 0.5–0.8 anti-FXa U/ml . There were fewer dose adjustments in the LMWH group . The correlation between injected dose ( U/kg bodyweight ) and the heparin concentration was higher in the LMWH group ( r=0.59 ) than in the UFH group ( r=0.38 ) . The results suggest that , in order to obtain the desired heparin concentration , the initial dose of LMWH should be about 100 U/kg bodyweight every 12 h . In the second , open study , this dosage plan was followed in 15 patients . The peak heparin concentration on Day 2 ranged from 0.40 to 0.75 anti-FXa U/ml and adjustment was only required in 3 patients . Day to day variation in peak heparin activity in the individual patient varied little ( CV 11–22 % ) , and there was no accumulation . The results indicate that plasma heparin concentration is more predictable using LMWH than UFH , and they point to definite advantages in the use of LMWH in a bodyweight adjusted dosage Ninety-four patients with deep vein thrombosis of inferior limbs were r and omly allocated to receive sodium heparin either by subcutaneous injections or by continuous intravenous infusion for six days . No significant difference was observed in the therapeutic efficiency as judged by phlebographic examinations and in rate of symptomatic pulmonary embolism between the two groups . There was one instance of major bleeding in the subcutaneous group . Minor bleedings occurred in 10 of the 48 patients treated with subcutaneous heparin and in 13 of the 46 patients receiving intravenous heparin . The results showed that subcutaneous injections of sodium heparin are as effective and safe as continuous intravenous infusion of this drug in the treatment of deep vein thrombosis BACKGROUND Few reports have addressed the value of unfractionated heparin ( UFH ) or low-molecular-weight heparin in treating the full spectrum of patients with venous thromboembolism ( VTE ) , including recurrent VTE and pulmonary embolism . METHODS In an open , multicenter clinical trial , 720 consecutive patients with acute symptomatic VTE , including 119 noncritically ill patients ( 16.5 % ) with pulmonary embolism and 102 ( 14.2 % ) with recurrent VTE , were r and omly assigned to treatment with subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm ( preceded by an intravenous loading dose ) , or fixed-dose ( adjusted only to body weight ) subcutaneous nadroparin calcium . Oral anticoagulant therapy was started concomitantly and continued for at least 3 months . We recorded the incidence of major bleeding during the initial heparin treatment and that of recurrent VTE and death during 3 months of follow-up . RESULTS Fifteen ( 4.2 % ) of the 360 patients assigned to UFH had recurrent thromboembolic events , as compared with 14 ( 3.9 % ) of the 360 patients assigned to nadroparin ( absolute difference between rates , 0.3 % ; 95 % confidence interval , -2.5 % to 3.1 % ) . Four patients assigned to UFH ( 1.1 % ) and 3 patients assigned to nadroparin ( 0.8 % ) had episodes of major bleeding ( absolute difference between rates , 0.3 % ; 95 % confidence interval , -1.2 % to 1.7 % ) . Overall mortality was 3.3 % in each group . CONCLUSIONS Subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm is as effective and safe as fixed-dose nadroparin for the initial treatment of patients with VTE , including those with pulmonary embolism and recurrent VTE One hundred patients with phlebographically proved acute deep vein thrombosis of the legs were prospect ively r and omised into two treatment groups to compare the safety and efficacy of subcutaneous calcium heparin versus intravenous sodium heparin administered by constant infusion pump . The dose of heparin was determined by daily measurement of the kaolin cephalin clotting time . Treatment was maintained for up to 14 days , after which phlebography was repeated . Of 49 patients who received subcutaneous calcium heparin , two showed an increase in thrombus size , while eight showed complete lysis . In the 47 patients who received intravenous sodium heparin thrombus increased in size in 13 while only one showed evidence of complete lysis . These differences were significant . There were no significant differences between the two groups in the incidence of serious complications , although almost half of those receiving intravenous heparin had some minor problem with the constant infusion pump and just over half of those receiving subcutaneous heparin had some bruising at the injection site . This study showed that subcutaneous calcium heparin was more effective in helping lyse existing thrombus and preventing its propagation than intravenous sodium heparin 48 patients with acute deep venous thrombosis of the lower limbs were treated with sodium heparin . In 23 patients heparin was injected subcutaneously ( s.c . ) twice a day and in 25 patients heparin was given by continuous intravenous perfusion ( i.v . ) . Pain and edema disappeared after 8.7 days ( s.c . ) and 11.7 days ( i.v . ) respectively . One non fatal pulmonary embolism occurred in each group . A second venography was performed in 24 patients after 7 days of treatment and revealed no difference between the two groups . As judged by repeated thrombin time determination , anticoagulation was ineffective on at least one day in 39 % of patients treated subcutaneously and in 60 % of patients treated intravenously . The two pulmonary embolisms occurred in patients with ineffective anticoagulation . It is concluded that heparin may be used either intravenously or subcutaneously in the treatment of acute deep venous thrombosis . Thromboembolic complications occurred with both methods of treatment when anticoagulation was ineffective Prothrombin fragments ( F1 + 2 ) , thrombin-antithrombin complexes ( TAT ) and D-dimers , markers of hemostatic system activation , were measured in 59 consecutive patients with deep vein thrombosis ( DVT ) . Patients were r and omly treated either with subcutaneous unfractionated heparin ( UH ) administered in two to three subcutaneous doses adjusted to activated partial thromboplastin time ( APTT ) or with low-molecular weight heparin ( LMWH ) ( dalteparin ) administered in a fixed dose of 200 IU/kg body weight in one subcutaneous injection daily . Before treatment , F1 + 2 , TAT and D-dimer were above the cut-off level in 27/59 ( 46 % ) , 34/59 ( 58 % ) and all ( 100 % ) patients , respectively . Significant associations were observed between F1 + 2 and TAT ( r=.66 , P<.001 ) , TAT and D-dimer ( r=.36 , P<.005 ) and F1 + 2 and D-dimer ( r=.30 , P<.050 ) . On the third day of treatment , F1 + 2 and TAT significantly decreased to reference values in almost all patients ( in 64/66 determinations of both F1 + 2 and TAT ) and remained low on the seventh day of treatment . Compared to pretreatment values , a nonsignificant decrease of D-dimer was noted in both groups , but all values remained above the cut-off value . When markers of hemostatic system activation in the UH and LMWH groups were compared , no significant differences were observed . It was concluded that subcutaneous UH in an APTT-adjusted dose and subcutaneous LMWH in a once-daily weight-adjusted dose controlled these markers of hemostatic system activation in a similar manner 271 patients with acute symptomatic deep venous thrombosis of lower limbs , confirmed by strain-gauge plethysmography and /or venography , were r and omly assigned to receive intermittent subcutaneous heparin calcium or heparin sodium by continuous intravenous infusion for 6 - 10 days . Heparin dosage was adjusted to maintain activated partial thromboplastin time values ( Thrombofax reagent ) at 1.3 - 1.9 times the basal ones . Strain-gauge plethysmography was repeated at the end of heparin treatment , and evaluation of therapy was performed by comparing the indexes of venous hemodynamics and by assessing the incidence of pulmonary embolism and of bleeding complications . In the intravenous group , Maximal Venous Outflow ( MVO ) increased from 20.8 + /- 12.8 to 28.4 + /- 17.5 ml/min per 100 ml of tissue and Venous Capacitance ( VC ) from 1.39 + /- 0.92 to 1.94 + /- 1.0 ml/100 ml of tissue ( mean + /- SD ) . In the subcutaneous group , MVO increased from 21.0 + /- 12.7 to 27.5 + /- 18.1 and VC from 1.60 + /- 0.86 to 2.06 + /- 1.0 . The median improvement of MVO and VC were 22 % and 36 % respectively in the IV group and 20 % and 24 % in the SC group . Clinical pulmonary embolism occurred in 2 patients in the intravenous group ( 1 fatal ) and in 4 in the subcutaneous group ( 1 fatal ) . 9 major bleeding complications occurred in the intravenous group ( 1 fatal ) and 5 in the subcutaneous group ( 1 fatal ) . The differences were not significant at the statistical analysis . The results suggest that subcutaneous intermittent heparin has a comparable efficacy to continuous intravenous heparin in the treatment of deep venous thrombosis . To the same conclusion points an overview of the seven r and omized trials which compared these treatment modalities We performed a r and omized double-blind trial comparing continuous intravenous heparin with intermittent subcutaneous heparin in the initial treatment of 115 patients with acute proximal deep-vein thrombosis . Intermittent subcutaneous heparin as administered in this trial was inferior to continuous intravenous heparin in preventing recurrent venous thromboembolism . The subcutaneous heparin regimen induced an initial anticoagulant response below the target therapeutic range in the majority of patients and result ed in a high frequency of recurrent venous thromboembolism ( 11 of 57 patients , 19.3 percent ) , which was virtually confined to patients with a subtherapeutic anticoagulant response . In contrast , continuous intravenous heparin induced a therapeutic anticoagulant response in the majority of patients and a low frequency of recurrent events ( 3 of 58 patients , 5.2 percent ; P = 0.024 ) ; the recurrences were limited to patients with an initial subtherapeutic anticoagulant response . The results of this trial establish the efficacy of intravenous heparin in the treatment of proximal venous thrombosis and suggest a relation between the effectiveness of heparin and the levels of anticoagulation achieved ; such a relation could explain the observed failure of the subcutaneous regimen St and ard treatment with heparin followed by vitamin K antagonists is frequently complicated by bleeding and recurrent venous thromboembolism ( VTE ) in cancer patients with VTE . To compare the efficacy , safety and overall survival of long-term idraparinux treatment to st and ard therapy in cancer patients we conducted a post-hoc analysis in the subgroup of non-active and active cancer patients included in the Van Gogh DVT clinical trial . The cancer patients with deep venous thrombosis ( DVT ) and without pulmonary embolism ( PE ) were r and omised to st and ard treatment or a once-weekly subcutaneous injection of idraparinux ( 2.5 mg ) , a synthetic pentasaccharide . 421 cancer patients were included . A total of 220 patients received idraparinux and 201 were allocated to st and ard therapy for three months ( 8 % ) or six months ( 92 % ) . A recurrent VTE was observed during the first six months in 2.5 % ( n=5 ) of the idraparinux recipients compared to 6.4 % ( n=12 ) in the st and ard therapy group ( hazard ratio 0.39 , 95 % confidence interval [ CI ] ; 0.14 - 1.11 ) . The rate of bleeding was comparable ( odds ratio 0.89 , 95 % CI ; 0.50 - 1.59 ) . The outcomes were similar at three months after r and omisation in all patients . Of the idraparinux recipients , 22.7 % ( n=50 ) died during the study period compared to 48 patients ( 23.9 % ) in the st and ard treatment group ( hazard ratio 0.99 , 95 % CI ; 0.66 - 1.48 ) . In conclusion , no significant safety or survival differences were observed between cancer patients with DVT treated with idraparinux for six months compared to st and ard therapy . Fewer recurrent VTEs were observed in the idraparinux group ; however , this was not statistically significant and also because of study limitations this should be interpreted with caution OBJECTIVE To evaluate whether low-molecular-weight heparin ( LMWH ) could be equally ( or more ) effective than oral anti-vitamin-K agents ( AVK ) in the long-term treatment of deep venous thrombosis ( DVT ) . DESIGN A r and omised , open-label trial . MATERIAL AND METHODS In this trial , 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included . After initial LMWH , patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol . The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism ( VTE ) . Duplex scans were performed at 6 and 12 months . RESULTS During the 12-month period , six patients ( 5 % ) of 119 who received LMWH and 13 ( 10.7 % ) of 122 who received AVK had recurrent VTE ( p=0.11 ) . In patients with cancer , recurrent VTE tended to be lower in the LMWH group ( two of 36 [ 5.5 % ] ) vs. seven of 33 [ 21.2 % ] ; p=0.06 ) . One major bleeding occurred in the LMWH group and three in the AVK group . Venous re-canalisation increased significantly at 6 months ( 73.1 % vs. 47.5 % ) and at 12 months ( 91.5 % vs. 69.2 % ) in the LMWH group . CONCLUSIONS Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi . Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE , especially in patients with cancer In this study , 294 patients with acute proximal DVT ( deep venous thrombosis ) were r and omly assigned to receive intravenous st and ard heparin in the hospital ( 98 patients ) or low-molecular-weight heparin ( LMWH ) ( nadroparin 0.1 mL [ equivalent to 100 AXa IU ] per kg of body weight subcutaneously twice daily ) administered primarily at home ( out patients ) or alternatively in hospital ( 97 patients ) or subcutaneous calcium heparin ( SCHep ) ( 99 patients , 0.5 mL bid ) administered directly at home . The study design allowed out patients taking LMWH heparin to go home immediately and hospitalized patients taking LMWH to be discharged early . Patients treated with st and ard heparin or LMWH received the oral anticoagulant starting on the second day , and heparin was discontinued when the therapeutic range ( INR 2 - 3 ) had been reached . Anticoagulant treatment was maintained for 3 months . Patients treated with SCHep were injected twice daily for 3 months without oral anticoagulants . Patients were evaluated for inclusion and follow-up with color duplex scanning . Venography was not used . In case of suspected pulmonary embolism ( PE ) a ventilatory-perfusional lung scan was performed . Endpoints of the study were recurrent or extension of DVT , bleeding , the number of days spent in hospital , and costs of treatments . Of the 325 patients included , 294 completed the study . Dropouts totaled 31 ( 10.5 % ) ; six of the 325 included patients ( 1.8 % ) died from the related , neoplastic illness . Recurrence or extension of DVT was observed in 6.1 % of patients in the LMWH group , in 6.2 % in the st and ard heparin group , and in 7.1 % in the SCHep group . Most recurrences ( 11/17 ) were in the first month in all groups . Bleedings were all minor , mostly during hospital stay . Hospital stay in patients treated with LMWH was 1.2 ± 1.4 days in comparison with 5.4 ± 1.2 in those treated with st and ard heparin . There was no hospital stay in the SCHep group . Average treatment costs in 3 months in the st and ard heparin group ( US $ 2,760 ) were considered to be 100 % ; in comparison costs in the LMWH group was 28 % of the st and ard heparin and 8 % in the SCHep group . This study indicated that LMWH and SCHep can be used safely and effectively to treat patients with proximal DVT at home at a lower cost BACKGROUND AND OBJECTIVES The optimal treatment of superficial thrombophlebitis of the leg is undefined . The main study objective was to assess the efficacy and safety of unmonitored high doses as compared to low doses of unfractionated heparin ( UFH ) for prevention of venous thromboembolic complications in patients with superficial thrombophlebitis of the thigh . DESIGN AND METHODS Sixty consecutive patients with acute thrombophlebitis of the great saphenous vein , as assessed by ultrasonography , were r and omized to subcutaneous injection twice daily of UFH in high unmonitored doses ( 12,500 IU for one week followed by 10,000 IU ) or prophylactic doses ( 5,000 IU ) for four weeks . The rate of asymptomatic involvement of the deep venous system and /or symptomatic thromboembolic events during a six-month follow-up period was assessed and compared between the two study groups . RESULTS Six of the 30 patients ( 20.0 % ; 95 % CI , 7.7 to 38.6 ) r and omized to low-dose UFH developed symptomatic or asymptomatic events as compared to 1 of the 30 patients ( 3.3 % ; 95 % CI , 0.07 to 17.2 ) who received high-dose UFH ( p=0.05 by one-sided Fisher 's exact test ) . No patient experienced major bleeding complications in either group . INTERPRETATION AND CONCLUSIONS The results of this study suggest that in patients with acute thrombophlebitis of the thigh unmonitored high doses of UFH are more effective than prophylactic doses of UFH for prevention of venous thromboembolic complications and do not enhance the risk of bleeding complications The low dose heparin regimen ( LDH ) is not appropriate for prevention of intra- and postoperative thromboembolic complications in high risk patients , especially those undergoing elective hip replacement . Despite LDH prophylaxis , the incidence of deep-vein thrombosis ( DVT ) remains in a range of 20 to 35 % . Adjusted-dose unfractionated heparin prophylaxis is thought to be one of the most effective regimens for thrombosis prophylaxis in this indication , but it requires two or three daily injections as well as precise monitoring of the activated partial thromboplastin time ( aPTT ) . As an attractive alternative , we investigated the efficacy and safety of the low molecular weight heparin ( LMWH ) certoparin combined with dihydroergotamine ( DHE ) given once daily . In a r and omised , open clinical trial , a total number of 305 patients undergoing total elective hip replacement were enrolled and divided into two groups , either receiving a fixed-dose combination of LMWH ( 3,000 IU ) and DHE ( 0.5 mg ) subcutaneously once daily , or adjusted-dose unfractionated heparin ( UFH ) subcutaneously every 8 h. The UFH dosage was adjusted daily to keep an aPTT of about 50 s. The aPTT was determined 3 h after the morning injection . During the study , the starting dose ( 15,000 IU/day ) was increased to a plateau value of 28,800 + /- 7,150 IU/day ( mean + /- SD ) to maintain the aPTT in the prescribed range . The plateau value was achieved after 8 postoperative days . For analysis of efficacy 289 patients were evaluable . The occurrence of deep vein thrombosis was determined by bilateral ascending venography , which was performed on the same day in patients with clinical signs suggesting DVT ; and in all remaining patients at the end of the prophylaxis period . Deep vein thrombosis was diagnosed in 17 of 142 patients ( 12.0 % ) treated with LMWH/DHE and in 13 of 147 patients ( 8.8 % ) treated with adjusted-dose UFH . Combined distalproximal thrombosis was more frequently in patients receiving UFH ( n = 5 ; 3.4 % ) compared to the LMWH/DHE group ( n = 2 ; 1.4 % ) . These differences are statistically not significant . In the UFH group one case of non-fatal pulmonary embolism occurred . Both prophylaxis regimens were well tolerated ; wound bleeding was observed in 8 ( 5.3 % ) patients in the LMWH group and in 6 ( 4.0 % ) patients in the UFH group . Intraoperative blood-loss volume ( mean + /- SD ) was 751 + /- 339 mL ( LMWH/DHE ) and 736 + /- 380 mL ( UFH ) , whereas postoperative drain-loss volume ( mean + /- SD ) was found to be 523 + /- 333 mL ( LMWH/DHE ) and 581 + /- 404 mL ( UFH ) . Whole blood transfusion volumes ( mean + /- SD ) were 570 + /- 202 mL ( LMWH/DHE ) and 748 + /- 455 mL ( UFH ) . Additionally , red cell replacement volumes ( mean + /- SD ) were 804 + /- 435 mL ( LMWH/DHE ) and 720 + /- 328 mL ( UHF ) . Revision of wound or additional drainage were necessary in 3 LMWH/DHE and 7 UFH patients . One patient needed reoperation due to bleeding , 3 ( 2.0 % ) had petechia and 1 exhibited an allergic exanthema , all of them in the UFH group . A slight erythema at the injection site was observed in 6 ( 3.9 % ) patients receiving LMWH/DHE . During the course of prophylaxis , injection hematomas were documented in 57.9 % ( LMWH/DHE ) and in 61.4 % ( UFH ) of the patients . All differences were statistically not significant . Single daily subcutaneous injections of LMWH/DHE appeared to be safe and efficacious compared to adjusted-dose UFH for prophylaxis of DVT in high-risk patients In a prospect i ve multicenter trial , 149 consecutive patients with phlebographically proven proximal and /or distal deep vein thrombosis of the leg were r and omly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 ( Fraxiparine ) in a fixed dose or unfractionated heparin ( UFH ) in doses adjusted according to the activated partial thromboplastin time . Pre- and post-treatment phlebograms were assessed blindly using the Arnesen 's score system in 134 patients available for analysis of the treatment efficacy . The mean phlebographic score after 10 days of treatment was significantly decreased in both groups ( p less than 0.001 ) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant . There was an improvement in 45/68 patients ( 66 % ) in the Fraxiparine group and in 32/66 patients ( 48 % ) in the UFH group , and an increase in the thrombus size in 10/68 ( 15 % ) and 12/66 ( 18 % ) , respectively . One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group . During a follow-up period of 3 months , two rethromboses had occurred in the UFH group and none in the Fraxiparine group . It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis In the initial treatment of venous thromboembolism ( VTE ) fondaparinux , a pentasaccharide , is a good alternative to heparin . Whether this is also true for cancer patients is unknown . We performed two post-hoc analyses of two r and omized studies to compare efficacy , safety and overall survival of fondaparinux to st and ard initial ( low-molecular-weight ) heparin ( LMWH ) treatment in cancer patients with venous thromboembolism . Two hundred thirty-seven cancer patients with deep venous thrombosis ( DVT ) were initially treated with fondaparinux or enoxaparin . Two hundred forty cancer patients with pulmonary embolism ( PE ) received fondaparinux or unfractionated heparin . The initial treatment was followed by vitamin K antagonists . In DVT patients , the three-month recurrence rate was 5.4 % in the enoxaparin recipients compared to 12.7 % in those treated with fondaparinux [ absolute difference 7.3 % , 95 % CI 0.1 , 14.5 ] . A recurrence was observed in 8.9 % of the PE patients treated with fondaparinux compared to 17.2 % in the unfractionated heparin recipients [ absolute difference -8.3 , 95 % CI -16.7 , 0.1 ] . In both studies no difference in bleeding and overall survival was observed . Regarding overall survival and bleeding fondaparinux is comparable to enoxaparin and unfractionated heparin in cancer patients . No significant differences in recurrent VTE were observed when comparing fondaparinux with unfractionated or LMWH . Because of study limitations these results should be considered hypothesis-generating Abstract The efficacy and safety of two methods of heparin administration was investigated ; 100 patients with calf vein thrombosis were r and omly allocated to receive either subcutaneous ( SC ) or intravenous ( IV ) heparin for seven days . Venography was performed in each patient to confirm the exact size and site of thrombus and was repeated at the end of heparin treatment . IV heparin was administered using a constant infusion pump . The dose of heparin to be administered was determined by daily estimation of KCCT . In SC group , thrombi increased in size in 2 % , remained unchanged in 50 % and decreased in 48 % . In the IV group , they increased in size in 20 % , were unchanged in 62 % and decreased in 18 % . The difference in decreases in size was significant ( Sixty-eight patients with acute deep vein thrombosis were allocated at r and om to two treatment groups . One group ( n = 33 ) received a fixed dose of 750 anti-Xa units of a low molecular weight heparin ( CY 222 Choay Institute ) ; the other group ( n = 35 ) received st and ard heparin in doses of 500 IU/kg/24 h. Both treatments were given for 10 days in two daily subcutaneous injections . A second phlebography was performed on the last day of treatment . No haemorrhagic complication was observed in the group treated with CY 222 , as opposed to three cases of haemorrhage in the group treated with st and ard heparin . The initial phlebographic score and the location of deep vein thrombotic lesions were the same in both groups . Angiographic improvement , with more than 30 % thrombolysis , was obtained at the end of treatment in 64 % of patients in the CY 222 group and in 65 % of patients in the st and ard heparin group ( NS ) . In 2 patients treated with st and ard heparin the second phlebography showed extension of the thrombosis . The initial score remained unchanged in 1/3 of patients in both groups . The activated partial thromboplastin time was prolonged ( 2 or 3 fold the normal value ) in the st and ard heparin group and unchanged in the CY 222 group . Anti-Xa activity was significantly higher in the CY 222 group than in the st and ard heparin group . It is concluded that CY 222 and st and ard heparin were equally effective in patients with deep vein thrombosis . However , haemorrhagic complications were more frequent with st and ard heparin that with CY 222 Forty-one patients with clinical indications for heparin therapy were r and omized to receive continuous intravenous heparin sodium therapy or intermittent ( four-hourly bolus ) heparin therapy , with control by the activated partial thromboplastin time . Seven of 21 patients receiving intermittent therapy had major bleeding episodes , whereas none of the 20 patients receiving continuous heparin therapy had major bleeding ( P = .005 ) . One patient on continuous therapy had a pulmonary embolus , while none on intermittent therapy had recurrent thromboembolism . Two heavily bleeding patients on intermittent therapy were switched to continuous treatment after bleeding was controlled . The use of continuous heparin therapy appears significantly safer with regard to hemorrhagic complications than the use of intermittent therapy One-hundred and forty-one patients with clinical signs of acute deep venous thrombosis ( DVT ) in the legs were r and omly allocated to receive heparin either as two daily subcutaneous injections ( s.c . ) or as continuous intravenous infusion ( i.v . ) . The thrombi extended into the popliteal or femoral veins in 83 % of the patients . Verification of diagnosis and evaluation of therapy was performed by phlebography , plethysmography and thermography . The results showed that heparin administered s.c . twice daily was as efficient as continuous i.v . infusion in preventing extension of the thrombus . In two patients the s.c . administration was stopped due to local haematomas at the injection sites . Retroperitoneal or intramuscular bleedings occurred in four patients , two in each group . Two major , non-fatal pulmonary emboli occurred , one in each group Abstract Purpose Current guidelines recommend the use of low molecular weight heparin ( LMWH ) for most haemodynamically stable patients with pulmonary thromboembolism ( PTE ) , however , it is not clear whether LMWH is preferable to unfractionated heparin ( UFH ) for the treatment of massive PTE . We aim ed to compare the use of LMWH versus UFH after thrombolytic treatment in the management of acute massive PTE for hemorrhage and hospital mortality . Methods The study , a r and omized , single center , parallel design trial , included the patients who had confirmed the diagnosis of massive PTE according to clinical findings and computerized thorax angiography and no contraindication to the treatment between January 2011 and October 2013 . After thrombolytic treatment , the patients assigned to therapy with LMWH or UFH . Any hemorrhage , major hemorrhage , and hospital mortality were assessed . Results A total of 121 patients , 71 female ( 58.7 % ) and 50 male ( 41.3 % ) , who had massive PTE with an average age 62.6 ± 15.7 ( ranges 22–87 ) were included for analyses in the study . They were allocated to either LMWH ( n = 60 ) or UFH ( n = 61 ) group . Although the occurrence of any adverse event ( 21.7 vs 27.9 % ) and each individual type of adverse event were all lower in the LMWH group compared to UFH group ( 6.7 vs 11.5 % , 3.3 vs 9.8 % , and 15.0 vs 19.7 % for death , major hemorrhage , and any hemorrhage , respectively ) , the differences were not statistically significant . Conclusions Our findings suggest that LMWH might be a better option in the management of the patients with massive PTE . Multi-center larger r and omized controlled trials are required to confirm our results Twenty-eight patients with the diagnosis of deep vein thrombosis ( DVT ) were subjected to a prospect i ve , r and omized study comparing continuous and intermittent heparin treatment , utilizing the same doses and duration of therapy . The effect on pain ( estimated with a scoring system ) and the antithrombotic effect ( assessed by the inhibition of 125I-fibrinogen accretion ) , followed for one week , were unrelated . Pulmonary embolism was scored and studied from lung perfusion scans and chest X-rays . A high frequency was found in both groups . The therapeutic efficacy and side-effects did not differ between the two treatment groups . Bleeding , preferentially from vein puncture ( post-phlebography ) , was more common in women , while a heparin-induced elevation of serum aminotransferases ( S-ALAT adn S-ASAT ) ( in 2/3 of the patients ) was not related to age , sex or bleeding complications In a double-blind study , patients with phlebographically proven deep venous thrombosis ( DVT ) were treated with subcutaneous injections twice a day of either unfractionated heparin ( UH ; n = 27 ) or low molecular weight heparin ( LH ; n = 29 ) for 7 days , and the dose was adjusted until therapeutic range was reached , according to a chromogenic substrate anti-Xa assay . Forty-eight percent of the LH group did not need dose adjustment as compared to 24 % of the UH group . During the course of heparin administration , deviation from initial heparin activity was frequent in both groups , but mean activity did not indicate a cumulative effect in either group . There was 1 incidence of pulmonary embolism ( LH ) and only 1 minor bleeding episode ( UH ) . Half of the patients in both groups were phlebographically improved . We conclude that subcutaneous heparin treatment with UH or LH appears safe and convenient |
12,414 | 21,563,171 | In 14 of the 39 trials evaluating generic interventions , the program interventions demonstrated significantly greater reductions in alcohol use either through a main or subgroup effect .
Gender , baseline alcohol use , and ethnicity modified the effects of interventions .
This review identified studies that showed no effects of preventive interventions , as well as studies that demonstrated statistically significant effects .
There was no easily discernible pattern in characteristics that would distinguish trials with positive results from those with no effects .
Most commonly observed positive effects across programs were for drunkenness and binge drinking .
Current evidence suggests that certain generic psychosocial and developmental prevention programs can be effective and could be considered as policy and practice options . | BACKGROUND Alcohol misuse in young people is cause of concern for health services , policy makers , prevention workers , criminal justice system , youth workers , teachers , parents .
This is one of three review s examining the effectiveness of ( 1 ) school-based , ( 2 ) family-based , and ( 3 ) multi-component prevention programs .
OBJECTIVES To review evidence on the effectiveness of universal school-based prevention programs in preventing alcohol misuse in school-aged children up to 18 years of age . | AIMS Despite widespread prevention efforts to decrease adolescent risk-taking , substance use and driving after drinking ( DD ) are prevalent in the United States . The current study compared the efficacy of an abbreviated version of Drug Abuse and Resistance Education ( DARE-A ) to a new Risk Skills Training Program ( RSTP ) . DESIGN Adolescent participation in drinking , drug use , DD and riding with a drunk driver was examined longitudinally . After baseline assessment s , adolescents were r and omly assigned to the RSTP . DARE-A or a no intervention control group and then completed 2-month post-test and 6-month follow-up assessment s. SETTING Adolescents attended a mid-sized suburban high school . PARTICIPANTS The sample ( N = 300 ) was comprised of 58 % females and the age range was 14 - 19 years . INTERVENTION The RSTP was developed to target several risk behaviors and to examine the feasibility of conducting a brief personalized prevention program in a group setting . DARE-A focused on increasing knowledge and underst and ing the deleterious effects of substance use . MEASUREMENTS Risk-taking behavior , perception of peer risk-taking and positive and negative alcohol expectancies were assessed . FINDINGS RSTP participants decreased participation in several risk behaviors at post-test , but reductions were not maintained at 6-month follow-up . The control and DARE-A groups increased their positive and decreased their negative alcohol expectancies . The control group increased their alcohol consumption . CONCLUSIONS Results suggest that a brief , personalized , group prevention program is a feasible approach to reducing adolescent risk-taking . Strategies must be developed to solidify these positive changes so that they are longer-lasting OBJECTIVE To evaluate the effect of the middle and junior high school Drug Abuse Resistance Education ( D.A.R.E. ) and D.A.R.E. Plus programs on drug use and violence . DESIGN R and omized controlled trial of 24 schools , with 3 conditions : D.A.R.E. only , D.A.R.E. Plus , and delayed program control . SETTING Schools and neighborhoods , primarily in Minneapolis-St Paul . PARTICIPANTS All seventh- grade students in 24 schools in the academic year 1999 - 2000 ( N = 6237 at baseline , 67.3 % were white , and there was 84.0 % retention at final follow-up ) . INTERVENTIONS The middle and junior high school D.A.R.E. curriculum in the 16 schools that received D.A.R.E. only and D.A.R.E. Plus . In the 8 schoolts that received D.A.R.E. Plus , additional components included a peer-led parental involvement classroom program called " On the VERGE , " youth-led extracurricular activities , community adult action teams , and postcard mailings to parents . The interventions were implemented during 2 school years , when the cohort was in the seventh and eighth grade s. MAIN OUTCOME MEASURES Self-reported tobacco , alcohol , and marijuana use ; multidrug use ; violence ; and victimization , assessed at the beginning and end of seventh grade and at the end of eighth grade . Growth curve analytic methods were used to assess changes over time by condition . RESULTS There were no significant differences between D.A.R.E. only and the controls ; significant differences among boys between D.A.R.E. Plus and controls for tobacco , alcohol , and multidrug use and victimization ; significant differences among boys between D.A.R.E. Plus and D.A.R.E. only in tobacco use and violence ; and no significant behavioral differences among girls . CONCLUSION D.A.R.E. Plus significantly enhanced the effectiveness of the D.A.R.E. curriculum among boys and was more effective than the delayed program controls , underscoring the potential for multiyear , multicomponent prevention programs and demonstrating sex differences in response to intervention programs This study examined the effects of the Iowa Strengthening Families Program ( ISFP ) and the Preparing for the Drug-Free Years program ( PDFY ) on young adolescent transitions from nonuse of substances to initiation and progression of substance use . Analyses incorporated 3 waves of data collected over a 2.5-year period from 329 rural young adolescents . Outcomes were analyzed by using log-linear models that incorporated substance use status frequencies derived from latent transition analyses . Effects on delayed substance use initiation were shown for both the ISFP and the PDFY at a 2-year follow-up . Also at this follow-up , the PDFY showed effects on delayed progression of use among those previously reporting initiation This study examined long-term follow-up data from a large-scale r and omized trial to determine the extent to which participation in a school-based drug abuse prevention program during junior high school led to less risky driving among high school students . Self-report data collected from students in the 7th , 10th , and 12th grade s were matched by name to students ' department of motor vehicles ( DMV ) records at the end of high school . The DMV data included the total number of violations on students ' driving records as well as the number of “ points ” that indicate the frequency and severity of the violations . A series of logistic regression analyses revealed that males were more likely to have violations and points on their driving records than females , and regular alcohol users were more likely to have violations and points than those who did not use alcohol regularly . Controlling for gender and alcohol use , students who received the drug prevention program during junior high school were less likely to have violations and points on their driving records relative to control group participants that did not receive the prevention program . Findings indicated that antidrinking attitudes mediated the effect of the intervention on driving violations , but not points . These results support the hypothesis that the behavioral effects of competence-enhancement prevention programs can extend to risk behaviors beyond the initial focus of intervention , such as risky driving Abstract . Objective : The authors assessed short-term effectiveness of a Web-based alcohol education program on entering freshmen . Participants : 3,216 incoming first-year students were r and omized to a control or intervention group . Methods : Controls completed a survey and knowledge test the summer before college ; 4 to 6 weeks after arrival on campus , they completed a follow-up survey of behaviors and harms followed by an invitation to complete the online course . Intervention students completed the precourse survey and test , the online course , and final exam prior to coming to campus . This was followed by a survey 4 to 6 weeks after arrival on campus . Results : Although the intervention group showed significantly higher alcohol-related postcourse knowledge compared to the control group , protective behavior , risk-related behavior , high-risk drinking , and alcohol-related harm did not favor the intervention group , with the sole exception of playing drinking games . Conclusions : Alcohol knowledge alone was insufficient to mitigate alcohol-related high-risk behaviors in this student population AIM To evaluate the effectiveness of a school-based substance abuse prevention program developed in the EU-Dap study ( EUropean Drug Addiction Prevention trial ) . MATERIAL S AND METHODS Cluster R and omized Controlled Trial . Seven European countries participated in the study ; 170 schools ( 7079 pupils 12 - 14 years of age ) were r and omly assigned to one of three experimental conditions or to a control condition during the school year 2004/2005 . The program consisted of a 12-h curriculum based on a comprehensive social influence approach . A pre-test survey assessing past and current substance use was conducted before the implementation of the program , while a post-test survey was carried out about 18 months after the pre-test . The association between program condition and change in substance use at post-test was expressed as adjusted prevalence odds ratio ( POR ) , estimated by multilevel regression models . RESULTS Persisting beneficial program effects were found for episodes of drunkenness ( any , POR=0.80 ; 0.67 - 0.97 ; frequent , POR=0.62 ; 0.47 - 0.81 ) and for frequent cannabis use in the past 30 days ( POR=0.74 ; 0.53 - 1.00 ) , whereas daily cigarette smoking was not affected by the program as it was at the short-term follow-up . Baseline non-smokers that participated in the program progressed in tobacco consumption to a lower extent than those in the control condition , but no difference was detected in the proportion of quitters or reducers among baseline daily smokers . CONCLUSION The experimental evaluation of an innovative school curriculum based on a comprehensive social influence approach , indicated persistent positive effects over 18 months for alcohol abuse and for cannabis use , but not for cigarette smoking We report the results of a growth model analysis of the impact of a Family Empowerment Intervention ( FEI ) on the heavy drinking over a 36-month follow-up period among youths processed at the Hillsborough County Juvenile Assessment Center . Families involved in the project were r and omly assigned to either receive an Extended Services Intervention ( ESI ) or the FEI . Families in the ESI group received monthly phone contacts and , if indicated , referral information ; FEI families received three one-hour , home-based meetings per week for approximately 10 weeks from a clinician-trained paraprofessional . By seeking to improve family functioning by empowering parents , it was hypothesized that target youths ' behavior and psychosocial functioning would improve . Although the difference between FEI and ESI was not significant , the reported frequency of getting very high or drunk on alcohol declined more over time for FEI completers than FEI noncompleters . The results provide support for the impact of the FEI services Abstract Preparing for the Drug-Free Years ( PDFY ) is a curriculum design ed to help parents learn skills to consistently communicate clear norms against adolescent substance use , effectively and proactively manage their families , reduce family conflict , and help their children learn skills to resist antisocial peer influences . This study examined the effects of PDFY on the trajectories of these factors , as well as on the trajectory of alcohol use from early to mid adolescence . The sample consisted of 424 rural families of sixth grade rs from schools r and omly assigned to an intervention or a control condition . Data were collected from both parents and students at pretest , posttest , and 1- , 2- and 3 $ $ \frac{1}{2}$$ -year follow-ups . Latent growth models were examined . PDFY significantly reduced the growth of alcohol use and improved parent norms regarding adolescent alcohol use over time . Implication s for prevention and evaluation are discussed This study examined whether the efficacy of keepin ’ it REAL , a model program for substance use prevention in schools , was moderated by gender , ethnicity , and acculturation . Gender differences in program efficacy may arise through boys ' higher risk of drug use , inadequate attention to girls ' developmental issues , or cultural factors like polarized gender expectations . Data came from a r and omized trial in 35 Phoenix , Arizona , middle schools involving 4,622 mostly Latino 7th grade rs . Using multi-level mixed models and multiple imputation missing techniques , results for the total sample showed no gender differences in program effects on recent substance use , but the program was more effective in fostering boys ' than girls ' anti-drug norms . Subgroup analyses demonstrated several more beneficial program effects for boys than girls ( less alcohol and cigarette use and stronger anti-drug norms ) , but only among less acculturated Latinos . There were no gender differences in program effects among more acculturated Latinos , nor among non-Latino whites The authors evaluated the efficacy of a brief image-based prevention intervention and assessed current drug use as a moderator of intervention effects . In a clinical trial , 416 high school-age adolescents were r and omized to either the brief intervention or usual care control , with data collected at baseline and 3-month follow-up . The brief intervention consisted of a tailored in-person communication and a series of parent/guardian print material s based on the behavior-image model . Health behavior goal setting increased for participants receiving the brief intervention , with an effect size in the small range ( d = 0.33 ) . Overall effect sizes for cigarette smoking frequency and quantity and alcohol use frequency and quantity were small ( ds = 0.16 - 0.21 ) and in favor of the brief intervention . However , adolescents reporting current substance use who received the brief intervention reduced their frequency and heavy use of alcohol , frequency and quantity of cigarette smoking , and reported fewer alcohol/drug problems , with larger effects ranging from small to approaching medium in size ( ds = 0.32 - 0.43 , ps < .01 ) . This study suggests that brief image-based messages may increase health behavior goal setting and reduce substance use , particularly among drug-using older adolescents PURPOSE School-based substance abuse prevention programs are widespread but are rarely evaluated in Europe . We aim ed to evaluate the effect of a new school-based prevention program against substance use on the frequency of alcohol consumption and alcohol-related problem behaviors among European students . METHODS During the school year 2004 - 2005 , a total of 7,079 students aged 12 - 14 years from 143 schools in seven European countries participated in this cluster r and omized controlled trial . Schools were r and omly assigned to either control ( 65 schools , 3,532 students ) or to a 12-session st and ardized program based on the comprehensive social influence model ( 78 schools , 3,547 students ) . Alcohol use and frequency of alcohol-related problem behaviors were investigated through a self-completed anonymous question naire at baseline and 18 months thereafter . The association between intervention and changes in alcohol-related outcomes was expressed as odds ratio ( OR ) , estimated by multilevel regression model . RESULTS The preventive program was associated with a decreased risk of reporting alcohol-related problems ( OR = .78 , 95 % confidence intervals [ CI ] = .63-.98 ) , although this reduction was not statistically significant in the subgroup of 743 current drinkers at baseline . The risk for alcohol consumption was not modified by exposure to the program ( OR = .93 , 95 % CI = .79 - 1.09 ) . In the intervention group , nondrinkers and occasional drinkers at baseline progressed toward frequent drinking less often than in the control group . CONCLUSIONS School curricula based on the comprehensive social-influence model can delay progression to frequent drinking and reduce occurrence of alcohol-related behavioral problems in European students . These results , albeit moderate , have potentially useful implication s at the population level This study examined the long-term impact of Preparing for the Drug Free Years ( PDFY ) on young adult alcohol abuse disorder , addressing theory-based questions about how , and for whom , the program had its effects on the outcomes . Participants were 429 families of 6th grade rs enrolled in 33 rural schools located in the Midwestern United States . Schools were r and omly assigned to conditions . Target adolescents ( 52 % female ) were interviewed periodically from age 11 to age 22 ; throughout adolescence , information was collected also from the youths ' parents . Moderation and mediation analyses were conducted using regression analysis and structural equation modeling with covariates measured at baseline ( age 11 ) , mediators measured at posttest ( age 12 ) , and the outcome measured at the young adult follow-up ( age 22 ) . Results showed that PDFY reduced the rate of alcohol abuse among target young women , with evidence that this effect was mediated by increased prosocial skills . The rate of alcohol abuse among PDFY group men was not significantly different from that of control group men . Findings have implication s for reducing the public health burden of alcohol abuse among young women OBJECTIVE To determine whether the addition of a parental monitoring intervention ( Informed Parents and Children Together [ ImPACT ] ) alone or with " boosters " could enhance ( either broaden or sustain or both ) the effect of a small group , face-to-face adolescent risk reduction intervention Focus on Kids ( FOK ) . METHODS A longitudinal , r and omized , community-based cohort study was conducted of 35 low-income , community-based , in-town setting s. A total of 817 black youths aged 12 to 16 years at baseline were studied . After completion of baseline measures , youths were r and omized to receive a face-to-face intervention alone ( FOK only ) , a face-to-face intervention and a parental monitoring intervention ( FOK plus ImPACT ) , or both of the above plus boosters ( FOK plus ImPACT plus boosters ) . Risk and protective behaviors were assessed at 6 and 12 months after intervention . RESULTS At 6 months ' follow-up , youths in families that were assigned to FOK plus ImPACT reported significantly lower rates of sexual intercourse , sex without a condom , alcohol use , and cigarette use and marginally lower rates of " risky sexual behavior " compared with youths in families that were assigned to FOK only . At 12 months after intervention , rates of alcohol and marijuana use were significantly lower and cigarette use and overall risk intention were marginally lower among FOK plus ImPACT youths compared with FOK only youths . With regard to the boosters delivered at 7 and 10 months , 2 risk behaviors -- use of crack/cocaine and drug selling -- were significantly lower among the youths who were assigned to receive the additional boosters compared with youths without the boosters . The rates of the other risk behaviors and intentions did not differ significantly . CONCLUSIONS The results of this r and omized , controlled trial indicate that the inclusion of a parental monitoring intervention affords additional protection from involvement in adolescent risk behaviors 6 and 12 months later compared with the provision of an intervention that targets adolescents only . At the same time , the results of the present study do not provide sufficient evidence that booster sessions further improve targeted behaviors enough to include them in a combined parent and youth intervention Reported are results of an independent effectiveness study of the Project ALERT drug prevention program implemented in eight Pennsylvania middle schools by outside program leaders employed by Cooperative Extension . In this r and omized , 2-cohort longitudinal evaluation , 1,649 seventh- grade students completed a pretest and four waves of posttests over the 2-year program and 1-year follow-up . Project ALERT 's effectiveness was tested through a 3-level hierarchical linear model . Analyses failed to yield any positive effects for substance use or mediators for use in the adult or teen-assisted delivery of the curriculum . An extensive set of additional analyses detected no differential program effects by student risk level , gender , school , or level of implementation quality . Potential explanations for outcomes relative to Project ALERT 's original effectiveness trial are discussed , as well as implication s for future research , including the need to conduct independent effectiveness studies of previously vali date d programs in a variety of context AIMS The School Health and Alcohol Harm Reduction Project ( SHAHRP study ) aim ed to reduce alcohol-related harm in secondary school students . DESIGN The study used a quasi-experimental research design in which r and omly selected and allocated intervention and comparison groups were assessed at eight , 20 and 32 months after baseline . SETTING Metropolitan , government secondary schools in Perth , Western Australia . PARTICIPANTS The sample involved over 2300 students . The retention rate was 75.9 % over 32 months . INTERVENTION The evidence -based intervention , a curriculum programme with an explicit harm minimization goal , was conducted in two phases over a 2-year period . MEASURES Knowledge , attitude , total alcohol consumption , risky consumption , context of use , harm associated with own use and harm associated with other people 's use of alcohol . FINDINGS There were significant knowledge , attitude and behavioural effects early in the study , some of which were maintained for the duration of the study . The intervention group had significantly greater knowledge during the programme phases , and significantly safer alcohol-related attitudes to final follow-up , but both scores were converging by 32 months . Intervention students were significantly more likely to be non-drinkers or supervised drinkers than were comparison students . During the first and second programme phases , intervention students consumed 31.4 % and 31.7 % less alcohol . Differences were converging 17 months after programme delivery . Intervention students were 25.7 % , 33.8 % and 4.2 % less likely to drink to risky levels from first follow-up onwards . The intervention reduced the harm that young people reported associated with their own use of alcohol , with intervention students experiencing 32.7 % , 16.7 % and 22.9 % less harm from first follow-up onwards . There was no impact on the harm that students reported from other people 's use of alcohol . CONCLUSIONS The results of this study support the use of harm reduction goals and classroom approaches in school drug education School-based drug prevention curricula constitute the nation ’s most prevalent strategy to prevent adolescent drug use . We evaluated the effects of one such curriculum , Project ALERT , on adolescent substance use . In particular , we sought to determine if a single effect on 30-day alcohol use , noted shortly following the completion of the 2-year program , could be detected 1 year later . We also looked for delayed effects on other outcomes of interest , namely lifetime alcohol use , and 30-day and lifetime use of cigarettes , marijuana , and inhalants . We employed a r and omized controlled trial that used school as the unit of assignment . Thirty-four schools with grade s 6–8 from 11 states completed the study . Seventy-one Project ALERT instructors taught 11 core lessons to sixth grade rs and 3 booster lessons to seventh grade rs . Students were assessed prior to the onset of the intervention , as sixth grade rs , after the completion of the 2-year curriculum , as seventh grade rs , and again 1 year later as eighth grade rs . This paper examines data from the pretest and final posttest . Using hierarchical nonlinear modeling , we found that our earlier effect on 30-day alcohol use did not persist . Further , we continued to find no effects for lifetime alcohol use and both the lifetime and 30-day use of cigarettes , marijuana , and inhalants . Our findings do not support the long-term effectiveness of Project ALERT , when delivered to sixth grade rs OBJECTIVE To provide a review of the evidence from 3 experimental trials of Project Towards No Drug Abuse ( TND ) , a senior-high-school-based drug abuse prevention program . METHODS Theoretical concepts , subjects , design s , hypotheses , findings , and conclusions of these trials are presented . A total of 2,468 high school youth from 42 schools in southern California were surveyed . RESULTS The Project TND curriculum shows reductions in the use of cigarettes , alcohol , marijuana , hard drugs , weapon carrying , and victimization . Most of these results were replicated across the 3 trials . CONCLUSION Project TND is an effective drug and violence prevention program for older teens , at least for one-year follow-up OBJECTIVE This study aim ed to examine the effects of a school-based alcohol education intervention . DESIGN Two-arm three-wave cluster-r and omized controlled trial , with schools as the unit for r and omization . Surveys were conducted prior to intervention implementation , then 4 and 12 months after baseline . SETTING A total of 30 public schools in Schleswig-Holstein , Germany . Participants Baseline data were obtained from 1686 7th grade rs . The retention rate was 85 % over 12 months . Intervention The intervention consisted of four interactive lessons conducted by teachers , booklets for students and booklets for parents . MEASURES Knowledge , attitudes , life-time alcohol consumption ( ever use alcohol without parental knowledge , ever been drunk and ever binge drinking ) and past-month alcohol use . RESULTS Intention-to-treat analyses revealed that intervention status was associated with more general knowledge about alcohol and lower levels of life-time binge drinking . No effects were found with respect to students ' self-reported attitudes , intentions to drink , life-time alcohol use and past-month alcohol use . CONCLUSIONS The results indicate that this brief school-based intervention had a small short-term preventive effect on alcohol misuse This study reports findings on a combined family and school-based competency-training intervention from an in-school assessment 2.5 years past baseline , as a follow-up to an earlier study of substance initiation . Increased rates of observed alcohol use and an additional wave of data allowed evaluation of regular alcohol use and weekly drunkenness , with both point-in-time and growth curve analyses . Thirty-six rural schools were r and omly assigned to ( a ) a combined family and school intervention condition , ( b ) a school-only condition , or ( c ) a control condition . The earlier significant outcome on a substance initiation index was replicated , and positive point-in-time results for weekly drunkenness were observed , but there were no statistically significant outcomes for regular alcohol use . Discussion focuses on factors relevant to the mix of significant longitudinal results within a consistent general pattern of positive intervention-control differences to test early nutritional interventions and prospect i ve observational cohorts . RCTs are generally accepted as method ologically the best approach for informing health policy . They can equalise unknown as well as known confounding factors and so can demonstrate causation ; they permit estimation of effect size and so can be used to assess likely A r and omized experimental test of the implementation feasibility and the efficacy of a culturally adapted Parent Management Training intervention was conducted with a sample of 73 Spanish-speaking Latino parents with middle-school-aged youth at risk for problem behaviors . Intervention feasibility was evaluated through weekly parent satisfaction ratings , intervention participation and attendance , and overall program satisfaction . Intervention effects were evaluated by examining changes in parenting and youth adjustment for the intervention and control groups between baseline and intervention termination approximately 5 months later . Findings provided strong evidence for the feasibility of delivering the intervention in a larger community context . The intervention produced benefits in both parenting outcomes ( i.e. , general parenting , skill encouragement , overall effective parenting ) and youth outcomes ( i.e. , aggression , externalizing , likelihood of smoking and use of alcohol , marijuana , and other drugs ) . Differential effects of the intervention were based on youth nativity status This study used Complier Average Causal Effect analysis ( CACE ; see G. Imbens & D. Rubin , 1997 ) to examine the impact of an adaptive approach to family intervention in the public schools on rates of substance use and antisocial behavior among students ages 11 - 17 . Students were r and omly assigned to a family-centered intervention ( N = 998 ) in 6th grade and offered a multilevel intervention that included ( a ) a universal classroom-based intervention , ( b ) the Family Check-Up ( selected ; T. J. Dishion & K. Kavanagh , 2003 ) , and ( c ) family management treatment ( indicated ) . All services were voluntary , and approximately 25 % of the families engaged in the selected and indicated levels . Participation in the Family Check-Up was predicted by 6th- grade teacher ratings of risk , youth reports of family conflict , and the absence of biological fathers from the youths ' primary home . Relative to r and omized matched controls , adolescents whose parents engaged in the Family Check-Up exhibited less growth in alcohol , tobacco , and marijuana use and problem behavior during ages 11 through 17 , along with decreased risk for substance use diagnoses and police records of arrests by age 18 This study evaluated the impact of two targeted family sessions focused on driving issues delivered within the context of the Raising Healthy Children project . The Raising Healthy Children project began in the fall of 1993 , drawing students in the 1st or 2nd grade s from 10 schools . Schools were assigned to an intervention or control condition , and the school-wide , family- and student-focused preventive intervention to address developmentally salient risk and protective factors was delivered during elementary and middle school . The family driving sessions were administered to families in the intervention condition prior to and after teenagers received their driver 's license . The first session consisted of a home visit with families design ed to help parents and their children improve decision-making skills concerning driving and to develop clear st and ards and expectations regarding driving-related behavior . A second session , at the time of licensure , was design ed to help parents and teens develop a written contract that stated family expectations , a plan for monitoring compliance with these expectations , and consequences for compliance or non-compliance . Consistent with the study 's group-r and omized design , intervention effects were assessed with multi-level logistic regression models in which students were grouped by their original school assignment . These models assessed specific effects of the driving sessions by adjusting for control variables measured when students were in 8th grade , prior to the driving sessions . Results indicated that students in the intervention group were more likely than students in the control group to report that they had a written driving contract ( p = .003 , OR = 4.98 ) , and had participated in making the driving rules in the family ( p = .025 , OR = 1.70 ) . Further , students in the intervention group reported significantly fewer risky behaviors including driving under the influence of alcohol ( p = .021 , OR = .45 ) and driving with someone who had been drinking ( p = .038 , OR = .56 ) BACKGROUND Universal school-based prevention programs for alcohol , tobacco , and other drug use are typically design ed for all students within a particular school setting . However , it is unclear whether such broad-based programs are effective for youth at high risk for substance use initiation . METHOD The effectiveness of a universal drug abuse preventive intervention was examined among youth from 29 inner-city middle schools participating in a r and omized , controlled prevention trial . A sub sample of youth ( 21 % of full sample ) was identified as being at high risk for substance use initiation based on exposure to substance-using peers and poor academic performance in school . The prevention program taught drug refusal skills , antidrug norms , personal self-management skills , and general social skills . RESULTS Findings indicated that youth at high risk who received the program ( n = 426 ) reported less smoking , drinking , inhalant use , and polydrug use at the one-year follow-up assessment compared to youth at high risk in the control condition that did not receive the intervention ( n = 332 ) . Results indicate that a universal drug abuse prevention program is effective for minority , economically disadvantaged , inner-city youth who are at higher than average risk for substance use initiation . CONCLUSIONS Findings suggest that universal prevention programs can be effective for a range of youth along a continuum of risk BACKGROUND The Good Behavior Game ( GBG ) , a method of classroom behavior management used by teachers , was tested in first- and second- grade classrooms in 19 Baltimore City Public Schools beginning in the 1985 - 1986 school year . The intervention was directed at the classroom as a whole to socialize children to the student role and reduce aggressive , disruptive behaviors , confirmed antecedents of later substance abuse and dependence disorders , smoking , and antisocial personality disorder . This article reports on impact to ages 19 - 21 . METHODS In five poor to lower-middle class , mainly African American urban areas , three or four schools were matched and within each set r and omly assigned to one of three conditions : ( 1 ) GBG , ( 2 ) a curriculum- and -instruction program directed at reading achievement , or ( 3 ) the st and ard program . Balanced assignment of children to classrooms was made , and then , within intervention schools , classrooms and teachers were r and omly assigned to intervention or control . RESULTS By young adulthood significant impact was found among males , particularly those in first grade who were more aggressive , disruptive , in reduced drug and alcohol abuse/dependence disorders , regular smoking , and antisocial personality disorder . These results underline the value of a first- grade universal prevention intervention . REPLICATION : A replication was implemented with the next cohort of first- grade children with the same teachers during the following school year , but with diminished mentoring and monitoring of teachers . The results showed significant GBG impact for males on drug abuse/dependence disorders with some variation . For other outcomes the effects were generally smaller but in the predicted direction Raising Healthy Children ( RHC ) is a preventive intervention design ed to promote positive youth development by targeting developmentally appropriate risk and protective factors . In this study , the authors tested the efficacy of the RHC intervention on reducing adolescent alcohol , marijuana , and cigarette use . Ten public schools , which comprised 959 1st- and 2nd- grade students ( 54 % male students , 18 % minority , 28 % low socioeconomic status ) , were matched and assigned r and omly to either intervention or control conditions . A 2-part latent growth modeling strategy was used to examine change in both use-versus-nonuse and frequency-of-use outcomes while students were in Grade s 6 - 10 . Results indicated significant ( p < .05 ) intervention effects in growth trajectories for frequency of alcohol and marijuana use but not for use versus nonuse . These findings provide support for preventive interventions that take a social development perspective in targeting empirically supported risk and protective factors and demonstrate the use of 2-part models in adolescent substance use research In 1985 the Division of Mental Health , World Health Organization , Geneva , convened a group of investigators from centers in four countries -- Australia , Chile , Norway , Swazil and --to participate in a pilot study on the efficacy of school-based alcohol education . The goal of the educational program was to delay onset and minimize involvement of alcohol use among 13- to 14-year-old adolescents . Twenty-five schools in the four countries , representing middle- and lower-class population s , were r and omly assigned to peer-led education , teacher-led education , or a control condition . The educational program was derived from social-psychological theory and etiological research on adolescent alcohol use . The program focused on the social and environmental influences to drink alcohol and skills to resist those influences . It consisted of five lessons over 2 months . Baseline and posttest data measured alcohol use knowledge , attitudes , skills , and friends ' drinking patterns . Data were collected immediately prior to and 2 months following the educational program . The data converge on the finding that peer-led education appears to be efficacious in reducing alcohol use across a variety of setting s and cultures This paper reports on the evaluation of a culturally grounded prevention intervention targeting substance use among urban middle-school students . The curriculum consists of 10 lessons promoting antidrug norms and teaching resistance and other social skills , reinforced by booster activities and a media campaign . Three versions were delivered : Mexican American , combined African American and European American , and Multicultural . Thirty-five middle schools were r and omly assigned to 1 of the 3 versions or the control . Students completed baseline and follow-up question naires over a 2-year period ( total 6,035 respondents ) . Analyses utilizing a generalized estimating equations approach assessed the overall effectiveness of cultural grounding and the cultural matching hypothesis . Support was found for the intervention 's overall effectiveness , with statistically significant effects on gateway drug use as well as norms , attitudes , and resistance strategies but with little support for the cultural matching hypothesis . Specific contrasts found the Mexican American and Multicultural versions impacted the most outcomes OBJECTIVE To determine whether office-based interventions change adolescents ' alcohol beliefs and alcohol use . DESIGN R and omized , controlled trial . SETTING Five managed care group practice s in Washington , DC . PARTICIPANTS Consecutive 12- to 17-year-olds ( N = 409 ) seeing primary care providers ( N = 26 ) for general check-ups . Most of the adolescents ( 79 % ) were African American , 44 % were male , and 16 % currently drank . INTERVENTIONS Usual care ( Group I ) , adolescent priming with alcohol self- assessment just prior to check-up ( Group II ) , adolescent priming and provider prompting with adolescent self- assessment and brochure ( Group III ) . MAIN OUTCOME MEASURES Adolescent alcohol beliefs at exit interview and self-reported behaviors at 6- and 12-month follow-up . RESULTS At exit interview , Groups II and III reported that less alcohol was needed for impaired thinking and a greater intent to drink alcohol in the next 3 months than Group I. At 6 months , Group III reported more resistance to peer pressure to drink , and Groups II and III reported more bingeing than Group I. At 1-year follow-up , controlling for baseline levels , Groups II ( odds ratio [ OR ] , 3.44 ; 95 % confidence interval [ CI ] , 1.44 - 6.24 ) and III ( OR , 2.86 ; CI , 1.13 - 7.26 ) reported more bingeing in the last 3 months than Group I. Group II reported more drinking in the last 30 days ( OR , 2.31 ; CI , 1.31 - 4.07 ) and in the last 3 months ( OR , 1.76 ; CI , 1.12 - 2.77 ) than Group I. CONCLUSION Brief office-based interventions were ineffective in reducing adolescent alcohol use but may increase adolescent reporting of alcohol use ABSTRACT This study tested the efficacy of brief image-based print-mediated parent/caregiver and adolescent messages integrating physical activity with alcohol use avoidance . A total of 684 high school students were r and omly assigned to either the parent postcard or adolescent flyer arm , with baseline and four-month postintervention data collection s. A significant repeated measures interaction ( group × time ) was found ( F(4,344 ) = 2.48 , p = .04 ) , with univariate tests showing less alcohol use frequency and problems ( ps < .05 ) among adolescents exposed to parent material s. Repeated measures factorial MANOVAs for group × time × prior current drug use were significant , with drug using adolescents receiving parent print messages showing less alcohol initiation and frequency and marijuana initiation and frequency ( ps < .05 ) . Very brief print material s sent to parents/caregivers may hold some promise for influencing substance use among adolescents , particularly those already using drugs This study evaluated the substance initiation effects of an intervention combining family and school-based competency-training intervention components . Thirty-six rural schools were r and omly assigned to 1 of 3 conditions : ( a ) the classroom-based Life Skills Training ( LST ) and the Strengthening Families Program : For Parents and Children 10 - 14 , ( b ) LST only , or ( c ) a control condition . Outcomes were examined 1 year after the intervention posttest , using a substance initiation index ( SII ) measuring lifetime use of alcohol , cigarettes , and marijuana and by rates of each individual substance . Planned intervention-control contrasts showed significant effects for both the combined and LST-only interventions on the SII and on marijuana initiation . Relative reduction rates for alcohol initiation were 30.0 % for the combined intervention and 4.1 % for LST only Background : Studies of effectiveness of school-based prevention of substance misuse have generally overlooked gender differences . The purpose of this work was to analyse gender differences in the effectiveness of a new European school-based curriculum for prevention of substance misuse among adolescents . Methods : The European Drug Abuse Prevention ( EU-Dap ) trial took place in seven European countries during the school year 2004–05 . Schools were r and omly assigned to either a control group or a 12-session st and ardised curriculum ( “ Unplugged ” ) based on a comprehensive social influence model . The analytical sample consisted of 6359 students ( 3324 boys and 3035 girls ) . The use of cigarettes , alcohol and illicit drugs , adolescents ’ knowledge and opinions about substances , as well as social and personal skills were investigated through a self-completed anonymous question naire administered at enrolment and 3 months after the end of the programme . Adjusted Prevalence Odds Ratios were calculated as the measure of association between the intervention and behavioural outcomes using multilevel regression modelling . Results : At enrolment , boys were more likely than girls to have used cannabis and illicit drugs , whereas girls had a higher prevalence of cigarette smoking . At the follow-up survey , a significant association between the programme and a lower prevalence of all behavioural outcomes was found among boys , but not among girls . Age and self-esteem emerged as possible modifiers of these gender differences , but effects were not statistically significant . Conclusions : Comprehensive social influence school curricula against substance misuse in adolescence may perform differently among girls and boys , owing to developmental and personality factors This study examines the effects of 2 brief family-focused interventions on the trajectories of substance initiation over a period of 6 years following a baseline assessment . The 2 interventions , design ed for general- population families of adolescents , were the 7-session Iowa Strengthening Families Program ( ISFP ) ( Molgaard & Spoth , 2001 ) and the 5-session Preparing for the Drug Free Years Program ( PDFY ) ( Catalano , Kosterman , Haggerty , Hawkins , & Spoth , 1999 ) . Thirty-three rural public schools were r and omly assigned to the ISFP , the PDFY , or a minimal-contact control condition . The authors evaluated the curvilinear growth observed in school-level measures of initiation using a logistic growth curve analysis . Alcohol and tobacco composite use indices -- as well as lifetime use of alcohol , cigarettes , and marijuana-- and lifetime drunkenness , were examined . Significant intervention-control differences were observed , indicating favorable delays in initiation in the intervention groups PURPOSE To assess the effects of r and om drug and alcohol testing ( DAT ) among high school athletes . METHODS This was a 2-year prospect i ve r and omized controlled study of a single cohort among five intervention high schools with a DAT policy and six schools with a deferred policy , serially assessed by voluntary , confidential question naires . DAT school athletes were at risk for r and om testing during the full academic year . Positive test results were reported to parents or guardians , with m and atory counseling . Indices of illicit drug use , with and without alcohol use , were assessed at the beginning and end of each school year for the past month and prior year . Potential mediating variables were evaluated . RESULTS Student-athletes from intervention and control schools did not differ in past 1-month use of illicit drug or a combination of drug and alcohol use at any of the four follow-up periods . At the end of the initial school year and after 2 full school years , student-athletes at DAT schools reported less drug use during the past year ( p < .01 ) compared to athletes at the deferred policy schools . Combining past year drug and alcohol use together , student-athletes at DAT schools reported less use at the second and third follow-up assessment s ( p < .05 ) . Paradoxically , DAT athletes across all assessment s reported less athletic competence ( p < .001 ) , less belief authorities were opposed to drug use ( p < .01 ) , and indicated greater risk-taking ( p < .05 ) . At the final assessment , DAT athletes believed less in testing benefits ( p < .05 ) and less that testing was a reason not to use drugs ( p < .01 ) . CONCLUSIONS No DAT deterrent effects were evident for past month use during any of four follow-up periods . Prior-year drug use was reduced in two of four follow-up self-reports , and a combination of drug and alcohol use was reduced at two assessment s as well . Overall , drug testing was accompanied by an increase in some risk factors for future substance use . More research is needed before DAT is considered an effective deterrent for school-based athletes Early onset of substance use among adolescents has been found to be associated with later risky sexual behaviors . This study examined long-term follow-up data from a large r and omized school-based drug prevention trial to ( 1 ) investigate the long-term impact of the prevention program on drug use and sexual behaviors that put one at elevated risk for HIV infection ; and ( 2 ) use growth modeling procedures to examine potential mechanisms of intervention effects . Self-report survey data were collected from students in the 7th grade , prior to the intervention in 1985 , and in grade s 8 , 9 , 10 , and 12 . Participants in the intervention condition received a 30-session drug prevention program in 7th through 9th grade s. Follow-up surveys were completed by 2042 young adults ( mean age = 24 ) in 1998 . As young adults , participants were considered to be engaging in high-risk behavior for HIV infection if they reported having multiple sex partners , having intercourse when drunk or very high , and recent high-risk substance use . The intervention had a direct protective effect on HIV risk behavior in the overall sample in young adulthood . Furthermore , among participants receiving 60 % or more of the prevention program , analyses showed that the intervention significantly reduced growth in alcohol and marijuana intoxication over the course of adolescence , which in turn was associated with a reduction in later HIV risk behavior . The behavioral effects of competence-enhancement drug prevention programs can extend to risk behaviors including those that put one at risk for HIV infection Study objective : The aim of this study was to determine the effect of a multilevel school based intervention on adolescents ’ emotional wellbeing and health risk behaviours . Design : School based cluster r and omised controlled trial . Students were surveyed using laptop computers , twice in the first year of intervention and annually thereafter for a further two years . Setting : Secondary schools . Participants : 2678 year 8 students ( 74 % ) participated in the first wave of data collection . Attrition across the waves was less than 3 % , 8 % , and 10 % respectively with no differential response rate between intervention and control groups at the subsequent waves ( 98 % v 96 % ; 92 % v 92 % , and 90 % v 89 % respectively ) . Main results : A comparatively consistent 3 % to 5 % risk difference was found between intervention and control students for any drinking , any and regular smoking , and friends ’ alcohol and tobacco use across the three waves of follow up . The largest effect was a reduction in the reporting of regular smoking by those in the intervention group ( OR 0.57 , 0.62 , and 0.72 at waves 2 , 3 , and 4 respectively ) . There was no significant effect of the intervention on depressive symptoms , and social and school relationships . Conclusions : While further research is required to determine fully the processes of change , this study shows that a focus on general cognitive skills and positive changes to the social environment of the school can have a substantial impact on important health risk behaviours BACKGROUND Adolescent girls in the United States and around the world are at a heightened risk for sexually transmitted diseases ( STDs ) , including human immunodeficiency virus ( HIV ) . OBJECTIVE To determine the efficacy of a skill-based HIV/STD risk-reduction intervention in reducing self-reported unprotected sexual intercourse among African American and Latino adolescent girls . DESIGN R and omized controlled trial with 3- , 6- , and 12-month follow-ups . SETTING AND PARTICIPANTS Sexually experienced African American and Latino adolescent girls recruited from the adolescent medicine clinic of a children 's hospital serving a low-income inner-city community ( N = 682 , mean age , 15.5 years ) ; 88.6 % were retained at the 12-month follow-up . INTERVENTIONS Three 250-minute interventions based on cognitive-behavioral theories and elicitation research : an information-based HIV/STD intervention provided information necessary to practice safer sex ; a skill-based HIV/STD intervention provided information and taught skills necessary to practice safer sex ; or a health-promotion control intervention concerned with health issues unrelated to sexual behavior . MAIN OUTCOME MEASURES Primary outcome measure was self-reported frequency of unprotected sexual intercourse ; secondary outcomes included the frequency of sexual intercourse while intoxicated , the number of sexual partners , biologically confirmed STDs , and theoretical mediator variables , including the intention to use condoms , beliefs about using condoms , and condom-use knowledge . RESULTS No differences between the information intervention and the health control intervention were statistically significant . Skills-intervention participants ( mean [ SE ] , 2.27 [ 0.81 ] ) reported less unprotected sexual intercourse at the 12-month follow-up than did information-intervention participants ( mean [ SE ] , 4.04 [ 0.80 ] ; P = .03 ) , or health control-intervention participants ( mean [ SE ] , 5.05 [ 0.81 ] ; P = .002 ) . At the 12-month follow-up , skills-intervention participants ( mean [ SE ] , 0.91 [ 0.05 ] ) reported fewer sexual partners ( P = .04 ) compared with health control-intervention participants ( mean [ SE ] , 1.04 [ 0.05 ] ) and were less likely to test positive for STD ( mean [ SE ] , 10.5 % [ 2.9 % ] ) than were health control-intervention participants ( mean [ SE ] , 18.2 % [ 2.8 % ] ; P = .05 ) . No differences in the frequency of unprotected sexual intercourse , the number of partners , or the rate of STD were observed at the 3- or 6-month follow-up between skill-intervention participants and information-intervention or health control-intervention participants . CONCLUSION Skill-based HIV/STD interventions can reduce sexual risk behaviors and STD rate among African American and Latino adolescent girls in clinic setting OBJECTIVES We evaluated the revised Project ALERT drug prevention program across a wide variety of Midwestern schools and communities . METHODS Fifty-five South Dakota middle schools were r and omly assigned to program or control conditions . Treatment group students received 11 lessons in 7th grade and 3 more in 8th grade . Program effects for 4276 8th- grade rs were assessed 18 months after baseline . RESULTS The revised Project ALERT curriculum curbed cigarette and marijuana use initiation , current and regular cigarette use , and alcohol misuse . Reductions ranged from 19 % to 39 % . Program effects were not significant for initial and current drinking or for current and regular marijuana use . CONCLUSIONS School-based drug prevention programs can prevent occasional and more serious drug use , help low- to high-risk adolescents , and be effective in diverse school environments OBJECTIVE To test the effect of prenatal and infancy home visits by nurses on 12-year-old , firstborn children 's use of substances , behavioral adjustment , and academic achievement . DESIGN R and omized controlled trial . SETTING Public system of obstetric and pediatric care in Memphis , Tennessee . PARTICIPANTS We studied 12-year-old , firstborn children ( n = 613 ) of primarily African American , economically disadvantaged women ( 743 r and omized during pregnancy ) . INTERVENTION Program of prenatal and infancy home visits by nurses . OUTCOME MEASURES Use of cigarettes , alcohol , and marijuana ; internalizing , externalizing , and total behavioral problems ; and academic achievement . RESULTS By the time the firstborn child was 12 years of age , those visited by nurses , compared with those in the control group , reported fewer days of having used cigarettes , alcohol , and marijuana during the 30-day period before the 12-year interview ( 0.03 vs 0.18 , P = .02 ) and were less likely to report having internalizing disorders that met the borderline or clinical threshold ( 22.1 % vs 30.9 % , P = .04 ) . Nurse-visited children born to mothers with low psychological re sources , compared with their control group counterparts , scored higher on the Peabody Individual Achievement Tests in reading and math ( 88.78 vs 85.70 , P = .009 ) and , during their first 6 years of education , scored higher on group-administered st and ardized tests of math and reading achievement ( 40.52 vs 34.85 , P = .02 ) . No statistically significant program effects were found on children 's externalizing or total behavioral problems . CONCLUSIONS Through age 12 , the program reduced children 's use of substances and internalizing mental health problems and improved the academic achievement of children born to mothers with low psychological re sources OBJECTIVE Evaluate a community-based tobacco/alcohol use-prevention program group compared with an attention-control condition ( first aid/home safety ) group . METHODS A total of 660 adolescents and 1 adult caregiver for each were recruited through the Migrant Education Program to participate in an 8-week intervention . R and om assignment to the two groups occurred in 22 schools . Seventy 8-week intervention groups ( 37 tobacco/alcohol and 33 attention-control ) were conducted . Assessment s occurred at baseline , immediate post-intervention , and 1- and 2-year follow-ups . Susceptibility to smoking and alcohol as well as smoking and drinking over the past 30 days were the primary outcomes of interest . RESULTS Following intervention , no between-group differences in smoking or drinking were significant . Thirty-day smoking started and remained at very low levels , with the highest group prevalence at any measurement period being 4.7 % and the lowest 2.5 % . Those considered susceptible to smoking dropped by nearly 40 % in the attention-control group and by 50 % in the intervention group from baseline to the final follow-up . ( The overall reduction from post-test to final follow-up was statistically significant . ) Less-acculturated children were less likely to report drinking in the past 30 days . CONCLUSIONS The current intervention was not demonstrated to be effective in preventing cigarette or alcohol consumption . This perhaps is due to very low baseline levels of smoking and drinking in the migrant youth participants UNLABELLED AIMS /INTERVENTION : The Complying with the Minimum Drinking Age project ( CMDA ) is a community trial design ed to test effects of two interventions design ed to reduce alcohol sales to minors : ( 1 ) training for management of retail alcohol establishments and ( 2 ) enforcement checks of alcohol establishments . DESIGN CMDA is a multi-community time-series quasi-experimental trial with a nested cohort design . SETTING / PARTICIPANTS CMDA was implemented in 20 cities in four geographic areas in the US Midwest . MEASUREMENTS The core outcome , propensity for alcohol sales to minors , was directly tested with research staff who attempted to purchase alcohol without showing age identification using a st and ardized protocol in 602 on-premise and 340 off-premise alcohol establishments . Data were collected every other week in all communities over 4 years . Mixed-model regression and Box-Jenkins time-series analyses were used to assess short- and long-term establishment-specific and general community-level effects of the two interventions . FINDINGS Effects of the training intervention were mixed . Specific deterrent effects were observed for enforcement checks , with an immediate 17 % reduction in likelihood of sales to minors . These effects decayed entirely within 3 months in off-premise establishments and to an 8.2 % reduction in on-premise establishments . CONCLUSIONS Enforcement checks prevent alcohol sales to minors . At the intensity levels tested , enforcement primarily affected specific establishments checked , with limited diffusion to the whole community . Finally , most of the enforcement effect decayed within 3 months , suggesting that a regular schedule of enforcement is necessary to maintain deterrence Four years of longitudinal data from 373 families participating in a r and omized intervention-control clinical trial were used to examine whether intervention effects on adolescent alcohol and tobacco use trajectories were moderated by family risk , as defined by parental social emotional maladjustment . Consistent with earlier outcome evaluations based on analyses of covariance , analyses confirmed that both the Preparing for the Drug Free Years program and the Iowa Strengthening Families Program favorably influenced alcohol use index trajectories across the time frame of the study ; only the latter program , however , evidence d positive effects on a tobacco use index . Concerning the primary research question , analyses provided no support for family risk moderation of any intervention effect . Findings indicate the feasibility of developing universal preventive interventions that offer comparable benefits to all families This study examined mediators of the Strong African American Families Program , a r and omized , dual-focus prevention trial intended to delay the onset of alcohol use and reduce alcohol consumption among rural African American youths . More specifically , it demonstrated that changes in consumption 2 yrs after the intervention were mediated through 2 different paths , a social reaction path and a reasoned/intention path . The social reaction path provided evidence that relative to the control condition , the intervention decreased children 's willingness to drink by making their images of drinkers less favorable . The reasoned/intention path provided evidence that the intervention influenced the children 's intentions to drink by increasing targeted parenting behaviors related to alcohol . Furthermore , the data demonstrate that these changes in willingness and intentions were independently associated with alcohol consumption at the follow-up , and they suggest that a dual-process model approach that targets both intentions and willingness can be more successful than either approach alone This article examines the effectiveness of a career-oriented intervention for preventing involvement with alcohol , tobacco , and other drugs ( ATODs ) and violence and for promoting resilient behavior among eighth- grade , African American middle school students ( N=178 ; n=92 intervention and n=86 comparison ) through the implementation of the Building Resiliency and Vocational Excellence ( BRAVE ) Program . Students were r and omly assigned to either the intervention or control group . Students in the evaluation participated in the school-based BRAVE Program intervention and the st and ard public school curriculum . Comparison students participated only in the st and ard curriculum . Alcohol , tobacco , and other drug use and violent behavior were assessed for 178 students at baseline , post-test , and one-year follow up ( one year after baseline ) . Results revealed a beneficial effect of the intervention on participants ’ frequency of use of alcohol ( p<.04 ) and marijuana ( p<.05 ) , but no effect for violent behavior The aim of this study was to identify whether a brief motivational interviewing and cognitive-behavioural-based alcohol intervention group ( AIG ) programme is feasible with young people at risk of developing a problem with alcohol , and to assess the short-term effectiveness of the intervention . Participants were assigned r and omly to receive a group intervention of four sessions duration ( n=17 ; AIG ) or no treatment ( n=17 , control group ) . Participants were volunteers recruited from a youth centre on the Central Coast of New South Wales , Australia , comprising youths aged 12 - 19 years who were interested in participating in the study . The Readiness to Change Question naire , items from the AUDIT , the DAP Quick Screen and a knowledge question naire were administered at pretreatment , post-treatment and at 1- and 2-month follow-ups . Participants in the AIG programme showed an increase in readiness to reduce their alcohol consumption . They also reduced their frequency of drinking at post-treatment and the first follow-up assessment , while the control group reported increases at the second follow-up assessment . The control group also increased their hazardous drinking and frequency of binge drinking compared to the AIG . The intervention appeared to improve the AIG participants ' knowledge about alcohol and its effects . The results provide preliminary evidence for the effectiveness of the AIG programme in training young people to set limits on alcohol consumption , increase awareness of safe drinking levels and the effects of alcohol abuse . This pilot study also showed that young people who are identified as being ' at risk ' of developing alcohol abuse , and who are also ambivalent about changing drinking behaviours , can be recruited and retained in a treatment programme PURPOSE The Strong African American Families program , a universal intervention to deter alcohol use among rural African American preadolescents , was evaluated to determine whether it also prevented conduct problems across the 29 months separating the pretest and long-term follow-up assessment s. The program is based on a context ual model in which intervention effects on parental behavior and youth protective factors are hypothesized to lead to behavior changes . METHODS African American 11-year-olds ( N = 667 ) and their primary caregivers were r and omly selected from public school lists of fifth- grade students and r and omly assigned to an intervention ( n = 369 ) or control ( n = 298 ) condition . Intervention families participated in a 7-week family skills training program design ed to deter alcohol use . Each meeting included separate , concurrent sessions for parents and children , followed by a joint parent-child session during which the families practice d the skills they learned in their separate sessions . Control families were mailed leaflets regarding early adolescent development , stress management , and exercise . All families completed in-home pretest , posttest , and long-term follow-up interviews during which parent-report and self-report data regarding conduct problems , low self-control , deviance-prone peer affiliations , parenting , and youth protective processes were gathered . RESULTS Intent-to-treat analyses indicated that prevention-group youth were less involved than control-group youth in conduct problems across time . As hypothesized , prevention effects were stronger for youth at greater risk of developing conduct problems . Intervention targeted parenting and youth factors partially accounted for intervention effects among high risk youth . CONCLUSIONS Although the Strong African American Families program was design ed to deter underage drinking , it is also effective in preventing the development of conduct problems BACKGROUND This article reports the results of a 5-year , longitudinal evaluation of the effectiveness of Drug Abuse Resistance Education ( DARE ) , a school-based primary drug prevention curriculum design ed for introduction during the last year of elementary education . DARE is the most widely disseminated school-based prevention curriculum in the United States . METHOD Twenty-three elementary schools were r and omly assigned to receive DARE and 8 were design ated comparison schools . Students in the DARE schools received 16 weeks of protocol -driven instruction and students in the comparison schools received a drug education unit as part of the health curriculum . All students were pretested during the 6th grade prior to delivery of the programs , posttested shortly after completion , and resurveyed each subsequent year through the 10th grade . Three-stage mixed effects regression models were used to analyze these data . RESULTS No significant differences were observed between intervention and comparison schools with respect to cigarette , alcohol , or marijuana use during the 7th grade , approximately 1 year after completion of the program , or over the full 5-year measurement interval . Significant intervention effects in the hypothesized direction were observed during the 7th grade for measures of students ' general and specific attitudes toward drugs , the capability to resist peer pressure , and estimated level of drug use by peers . Over the full measurement interval , however , average trajectories of change for these outcomes were similar in the intervention and comparison conditions . CONCLUSIONS The findings of this 5-year prospect i ve study are largely consonant with the results obtained from prior short-term evaluations of the DARE curriculum , which have reported limited effects of the program upon drug use , greater efficacy with respect to attitudes , social skills , and knowledge , but a general tendency for curriculum effects to decay over time . The results of this study underscore the need for more robust prevention programming targeted specifically at risk factors , the inclusion of booster sessions to sustain positive effects , and greater attention to interrelationships between developmental processes in adolescent substance use , individual level characteristics , and social context OBJECTIVE To prevent early adolescent health risk behaviors and to maintain or improve safety behaviors , we compared the effects of 2 interventions , delivered through pediatric primary care practice s. The interventions , based on an office systems ' approach , sought to prevent early drinking and smoking or to influence bicycle helmet use , gun storage , and seatbelt safety for children who were followed from fifth/sixth grade s through eighth/ninth grade s. DESIGN Setting s and Participants . Twelve pediatric practice s in New Engl and were paired according to practice size and assigned r and omly within pairs to deliver the multicomponent interventions , which built on pediatric primary care clinicians performing as counselors and role models during health supervision visits and other office encounters . INTERVENTION One intervention arm focused on alcohol and tobacco use . The other intervention arm focused on gun safety , bicycle helmet , and seatbelt use . Office systems provided infrastructure that supported the clinician 's role . Clinician messages encouraged family communication and rule setting about the issues of the middle school years . The intervention was initiated during a health supervision visit and continued for 36 months . Both child and parent received quarterly newsletters to reinforce the clinician messages . OUTCOME MEASURES The primary outcomes were ever drinking alcohol , ever smoking , ever using smokeless tobacco , using a bicycle helmet in the previous year , using a seatbelt in the previous 30 days , and guns in the child 's home in locked storage . RESULTS The pediatric practice s recruited 85 % ( N = 3525 ) of the practice s ' fifth/sixth grade children and their responding parents . We obtained 36 months ' follow-up data on 2183 child-parent pairs . Chart audit verified that the intervention was implemented . Additional data from interviews and surveys showed that parents , children , and pediatric clinicians found the intervention useful . Despite this , comparisons between the 2 study arms show no significant intervention effects in the prevention of alcohol and tobacco use or gun storage or seatbelt safety . There was a negative effect in the alcohol arm . Only bicycle helmet use showed a positive outcome . CONCLUSION With rigorous evaluation , 2 office interventions failed to produce desired outcomes . Coordinated multiple setting s for prevention interventions are probably necessary OBJECTIVE This study evaluated a gender-specific , computer-mediated intervention program to prevent underage drinking among early adolescent girls . METHOD Study participants were adolescent girls and their mothers from New York , New Jersey , and Connecticut . Participants completed pretests online and were r and omly divided between intervention and control arms . Intervention-arm girls and their mothers interacted with a computer program aim ed to enhance mother-daughter relationships and to teach girls skills for managing conflict , resisting media influences , refusing alcohol and drugs , and correcting peer norms about underage drinking , smoking , and drug use . After intervention , all participants ( control and intervention ) completed posttest and follow-up measurements . RESULTS Two months following program delivery and relative to control-arm participants , intervention-arm girls and mothers had improved their mother-daughter communication skills and their perceptions and applications of parental monitoring and rule- setting relative to girls ' alcohol use . Also at follow-up , intervention-arm girls had improved their conflict management and alcohol use-refusal skills ; reported healthier normative beliefs about underage drinking ; demonstrated greater self-efficacy about their ability to avoid underage drinking ; reported less alcohol consumption in the past 7 days , 30 days , and year ; and expressed lower intentions to drink as adults . CONCLUSIONS Study findings modestly support the viability of a mother-daughter , computer-mediated program to prevent underage drinking among adolescent girls . The data have implication s for the further development of gender-specific approaches to combat increases in alcohol and other substance use among American girls OBJECTIVE This study tested a CD-ROM intervention with and without a parent involvement component to reduce risk of alcohol use among an urban sample of early adolescents . METHOD Youths ( N = 514 , mean age 11.5 years at recruitment ) were assigned r and omly by community site to receive the CD-ROM intervention , the CD-ROM plus parent intervention , or no intervention . All youths completed pretest , posttest and three annual follow-up measurements . After pretesting , youths and parents received their respective interventions . RESULTS Main effects of the intervention and for measurement occasion as well as interaction effects of the intervention by measurement occasion were seen for substance use and related outcomes . Over time , youths in all 3 groups reported increased use of alcohol , tobacco and marijuana ; youths who received the interventions reported smaller increases than control youths . At 3-year follow-up , alcohol use was lower for CD-ROM plus parent intervention youths than for CD-ROM only youths , who , in turn , reported less use than controls . Cigarette use was lower for youths in either intervention group than in the control group at posttest and at 1- , 2- and 3-year follow-ups . Marijuana use was lower for youths in either intervention than for controls at 1- , 2- and 3-year follow-ups . Youths in both intervention groups outperformed control youths at posttest and at 1- and 3-year follow-ups on levels of negative and peer influence toward substance use . Finally , at the 3-year follow-up , youths in the CD-ROM plus parent intervention group reported more family involvement in their alcohol use prevention efforts than did youths in the CD-ROM group , who , in turn , reported more positive levels of family involvement than youths in the control group . CONCLUSIONS Study findings modestly support the CD-ROM intervention with and without the parent intervention to reduce alcohol use risks among urban early adolescents OBJECTIVE To evaluate the long-term efficacy of a school-based approach to drug abuse prevention . DESIGN R and omized trial involving 56 public schools that received the prevention program with annual provider training workshops and ongoing consultation , the prevention program with videotaped training and no consultation , or " treatment as usual " ( ie , controls ) . Follow-up data were collected 6 years after baseline using school , telephone , and mailed surveys . PARTICIPANTS A total of 3597 predominantly white , 12th- grade students who represented 60.41 % of the initial seventh- grade sample . INTERVENTION Consisted of 15 classes in seventh grade , 10 booster sessions in eighth grade , and five booster sessions in ninth grade , and taught general " life skills " and skills for resisting social influences to use drugs . MEASURES Six tobacco , alcohol , and marijuana use self-report scales were recorded to create nine dichotomous drug use outcome variables and eight polydrug use variables . RESULTS Significant reductions in both drug and polydrug use were found for the two groups that received the prevention program relative to controls . The strongest effects were produced for individuals who received a reasonably complete version of the intervention -- there were up to 44 % fewer drug users and 66 % fewer polydrug ( tobacco , alcohol , and marijuana ) users . CONCLUSIONS Drug abuse prevention programs conducted during junior high school can produce meaningful and durable reductions in tobacco , alcohol , and marijuana use if they ( 1 ) teach a combination of social resistance skills and general life skills , ( 2 ) are properly implemented , and ( 3 ) include at least 2 years of booster sessions Prior investigations have linked behavioral competencies in primary school to a reduced risk of later drug involvement . In this r and omized prevention trial , we sought to quantify the potential early impact of two developmentally inspired universal preventive interventions on the risk of early-onset alcohol , inhalant , tobacco , and illegal drug use through early adolescence . Participants were recruited as they entered first grade within nine schools of an urban public school system . Approximately , 80 % of the sample was followed from first to eighth grade s. Two theory-based preventive interventions , ( 1 ) a family-school partnership ( FSP ) intervention and ( 2 ) a classroom-centered ( CC ) intervention , were developed to improve early risk behaviors in primary school . Generalized estimating equations ( GEE ) multivariate response profile regressions were used to estimate the relative profiles of drug involvement for intervention youths versus controls , i.e. youth in the st and ard educational setting . Relative to control youths , intervention youths were less likely to use tobacco , with modestly stronger evidence of protection associated with the CC intervention ( RR=0.5 ; P=0.008 ) as compared to protection associated with the FSP intervention ( RR=0.6 ; P=0.042 ) . Intervention status was not associated with risk of starting alcohol , inhalants , or marijuana use , but assignment to the CC intervention was associated with reduced risk of starting to use other illegal drugs by early adolescence , i.e. heroin , crack , and cocaine powder ( RR=0.32 , P=0.042 ) . This study adds new evidence on intervention-associated reduced risk of starting illegal drug use . In the context of ' gateway ' models , the null evidence on marijuana is intriguing and merits attention in future investigations CONTEXT Compared with their peers with nondivorced parents , adolescents with divorced parents are more likely to have mental health problems , drop out of school , and become pregnant . The long-term effects of intervention programs for this population are unknown . OBJECTIVE To evaluate the long-term effectiveness of 2 programs design ed to prevent mental health problems in children with divorced parents . DESIGN AND SETTING Six-year follow-up of a r and omized controlled trial of 2 intervention programs ( mother program : 11 group and 2 individual sessions ; mother plus child program : mother program and 11 group sessions for children ) and a control condition ( books on postdivorce adjustment ) , which was conducted in a large metropolitan US city from April 1998 through March 2000 . PARTICIPANTS A total of 218 families ( 91 % of the original sample ) with adolescents aged between 15 and 19 years were reinterviewed . MAIN OUTCOME MEASURES Externalizing and internalizing problems , diagnosed mental disorders , drug and alcohol use , and number of sexual partners . RESULTS Eleven percent of adolescents in the mother plus child program ( 95 % confidence interval [ CI ] , 3.8%-18.2 % ) had a 1-year prevalence of diagnosed mental disorder compared with 23.5 % ( 95 % CI , 13.8%-33.2 % ) of adolescents in the control program ( P = .007 ) . Adolescents in the mother plus child program had fewer sexual partners ( mean [ SE ] , 0.68 [ 0.16 ] ) compared with adolescents in the control program ( 1.65 [ 0.37 ] ; P = .01 ) . Adolescents with higher initial mental health problems whose families were in the mother plus child program had lower externalizing problems ( P = .007 ) and fewer symptoms of mental disorder ( P = .02 ) compared with those in the control program . Compared with controls , adolescents whose mothers participated in the mother program and who had higher initial mental health problems had lower levels of externalizing problems ( P<.001 ) ; fewer symptoms of mental disorder ( P = .005 ) ; and less alcohol ( P = .005 ) , marijuana ( P = .02 ) , and other drug use ( P = .01 ) . CONCLUSIONS In adolescents of divorced parents , the mother program and the mother plus child program reduced symptoms of mental disorder ; rates of diagnoses of mental disorder ; levels of externalizing problems ; marijuana , alcohol , and other drug use ; and number of sexual partners R and omized field trials provide unique opportunities to examine the effectiveness of an intervention in real world setting s and to test and extend both theory of etiology and theory of intervention . These trials are design ed not only to test for overall intervention impact but also to examine how impact varies as a function of individual level characteristics , context , and across time . Examination of such variation in impact requires analytical methods that take into account the trial 's multiple nested structure and the evolving changes in outcomes over time . The models that we describe here merge multilevel modeling with growth modeling , allowing for variation in impact to be represented through discrete mixtures -- growth mixture models-- and nonparametric smooth functions -- generalized additive mixed models . These methods are part of an emerging class of multilevel growth mixture models , and we illustrate these with models that examine overall impact and variation in impact . In this paper , we define intent-to-treat analyses in group-r and omized multilevel field trials and discuss appropriate ways to identify , examine , and test for variation in impact without inflating the Type I error rate . We describe how to make causal inferences more robust to misspecification of covariates in such analyses and how to summarize and present these interactive intervention effects clearly . Practical strategies for reducing model complexity , checking model fit , and h and ling missing data are discussed using six r and omized field trials to show how these methods may be used across trials r and omized at different levels BACKGROUND The empirical evidence of effectiveness of many school-based programs against substance abuse is rather weak . The EU-Dap study is a multicenter cluster r and omized community trial ( C RCT ) design ed to evaluate such a program . This paper presents study design and baseline characteristics of the study population . METHODS 170 schools from 9 centers from seven countries ( Austria , Belgium , Germany , Greece , Italy , Spain , Sweden ) , stratified according to average social status in the catchment area , were r and omized to either three variants of the active intervention ( basic curriculum , basic with peer involvement , and basic with parent involvement ) or to a control group . The program under evaluation is based on a comprehensive social influence approach , and was delivered during the scholar year 2004 - 2005 to a population of 12- to 14-year-old students attending junior high school . An anonymous question naire administered before and after the intervention was used to track behavioral and attitudinal changes . RESULTS All in all , we included in the study 143 schools and 7079 students , of which 3547 in the intervention groups and 3532 in the control group . At baseline , 34.9 % of students had smoked cigarettes , 24.7 % had been drunk , and 8.9 % had used cannabis at least once in life . DISCUSSION EU-Dap is the first European multicenter r and omized study to evaluate the effectiveness of a school program targeting tobacco , alcohol and drug use . The baseline assessment showed high prevalence and wide geographical variations of substance use OBJECTIVE To evaluate the effectiveness of the school-based drug abuse prevention program developed in the EU-Dap study ( EUropean Drug Abuse Prevention trial ) in preventing the use of tobacco , alcohol and drugs at the post-test . METHODS Cluster R and omised Controlled Trial . Seven European countries participated in the study ; 170 schools ( 7079 pupils 12 - 14 years of age ) were r and omly assigned to one of three experimental conditions or to a control condition during the school year 2004/2005 . A pre-test survey assessing past and current substance use was conducted before the implementation of the program . The program consisted in 12-hour class-based curriculum based on a comprehensive social-influence approach . A post-test survey was carried out in all participating schools , 3 months after the end of the program . The association between program condition and change in substance use at post-test was expressed as adjusted Prevalence Odds Ratio ( POR ) , estimated by multilevel regression model . RESULTS Program effects were found for daily cigarette smoking ( POR=0.70 ; 0.52 - 0.94 ) and episodes of drunkenness in the past 30 days ( POR=0.72 ; 0.58 - 0.90 for at least one episode , POR=0.69 ; 0.48 - 0.99 for three or more episodes ) , while effects on Cannabis use in the past 30 days were of marginal statistical significance ( POR=0.77 ; 0.60 - 1.00 ) . The curriculum was successful in preventing baseline non-smokers or sporadic smokers from moving onto daily smoking , but it was not effective in helping baseline daily smokers to reduce or stop smoking . CONCLUSION School curricula based on a comprehensive social-influence model may delay progression to daily smoking and episodes of drunkenness OBJECTIVE This article summarizes the literature on alcohol initiation outcomes of universal family interventions and examines the long-term effects of the Iowa Strengthening Families Program ( ISFP ) on these outcomes . METHOD A longitudinal , controlled efficacy study of the ISFP was conducted with 446 families from 22 rural school districts in a Midwestern state . Alcohol initiation behaviors were measured by a four-item index ( Alcohol Initiation Index [ AII ] ) , with low scores representing a lower level of alcohol initiation . The AII was examined using mixed-model analyses of covariance . Relative reduction rates for individual initiation behaviors and initiation differences among higher- and lower-dosage intervention groups were calculated . RESULTS AII scores were significantly lower among intervention group adolescents than among control group adolescents at 1- and 2-year follow-up assessment s. Relative-reduction rate differences between intervention and control groups on specific alcohol initiation behaviors ( e.g. , onset of drinking without parental permission , onset of drunkenness ) ranged from approximately 30 % to 60 % . Dosage-related initiation differences were evident only at the 1-year follow-up . CONCLUSIONS Studies indicating the public health benefits of universal interventions that delay the initiation of alcohol use also underscore the importance of the current line of investigation . All effect sizes and relative reduction rates of specific alcohol initiation behaviors suggest the practical significance of the findings . The gap in the prevention outcome knowledge base in this area of investigation could be filled with more rigorous universal family-focused intervention studies that address a wide range of implementation and method ological issues OBJECTIVE The aim of this study was to investigate the effectiveness of a brief intervention for m and ated students in the context of the University Assistance Program , a Student Assistance Program developed and modeled after workplace Employee Assistance Programs . METHOD Participants were 265 ( 196 males and 69 females ) judicially m and ated college students enrolled in a large , urban university in the northeast United States . All participants were sanctioned by the university 's judicial office for an alcohol- or drug-related violation . Participants were r and omized to one of two intervention conditions ( the University Assistance Program or services as usual ) and were assessed at baseline and 3 and 6 months after intervention . RESULTS Growth curve analyses showed that , relative to services as usual , the University Assistance Program was more efficacious in reducing past-90-day weekday alcohol consumption and the number of alcohol-related consequences while increasing past-90-day use of protective behaviors and coping skills . No significant differences in growth trajectories were found between the two intervention conditions on past-90-day blood alcohol concentration , total alcohol consumption , or weekend consumption . CONCLUSIONS The University Assistance Program may have a possible advantage over services as usual for m and ated students Reducing the prevalence of adolescent cigarette smoking and alcohol drinking are public health goals of the United States . Although families have strong influence on their children , few r and omized studies have examined whether family-directed programs influence those behaviors in general universal population s. This paper reports findings from an evaluation of a family program that features the mailing of four booklets to adult family members with follow-up telephone calls by health educators . A national sample of adolescent – parent pairs and a r and omized experimental design were used to evaluate the program . Baseline users and nonusers of those substances were considered simultaneously in analyses so that program influences on smoking and drinking prevalence could be examined . The findings suggest that the program significantly reduced the prevalence of smoking cigarettes and drinking alcohol among adolescents . These findings are discussed in the context of earlier reports of research on the family program and implication s for public health This study developed and tested skills- and community-based approaches to prevent substance abuse among Native American youth . After completing pretest measurements , 1,396 third- through fifth- grade Native American students from 27 elementary schools in five states were divided r and omly by school into two intervention arms and one control arm . Following intervention delivery , youths in all arms completed posttest measurements and three annual follow-up measurements . Youths in schools assigned to the intervention arms learned cognitive and behavioral skills for substance abuse prevention . One intervention arm additionally engaged local community residents in efforts to prevent substance use among Native American youth . Outcome assessment batteries measured youths ' reported use of smoked and smokeless tobacco , alcohol , and marijuana . Over the course of the 3.5-year study , increased rates of tobacco , alcohol , and marijuana use were reported by youths across the three arms of the study . Though cigarette use was unaffected by intervention , follow up rates of smokeless tobacco , alcohol , and marijuana use were lower for youths who received skills intervention than for youths in the control arm . Community intervention components appeared to exert no added beneficial influence on youths ' substance use , beyond the impact of skills intervention components alone . Finally , gender differences were apparent across substances , measurements , and study arms , with girls smoking more cigarettes and boys using more smokeless tobacco , alcohol , and marijuana OBJECTIVES This paper describes the one-year outcomes of the fourth experimental trial of Project Towards No Drug Abuse . Two theoretical content components of the program were examined to increase our underst and ing of the relative contribution of each to the effectiveness of the program . METHODS High schools in Southern California ( n=18 ) were r and omly assigned to one of three conditions : cognitive perception information curriculum , cognitive perception information+behavioral skills curriculum , or st and ard care ( control ) . The curricula were delivered to high school students ( n=2734 ) by project health educators and regular classroom teachers . Program effectiveness was assessed with both dichotomous and continuous measures of 30-day substance use at baseline and one-year follow-up . RESULTS Across all program schools , the two different curricula failed to significantly reduce dichotomous measures of substance use ( cigarette , alcohol , marijuana , and hard drugs ) at one-year follow-up . Both curricula exerted an effect only on the continuous measure of hard drug use , indicating a 42 % ( p=0.02 ) reduction in the number of times hard drugs were used in the last 30 days in the program groups relative to the control . CONCLUSIONS The lack of main effects of the program on dichotomous outcomes was contrary to previous studies . An effect on an ordinal count measure of hard drug use among both intervention conditions replicates previous work and suggests that this program effect may have been due to changes in cognitive misperception of drug use rather than behavioral skill This study assessed the impact of school-based social competence training on skills , social adjustment , and self-reported substance use of 282 sixth and seventh grade rs . Training emphasized broad-based competence promotion in conjunction with domain-specific application to substance abuse prevention . The 20-session program comprised six units : stress management , self-esteem , problem solving , substances and health information , assertiveness , and social networks . Findings indicated positive training effects on Ss ' skills in h and ling interpersonal problems and coping with anxiety . Teacher ratings revealed improvements in Ss ' constructive conflict resolution with peers , impulse control , and popularity . Self-report ratings indicated gains in problem-solving efficacy . Results suggest some preventive impact on self-reported substance use intentions and excessive alcohol use . In general , the program was found to be beneficial for both inner-city and suburban students The purpose of this study was to describe aspects of the first alcohol-use experience , and examine the predictive relations among age of first use , context of alcohol use initiation , and problem drinking with and without controls for psychosocial risk factors . Data were from the Rutgers Health and Human Development Project , a five-wave , prospect i ve study of substance-use behaviors in a community sample . Respondents , who were first interviewed at age 12 ( 1979–81 ) and most recently at age 30 or 31 ( 1999–2000 ) ( N = 371 ) , reported on their first drinking experience , and on a range of known risk factors for alcohol abuse . Most alcohol initiation occurred during a family gathering . Regardless of initiation context , youth who drank at an early age were more likely than youth who initiated later to become problem drinkers , although the risk was relatively greater for the youth who first drank outside a family gathering . Based on multivariate logistic regressions , feeling drunk at initiation was the only onset-related variable significantly associated with problem drinking ; other significant risks factors included male gender , delinquency , and family history of alcoholism . Because most initiation occurs at a family gathering , alcoholism prevention research may benefit from examining the role that drinking in family context s could play with regard to socializing young drinkers to less risky drinking behaviors in adulthood . In particular , further research focusing on the subjective effects experienced by youth when they first drink may be merited This study extends earlier investigation of family risk-related moderation of two brief , family-focused preventive interventions . It examines effects on the trajectories of substance initiation over a period of six years after a pretest assessment , evaluating whether effects were comparable across higher- and lower-risk subgroups . The two interventions , design ed for general- population families of adolescents , were the seven-session Iowa Strengthening Families Program ( ISFP ) and the five-session Preparing for the Drug Free Years program ( PDFY ) . Thirty-three rural public schools were r and omly assigned to either the ISFP , the PDFY , or a minimal contact control condition . Curvilinear growth curve analyses were used to evaluate the universality of intervention effectiveness by testing for risk moderation of intervention effects on school-level substance use trajectories of initiation of alcohol and illicit substance use . Results were most consistent with the interpretation that both interventions provided comparable benefits for both outcome measures , regardless of family risk status . Findings are discussed in terms of their implication s for implementing universal preventive interventions in general population OBJECTIVES The purpose of the study was to determine whether a universal school-based substance abuse prevention program , Take Charge of Your Life ( TCYL ) , prevents or reduces the use of tobacco , alcohol , or marijuana . METHODS Eighty-three school clusters ( representing school districts ) from six metropolitan areas were r and omized to treatment ( 41 ) or control ( 42 ) conditions . Using active consenting procedures , 19,529 seventh grade rs were enrolled in the 5-year study . Self-administered surveys were completed by the students annually . Trained Drug Abuse Resistance Education ( D.A.R.E. ) police officers presented TCYL in seventh and ninth grade s in treatment schools . Analyses were conducted with data from 17,320 students who completed a baseline survey . Intervention outcomes were measured using self-reported past-month and past-year use of tobacco , alcohol , and marijuana when students were in the 11th grade . RESULTS Main effect analyses show a negative program effect for use of alcohol and cigarettes and no effect for marijuana use . Subgroup analyses indicated that the negative effect occurred among nonusers at baseline , and mostly among white students of both genders . A positive program effect was found for students who used marijuana at baseline . Two complementary papers explore the relationship of the targeted program mediators to the use of alcohol , tobacco , and marijuana and specifically for students who were substance-free or who used substances at baseline . CONCLUSIONS The negative impact of the program on baseline nonusers of alcohol and tobacco indicate that TCYL should not be delivered as a universal prevention intervention . The finding of a beneficial effect for baseline marijuana users further supports this conclusion . The programmatic and method ological challenges faced by the Adolescent Substance Abuse Prevention Study ( ASAPS ) and lessons learned offer insights for prevention research ers who will be design ing similar r and omized field trials in the future OBJECTIVE The potential effectiveness of two group-administered social-skills training interventions for reducing high-risk drinking behavior was evaluated through a prospect i ve r and omized intervention trial with 3,406 members of a national college fraternity . METHOD Ninety eight of 99 chapters of a national fraternity were r and omly assigned , within three strata , to receive ( 1 ) a 3-hour baseline intervention , ( 2 ) the same baseline intervention plus two booster sessions , or ( 3 ) assessment s only . The current article emphasizes a rigorous intent-to-treat analysis model that compares outcomes among members assigned to receive study interventions ( vs assessment -only sites ) regardless of whether they actually did receive them ; it also includes individuals at intervention sites even if they did not participate . This model allows us to address a social policy issue regarding the effect that introducing such an intervention may have in changing the high-risk normative drinking environment of the fraternity itself . RESULTS Frequent heavy drinkers ( 64.2 % of members ) assigned to either intervention showed significant reductions at a 6-month follow-up in their frequency of drinking , heavy drinking , and drinking to intoxication ; plus , they reported consuming fewer drinks overall . At 12 and 18 months postbaseline , these positive outcomes had largely dissipated . Additionally , there was an increase in drinking among lower-risk members 18 months postbaseline , which may be the result of factors other than differential attrition . CONCLUSIONS Findings suggest that introducing such a brief intervention can effectively reduce risky drinking behavior on a short-term basis in high-risk members of a national fraternity . Future studies may wish to focus on strategies for sustaining positive outcomes for longer , plus would benefit , in general , from learning more about mechanisms of change AIMS Hazardous alcohol use is a leading cause of death among adolescents and young adults world-wide , yet few effective prevention interventions exist . This study was the first to examine a computerized harm minimization intervention to reduce alcohol misuse and related harms in adolescents . DESIGN Cluster r and omized controlled trial of a six-session curriculum-integrated harm minimization prevention program . The intervention was delivered by computer in the form of a teenage drama , which provided education through alcohol-related scenarios to which young people could relate . SETTING Schools in Australia . PARTICIPANTS A total of 1466 year 8 students ( 13 years ) from 16 high schools in Australia were allocated r and omly to a computerized prevention program ( n = 611 , eight schools ) or usual classes ( n = 855 , eight schools ) . MEASUREMENTS Change in knowledge , alcohol use , alcohol-related harms and alcohol expectancies . FINDINGS A computerized prevention program was more effective than usual classes in increasing alcohol-related knowledge of facts that would inform safer drinking choices and decreasing the positive social expectations which students believed alcohol may afford . For females it was effective in decreasing average alcohol consumption , alcohol-related harms and the frequency of drinking to excess ( more than four st and ard drinks ; 10 g ethanol ) . For males the behavioural effects were not significant . CONCLUSIONS A harm minimization approach is effective in educating young people about alcohol-related risks and is effective in reducing risky drinking and harms among girls . Reduction of problems among boys remains a challenge OBJECTIVE To evaluate the effects of Project ALERT on adolescents ' lifetime and 30-day use of cigarettes , alcohol , marijuana , and inhalants . DESIGN Cluster r and omized trial . SETTING Schools from 11 states were enrolled in 2 successive cohorts from 2004 to 2008 . PARTICIPANTS All public schools in the United States that included grade s 6 through 8 and enrolled at least 100 students in sixth grade were recruited . Of the 40 schools that began the study , 34 ( 17 per condition ) completed it . Data were analyzed from 5883 unique participants . Intervention Project ALERT , a manualized classroom-based substance use prevention curriculum for the middle grade s , was taught to sixth and seventh grade rs . MAIN OUTCOME MEASURES Students were surveyed before the onset of the intervention , as sixth grade rs , and after the completion of the 2-year intervention , as seventh grade rs . Outcome measures included lifetime and 30-day use of cigarettes , alcohol , marijuana , and inhalants . RESULTS At baseline , students in the intervention condition were slightly to moderately more likely to report use for each of the 8 measures examined than were students in the control condition . For all measures except lifetime use of cigarettes , these differences were less pronounced at follow-up and therefore were in the direction of favorable program effects . These changes were statistically significant , however , for only 1 outcome measure , past 30-day use of alcohol ( reduction in the adjusted odds ratio from 2.07 at baseline to 1.32 at follow-up ; P = .006 ) . CONCLUSION Project ALERT was not effective when delivered to the sixth grade population we targeted The Lifestyle Management Class ( LMC ) was evaluated as a universal and targeted alcohol prevention program among voluntary and m and ated college students . The relative efficacy of peer- and professional-led group interventions was also tested in this r and omized , controlled design . LMC participants showed decreases in driving after drinking relative to control participants . Changes in heavy drinking varied as a function of treatment condition , readiness to change , and gender , with a trend toward larger decreases among voluntary LMC participants high in readiness to change and a comparable though nonsignificant advantage for male LMC participants in the m and ated sample . The LMC was comparably effective for m and ated and voluntary students , with no clear advantage for peer- or professional-led groups OBJECTIVE Systematic evaluation of theoretically and empirically based family programs to prevent adolescent alcohol use/misuse is limited . Data presented here are from a longitudinal study evaluating a home-based universal adolescent alcohol use prevention program . The intervention was design ed to enhance protective factors and minimize risk factors identified as influencing adolescent alcohol use . METHOD A r and omized pretest/posttest repeated measures design was used . Adolescents ( N = 428 ; 54 % females , 86 % European American ) and their parents were recruited from three Midwestern school districts . Families were r and omly assigned to either a three-session family intervention or a no-intervention control condition . Pretest data collection and the intervention occurred when the adolescents were in fourth grade , and a booster intervention was given in seventh grade . Posttest data collection was completed each year for 4 years in the classroom for adolescents . RESULTS The intervention was associated with a reduction in alcohol use ( F = 5.16 , 4/421 df , p < .001 ) and misuse ( F = 3.08 , 4/421 df , p < .05 ) for those adolescents in the intervention condition who were not using alcohol prior to the initiation of the program , but not for those who were using alcohol before initiation of the program . CONCLUSIONS The results support the possible effectiveness of the family intervention as a universal prevention program for decreasing initiation of alcohol use and subsequent misuse for the majority of adolescents who do not report prior drinking . However , additional intervention approaches appear necessary for adolescents who have already used alcohol This study reports on the impact of a “ drink driving education program ” taught to grade ten high school students . The program which involves twelve lessons uses strategies based on the Ajzen and Madden theory of planned behavior . Students were trained to use alternatives to drink driving and passenger behaviors . One thous and seven hundred and seventy-four students who had been taught the program in r and omly assigned control and intervention schools were followed up three years later . There had been a major reduction in drink driving behaviors in both intervention and control students . In addition to this cohort change there was a trend toward reduced drink driving in the intervention group and a significant reduction in passenger behavior in this group . Readiness to use alternatives suggested that the major impact of the program was on students who were experimenting with the behavior at the time the program was taught . The program seems to have optimized concurrent social attitude and behavior change The current study describes the extensive cross-cultural adaptation of a brief home-based alcohol prevention program for racially and ethnically diverse sixth grade students and their families , using a r and omized controlled trial design involving 60 public schools in the city of Chicago ( N = 3,623 students ) . The adapted program achieved high participation levels ( 73 % ) overall , as well as in single parent families , non-English homes , and low-income students , among other at risk groups . Lower levels of factors associated with the onset of alcohol use ( i.e. , normative expectations and outcome expectations ) were achieved in the intervention group compared to the control group . However , no differences were observed for several other protective factors or alcohol use . Editors ' Strategic Implication s : The experimental design , large sample , and specific adaptation of the program for an ethnically diverse urban population of children and their families provide a model for culturally appropriate prevention efforts . Further , the attitudinal results ( and dose-response findings ) of the Slick Tracy alcohol prevention program are promising A r and omized trial tested the efficacy of three curriculum versions teaching drug resistance strategies , one modeled on Mexican American culture ; another modeled on European American and African American culture ; and a multicultural version . Self-report data at baseline and 14 months post-intervention were obtained from 3 , 402 Mexican heritage students in 35 Arizona middle schools , including 11 control sites . Tests for intervention effects used simultaneous regression models , multiple imputation of missing data , and adjustments for r and om effects . Compared with controls , students in the Latino version reported less overall substance use and marijuana use , stronger intentions to refuse substances , greater confidence they could do so , and lower estimates of substance-using peers . Students in the multicultural version reported less alcohol , marijuana , and overall substance use . Although program effects were confined to the Latino and multicultural versions , tests of their relative efficacy compared with the non-Latino version found no significant differences . Implication s for evidence -based practice and prevention program design s are discussed , including the role of school social workers in culturally grounded prevention OBJECTIVES : Criminally involved adolescents engage in high levels of alcohol-related risky sex . A theory-based sexual and alcohol risk-reduction intervention was design ed , implemented , and evaluated in juvenile detention facilities . Participants and Methods . In a r and omized , controlled trial , 484 detained adolescents received 1 of 3 group-based interventions : combined sexual and alcohol risk reduction ( group psychosocial intervention [ GPI ] + group motivational enhancement therapy [ GMET ] ) ; sexual risk reduction only ( GPI ) ; or HIV/sexually transmitted disease prevention information only ( group information-only intervention [ GINFO ] ) . Follow-up data were obtained 3 , 6 , 9 , and 12 months after the intervention . Behavioral outcomes were condom-use behavior , frequency of intercourse while drinking , and alcohol-related problems . RESULTS : Condom-use behavior measured as frequency of condom use during sex ( ranging from never to always ) decreased over time , although the GPI and GPI + GMET interventions mitigated this tendency at the 3- , 6- , and 9-month follow-up assessment s. Although both active interventions were significantly more successful than the GINFO condition and the pattern of effects favored the GPI + GMET , there were no statistically significant differences between the GPI and GPI + GMET interventions . CONCLUSIONS : Findings support the feasibility of integrating alcohol-specific sexual risk content into a theory-based sexual risk-reduction intervention and provide additional evidence that theory-based interventions are effective at reducing risky sex in this population . There was limited evidence of intervention effects on alcohol-use outcomes . Future research should focus on strengthening the GPI + GMET to most effectively target risky sexual behavior among at-risk adolescents The authors examined the effectiveness of a school-based prevention program on reducing binge drinking in a sample of minority , inner-city , middle-school students . Rates of binge drinking were compared among youth who received the program beginning in the 7th grade ( n = 1,713 ) and a control group ( n = 1,328 ) that did not . The prevention program had protective effects in terms of binge drinking at the 1-year ( 8th grade ) and 2-year ( 9th grade ) follow-up assessment s. The proportion of binge drinkers was over 50 % lower in the intervention group relative to the control group at the follow-up assessment s. There were also several significant program effects on proximal drinking variables , including drinking knowledge , pro-drinking attitudes , and peer drinking norms . These findings indicate that a school-based drug abuse prevention approach previously found to be effective among White youth significantly reduced binge drinking among urban minority youth A r and omized prevention trial contrasted families who took part in the Strong African American Families Program ( SAAF ) , a preventive intervention for rural African American mothers and their 11-year-olds , with control families . SAAF is based on a context ual model positing that regulated , communicative parenting causes changes in factors protecting youths from early alcohol use and sexual activity . Parenting variables included involvement-vigilance , racial socialization , communication about sex , and clear expectations for alcohol use . Youth protective factors included negative attitudes about early alcohol use and sexual activity , negative images of drinking youths , resistance efficacy , a goal -directed future orientation , and acceptance of parental influence . Intervention-induced changes in parenting mediated the effect of intervention group influences on changes in protective factors over a 7-month period The effectiveness of a 20 session cognitive-behavioral approach to substance abuse prevention was tested on seventh grade students ( n = 1,311 ) from 10 suburban New York junior high schools . The prevention strategy attempted to reduce intrapersonal pressure to smoke , drink excessively , or use marijuana by fostering the development of general life skills as well as teaching students tactics for resisting direct interpersonal pressure to use these substances . Additionally , this study was design ed to compare the relative effectiveness of this type of prevention program when implemented by either older peer leaders or regular classroom teachers . Results indicated that the prevention program had a significant impact on cigarette smoking , excessive drinking , and marijuana use when implemented by peer leaders . Furthermore , significant changes were also evident with respect to selected cognitive , attitudinal , and personality predisposing variables in a direction consistent with non-substance use . These results provide further support for the efficacy of a broad-spectrum smoking prevention strategy and tentative support for its applicability to the prevention of other forms of substance abuse The Strong African American Families Program , a universal preventive intervention to deter alcohol use among rural African American adolescents , was evaluated in a cluster-r and omized prevention trial . This 7-week family skills training program is based on a context ual model in which intervention effects on youth protective factors lead to changes in alcohol use . African American 11-year-olds and their primary caregivers from 9 rural communities ( N = 332 families ) were r and omly selected for study participation . Communities were r and omized to prevention and control conditions . Intent-to-treat analyses indicated that fewer prevention than control adolescents initiated alcohol use ; those who did evinced slower increases in use over time . Intervention-induced changes in youth protective factors mediated the effect of group assignment on long-term changes in use Substance use outcomes were examined for 351 youth participating in a r and omized controlled trial design ed to assess the efficacy of a school-based multimodal universal preventive intervention , Linking the Interests of Families and Teachers ( LIFT ) . Frequency of any use of tobacco , alcohol , and other drugs was assessed via self-report from grade s 5 through 12 . Latent variable growth models specified average level , linear growth and accelerated growth . The LIFT intervention had a significant effect on reducing the rate of growth in use of tobacco and illicit drugs , particularly for girls , and had an overall impact on average levels of use of tobacco , alcohol , and illicit drugs . Average tobacco use reductions were mediated by increases in family problem solving . The intervention had significant indirect effects on growth in substance use through intervention effects on reduced playground aggression and increased family problem solving . The intervention was also associated with roughly a 10 % reduced risk in initiating tobacco and alcohol use . Implication s for future studies of multimodal preventive interventions are discussed This study was design ed to test the efficacy of Parents Who Care © ( PWC ) , a seven-session universal prevention program which includes parenting , youth , and family components design ed to prevent substance use and other problem behaviors . Using an intent-to-treat experimental design , this study tests the program efficacy across race within a balanced sample of European American ( EA ) and African American ( AA ) youth and their parents ( n = 331 nAA = 163 ; nEA = 168 ) . Families were recruited , r and omly assigned to three conditions ( group-administered [ PA ] , self-administered with telephone support [ SA ] , and no-treatment control ) and the intervention was administered when the adolescents were in the eighth grade . Analyses on key teen outcomes of the Parent ’s Who Care program at 24-month follow-up are reported here and include perceptions of drug use harm ; favorable attitudes about drug use ; delinquent and violent behavior ; and initiation into cigarette , alcohol , other drug use , or sexual activity . Repeated measures mixed model regressions found no effect of the intervention on rate of change in attitudes about drug use or frequency of delinquent or violent behavior . Regression analyses with multiple imputations for missing data detected group differences in means at 24-month follow-up . Both program formats reduced favorable attitudes toward drug use among youth ( SA d = 0.39 , PA d = 0.22 ) ; and AA youth in the self-administered intervention reported significantly less violent behavior than their control counterparts ( d = 0.45 ) . No effects were found for drug use harm or delinquency . Finally , logistic regression predicting a combined outcome measure of initiation of alcohol , tobacco , drug use , and /or sexual activity found AA youth in both the group- and self-administered intervention conditions significantly less likely to initiate substance use and /or sexual activity than those in the control condition . Odds ratios indicated the chances of initiating sex or substance use were reduced by almost 70 % ( OR = 0.31 ) for AA teens in the SA condition compared to controls , and 75 % ( OR = 0.25 ) for the AA teens in the PA compared to controls This paper describes the third and final evaluation of drug education conducted by the Napa Project . In the present course students were taught decision-making skills , personal goal setting , a motivational model , peer and media influences on behavior , assertiveness training , and information on the consequences of , and alternatives to , alcohol , cigarette , and marijuana use . The evaluation employed an experimental design in which seventh grade classes in two schools were matched and then r and omly assigned to experimental and control conditions . Pre- , post- , and follow-up tests covered drug knowledge ; drug attitudes ; perceived benefits and costs of substance use ; perceived peer attitudes toward , and use of , substances ; and intentions to use , current use and lifetime use of various substances . The posttest and follow-up data were analyzed using hierarchical analyses of covariance controlling for corresponding pretest scores . The course was found to have had no significant effect on girls and only a few effects at follow-up for boys In this article , the authors examine whether delayed substance initiation during adolescence , achieved through universal family-focused interventions conducted in middle school , can reduce problematic substance use during young adulthood . Sixth- grade students enrolled in 33 rural midwestern schools and their families were r and omly assigned to 3 experimental conditions . Self-report question naires provided data at 7 time points for the Iowa Strengthening Families Program ( ISFP ) , Preparing for the Drug Free Years ( PDFY ) , and control groups through young adulthood . Five young adult substance frequency measures ( drunkenness , alcohol-related problems , cigarettes , illicit drugs , and polysubstance use ) were modeled as distal outcomes affected by the average level and rate of increase in substance initiation across the adolescent years in latent growth curve analyses . Results show that the models fit the data and that they were robust across outcomes and interventions , with more robust effects found for ISFP . The addition of direct intervention effects on young adult outcomes was not supported , suggesting long-term effects were primarily indirect . Relative reduction rates were calculated to quantify intervention-control differences on the estimated proportion of young adults indicating problematic substance use ; they ranged from 19 % to 31 % for ISFP and from 9 % to 16 % for PDFY This study examined the long-term substance use outcomes of 2 brief interventions design ed for general population families of young adolescents . Thirty-three public schools were r and omly assigned to 3 conditions : the 5-session Preparing for the Drug Free Years Program , the 7-session Iowa Strengthening Families Program , and a minimal contact control condition . The pretest involved 667 6th grade rs and their families . Assessment s included multiple measures of initiation and current use of alcohol , tobacco , and marijuana . Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade . Significant intervention-control differences in initiation and current use were found for both interventions . It is concluded that brief family skills-training interventions design ed for general population s have the potential to reduce adolescent substance use and thus have important public health implication An alternatives-oriented , school-based drug abuse prevention program , Positive Alternatives for Youth ( PAY ) , was evaluated over a 2-year period . Using a r and om-assignment , pretest-posttest control group design , 135 PAY students and 106 control group students were assessed on several attitudinal and behavioral measures of drug use . During the first year significant differences were detected between PAY and control students . Fewer differences were found in the second year , although a special analysis showed evidence of impact on PAY students rated as more involved in program activities . Reasons for specific results are discussed and implication s are drawn for the alternatives approach and the field of drug abuse prevention Two drug abuse prevention curricula were tested to determine their efficacy in preventing the onset of tobacco , alcohol , and marijuana use among adolescents . The first program focused on prevention through social pressure resistance training . The second featured affective education approaches to prevention . Curricula were tested on seventh grade students . Subjects were pretested just prior to the program and were post-tested at 12 and 24 months . Post-test analyses indicated that the social program delivered to seventh grade subjects was effective in delaying the onset of tobacco , alcohol , and marijuana use . No preventive effect of the affective education program was observed . By the final post-test , classrooms that had received the affective program had significantly more drug use than controls Objective : In the current study , the authors assessed whether a new online alcohol-misuse prevention course ( College Alc ) is more effective at reducing alcohol use and related consequences among drinkers and nondrinkers . Participants : The authors compared incoming college freshmen who reported any past 30-day alcohol use before the beginning of the semester with those who did not . Method Summary : The authors r and omly assigned students who completed a precollege baseline survey to either complete a 3-hour noncredit version of College Alc or serve as members of a control group . The authors conducted a follow-up survey 3 months later . Results : Findings indicated that among freshmen who were regular drinkers before college , College Alc appeared to reduce the frequency of heavy drinking , drunkenness , and negative alcohol-related consequences . Among freshmen who did not report any past-30-day alcohol use before college , College Alc did not appear to have any beneficial effects . Conclusions : Results suggest that College Alc may be an effective program for students with a history of alcohol use This study tests for the efficacy of a school-based drug prevention curriculum ( Think Smart ) that was design ed to reduce use of Harmful Legal Products ( HLPs , such as inhalants and over-the-counter drugs ) , alcohol , tobacco , and other drugs among fifth- and sixth- grade students in frontier Alaska . The curriculum consisted of 12 core sessions and 3 booster sessions administered 2 to 3 months later , and was an adaptation of the Schinke life skills training curriculum for Native Americans . Fourteen communities , which represented a mixture of Caucasian and Alaska Native population s in various regions of the state , were r and omly assigned to intervention or control conditions . Single items measuring 30-day substance use and multi-item scales measuring the mediators under study were taken from prior studies . Scales for the mediators demonstrated satisfactory construct validity and internal reliability . A pre-intervention survey was administered in classrooms in each school in the fall semester of the fifth and sixth grade s prior to implementing the Think Smart curriculum , and again in the spring semester immediately following the booster session . A follow-up survey was administered 6 months later in the fall semester of the sixth and seventh grade s. A multi-level analysis found that the Think Smart curriculum produced a decrease ( medium size effect ) in the proportion of students who used HLPs over a 30-day period at the 6 month follow-up assessment . There were no effects on other drug use . Further , the direct effect of HLPs use was not mediated by the measured risk and protective factors that have been promoted in the prevention field . Alternative explanations and implication s of these results are discussed Violence is an important public health problem among adolescents in the United States . Substance use and violence tend to co-occur among adolescents and appear to have similar etiologies . The present study examined the extent to which a comprehensive prevention approach targeting an array of individual-level risk and protective factors and previously found effective in preventing tobacco , alcohol , and illicit drug use is capable of decreasing violence and delinquency . Schools ( N=41 ) were r and omly assigned to intervention and control conditions . Participants in the 20 intervention schools received the Life Skills Training prevention program including material focusing on violence and the media , anger management , and conflict resolution skills . Survey data were collected from 4,858 sixth grade students prior to the intervention and three months later after the intervention . Findings showed significant reductions in violence and delinquency for intervention participants relative to controls . Stronger prevention effects were found for students who received at least half of the preventive intervention . These effects include less verbal and physical aggression , fighting , and delinquency . The results of this study indicate that a school-based prevention approach previously found to prevent tobacco , alcohol , and illicit drug use can also prevent violence and delinquency OBJECTIVES Although several studies have reported short-term gains for drug-use prevention programs targeted at young adolescents , few have assessed the long-term effects of such programs . Such information is essential for judging how long prevention benefits last . This paper reports results over a 6-year period for a multisite r and omized trial that achieved reductions in drug use during the junior high school years . METHODS The 11-lesson curriculum , which was tested in 30 schools in eight highly diverse West Coast communities , focused on helping 7th and 8th grade students develop the motivation and skills to resist drugs . Schools were r and omly assigned to treatment and control conditions . About 4000 students were assessed in grade 7 and six times thereafter through grade 12 . Program effects were adjusted for pretest covariates and school effects . RESULTS Once the lessons stopped , the program 's effects on drug use stopped . Effects on cognitive risk factors persisted for a longer time ( many through grade 10 ) , but were not sufficient to produce corresponding reductions in use . CONCLUSIONS It is unlikely that early prevention gains can be maintained without additional prevention efforts during high school . Future research is needed to develop and test such efforts OBJECTIVE To reduce tobacco use among adolescents . METHODS Thirty schools in New Delhi , India , were r and omly assigned to 3 conditions : school-based and family-based intervention , school-based intervention only , or control group . Students were in the seventh grade at pretest ( N = 4,776 ) . The smoking intervention included posters , booklets , classroom activities , debates , and a signature campaign . The family intervention involved home activities . The survey measured tobacco knowledge , attitudes , offers , use , and intentions . RESULTS Intervention students were significantly less likely than controls to have been offered , received , experimented with , or have intentions to use tobacco . CONCLUSION The project had a significant impact on tobacco use The purpose of the study was to evaluate the impact of the Going Places Program and mediation of treatment effects . Seven middle schools were r and omized to intervention or comparison conditions and students ( n = 1,320 ) in two successive cohorts provided five waves of data from sixth through eighth grade . The Going Places Program included classroom curriculum , parent education , and school environment components . Latent growth curve analyses demonstrated significant treatment group effects on outcome expectancies , friends who smoke , and smoking . Friends who smoke mediated the program effect on adolescents ’ smoking progression . The protective effect of the Going Places Program on smoking progression was due in part to the prevention of increases in friends who smoke BACKGROUND Two strategies for preventing the onset of alcohol abuse , and marijuana and cigarette use were tested in junior high schools in Los Angeles and Orange Counties , California . The first strategy taught skills to refuse substance use offers . The second strategy corrected erroneous normative perceptions about prevalence and acceptability of use among peers and established conservative groups norms regarding use . METHODS Four experimental conditions were created by r and omly assigning schools to receive ( a ) neither of the experimental curricula ( placebo comparison ) , ( b ) resistance skill training alone , ( c ) normative education alone , or ( d ) both resistance skill training and normative education . Students were pretested prior to the program and post-tested 1 year following delivery of the program . RESULTS There were main effects of normative education for summary measures of alcohol ( P = 0.0011 ) , marijuana ( P = 0.0096 ) , and cigarette smoking ( P = 0.0311 ) . All individual dichotomous measures of alcohol , marijuana , and tobacco use indicated significant reductions in onset attributable to normative education . There were no significant main effects of resistance skill training . CONCLUSION These results suggest that establishing conservative norms is an effective strategy for preventing substance use The distal impact of a school based universal preventive intervention targeting disruptive behavior problems on tobacco and alcohol use from age 10 to 13 years was explored . Second grade classrooms ( children aged 7 years ) were r and omly assigned to the intervention or a control condition . Tobacco and alcohol use from age 10 to 13 years was available for 477 children ( 72 % of original sample ) . The impact of intervention on the initial level and growth in probability of substance use was explored . Results showed that intervention children had lower probabilities of tobacco use over the ages 10 - 13 years . This effect remains significant when controlling for ( male ) sex , pre-intervention levels of conduct problems , exposure to prenatal smoking or current parental smoking . For alcohol use , no effect of intervention during childhood was found . However , intervention children reported having a lower probability in alcohol use with age among those children reporting having used in the last week . The results underscore the importance of the early prevention of disruptive behavior problems substance use initiation . Implication s for prevention and research are discussed OBJECTIVE Early age of drinking onset has been associated with a greater likelihood among adults of experiencing alcohol dependence , frequent heavy drinking even among nondependent drinkers , and an increased risk of motor vehicle crashes , unintentional injuries , and physical fights after drinking . This study explores whether first getting drunk at a younger age is associated with a greater likelihood of college students reporting that they had unplanned or unprotected sexual intercourse because of their drinking . METHODOLOGY In 1999 11 739 full-time 4-year college students from 128 r and omly selected US colleges and universities completed a self-administered survey that asked them about their drinking practice s and whether their drinking had caused them , since the beginning of the school year , to : 1 ) engage in unplanned sexual intercourse or 2 ) not use protection when having sex . RESULTS Among college students who drink , those first drunk before age 13 compared with those never drank until age 19 or older had a 2.0 times greater odds of having unplanned sex and a 2.2 times greater odds of having unprotected sex reportedly because of drinking , even after controlling for age , race/ethnicity , marital status , parental drinking history , age of first smoking , and marijuana use . After further controlling for history of alcohol dependence and frequency of heavy drinking those first drunk before age 13 had a 1.5 times greater odds of unplanned sex and a 1.7 times greater odds of unprotected sex reportedly because of drinking . CONCLUSIONS Clinical , educational , legal , and community interventions to delay age of first getting drunk need to be coupled with efforts to prevent unplanned and unprotected sexual intercourse among US college students The B.R.A.D. Birthday Card initiative was started on the campus of Michigan State University ( MSU ) in April 1999 . MSU administrators send the safe-drinking 21st birthday card ( B.R.A.D. ) and laminated wallet card to students shortly before their 21st birthday . Objective : To evaluate the effectiveness of the 21st birthday card , MSU and B.R.A.D. , Inc , applied for and were awarded a 2-year US Department of Education grant in 2001 . Participants : The authors surveyed 1,731 students within 2 weeks of their 21st birthday . Methods : Of all students turning 21 years old during the study , the authors r and omly selected students for each group . A control group received no card . All others received the st and ard B.R.A.D. card or a gender-tailored message card . Results : Key findings include : 74 % of students saved part of the card , 65 % shared the card with family or friends , 22 % reported thinking about the card during their celebration , 12 % reported drinking less because of the card , 15 % reported learning something new about alcohol poisoning , and 98 % believed that MSU and B.R.A.D. should continue sending cards to students . Conclusions : Receiving , reading , and recalling the content of the B.R.A.D. card appears to reduce the total number of drinks a celebrant consumes This study evaluates the Especially for Daughters intervention , which aims to provide urban Black and Latino parents with information and skills to support their daughters in delaying sexual initiation and alcohol use . In a r and omized field trial , 268 families with sixth- grade rs were recruited from New York City public schools and assigned either to the intervention , a set of audio CDs mailed home ; an attention-controlled condition ( print material s ) ; or controls . Girls completed classroom baseline and three follow-up surveys , and telephone surveys were conducted with parents . At follow-up , girls in the intervention reported fewer sexual risks ( adjusted odds ratio [ AOR ] = 0.39 , confidence interval [ CI ] = 0.17 - 0.88 ) and less drinking ( AOR = 0.38 , CI = 0.15 - 0.97 , p < .05 ) . Their parents reported greater self-efficacy to address alcohol and sex and more communication on these topics . This gender-specific parent education program was for communities with high rates of HIV , where early sexual onset is common and often fueled by alcohol An elementary school social skills/peer pressure resistance curriculum for the prevention of alcohol misuse was developed , implemented , and evaluated . Schools were r and omly assigned to curriculum and control groups , with half of each group pretested prior to intervention and all students posttested two months , 14 months , and 26 months following intervention . Students in grade five at the beginning of the study were r and omly assigned to treatment , treatment plus booster , and control conditions . Students in grade six were r and omly assigned to treatment and control conditions . Three way repeated measures analyses of covariance ( treatment condition by type of prior drinking experience by occasion ) were conducted for each grade level on indices of " frequency/quantity of alcohol use " and " total alcohol misuse . " Results indicated the intervention was effective in reducing the rate of increase of alcohol use and misuse among grade six students who entered the study with prior unsupervised as well as supervised alcohol use . After corrections for intraclass correlations on the dependent variables , the significant finding regarding the alcohol misuse variable was maintained The current study examined the impact of a brief motivational interviewing ( MI ) intervention ( Project CHAT ) on alcohol consumption and drug use for high-risk teens in a primary care clinic that provides health care for underserved population s. Youth ( N=42 , 48 % male ) were screened , and those eligible completed a baseline survey . Baseline survey completers were r and omly assigned to usual care or to an MI intervention and completed a 3-month follow-up survey . The sample ( age 12 to 18 years ) was 85.7 % Hispanic or Latino , 9.5 % African American , and 4.8 % White . At the 3-month follow-up , Project CHAT teens reported less marijuana use , lower perceived prevalence of marijuana use , fewer friends who used marijuana , and lower intentions to use marijuana in the next 6 months , as compared to teens assigned to usual care . Providing this type of brief intervention is a viable approach to working with high-risk teens to decrease substance use Thirty-four schools ( n=7426 consented sixth grade rs , 71 % of the eligible population ) were r and omized to conditions to test the hypothesis that Skills for Adolescence ( SFA ) , a widely used comprehensive life skills training curriculum with a dedicated drug education unit , is more effective than st and ard care in deterring and delaying substance use through middle school . Two-year posttest ( 1-year post-intervention ) data were collected from 5691 eighth grade rs ( 77 % of those who completed the sixth- grade survey and 87 % of those who completed the seventh- grade survey ) . Lifetime and recent ( last 30 days ) use of five substances or combinations of substances was compared using mixed-model regression to control for school clustering . There were two significant treatment main effects at the end of the eighth grade : lifetime ( P=.05 ) and recent ( P<.03 ) marijuana use were lower in SFA than control schools with pretest usage and salient demographic and psychosocial variables controlled . There was also one significant Treatment x Pretest Usage interaction around binge drinking . Baseline binge drinkers in SFA schools were less likely to report recent binge drinking than students in control schools ( P<.01 ) ; there were no treatment differences among baseline nonbinge drinkers . Analyses of potential mediators of SFA treatment effects on eighth- grade binge drinking and marijuana use suggested that SFA increased self-efficacy around drug refusal skills , but did not affect behavioral intentions , perceptions of harm , or perceived peer norms . These 2-year ( 1-year post-intervention ) outcomes offer some additional support for SFA effectiveness and the general thrust of school-based , life skills-based prevention programs . The promising sixth- through eighth- grade findings for SFA , a commercially available program , provide a further step in bridging a major gap in the " research to practice " literature : theory-based interventions that have documented behavioral effects have not enjoyed large-scale implementation , while intuition-based programs that have no documented effects still enjoy wide exposure Sensation seeking , anxiety sensitivity , and hopelessness are personality risk factors for alcohol use disorders , each associated with specific risky drinking motives in adolescents . We developed a set of interventions and manuals that were design ed to intervene at the level of personality risk and associated maladaptive coping strategies , including alcohol misuse . Manuals contained psychoeducational information on the target personality risk factor and how it is associated with maladaptive coping , as well as exercises targeting maladaptive cognitions and behaviors specific to each personality type . We tested the efficacy of these novel interventions on reducing drinking behavior by r and omly assigning 297 Canadian high school students ( 56 % girls , mean age 16 , mean grade 11 ) to personality-targeted interventions ( group format ; 2 sessions ) or to a no-treatment control group . Intent-to-treat analyses indicated beneficial effects of the intervention and Intervention × Personality interactions on drinking rates , drinking quantity , binge drinking , and problem drinking symptoms at 4-month follow-up This study tested a computerized gender-specific , parent-involvement intervention program grounded in family interaction theory and aim ed at preventing substance use among adolescent girls . Following program delivery and 1 year later , girls r and omly assigned to the intervention arm improved more than girls in a control arm on variables associated with reduced risks for substance use , including communication with their mothers , knowledge of family rules about substance use , awareness of parental monitoring of their discretionary time , non-acceptance of peer substance use , problem-solving skills , and ability to refuse peer pressure to use substances . Relative to control-arm girls , those in the intervention arm also reported less 30-day use of alcohol and marijuana and lower intentions to smoke , drink , and take illicit drugs in the future . Girls ' mothers in the intervention arm reported greater improvements after the program and relative to control-arm mothers in their communication with their daughters , establishment of family rules about substance use , and monitoring of their daughters ' discretionary time . Study findings lend support to the potential of gender-specific , parent-involvement , and computerized approaches to preventing substance use among adolescent girls Two versions of a school-based alcohol prevention programme for 7th grade students were evaluated against a non-treated comparison condition . Both programme versions were based on a social-cognitive theory approach to alcohol prevention , and differed in the level of role-specifications for participating teachers and peer leaders . Twelve schools with 955 students in Bergen , Norway , participated in the study . Four schools were r and omly assigned to each of the three conditions , and the programme was implemented during 10 class periods over 2 months in Spring , 1992 . Pre- and post-test surveys were conducted , assessing alcohol use , as well as cognitive variables related to alcohol use in a specific context ( intentions , attitudes , norms and self-efficacy expectations ) . Results showed that the highly role-specified ( HRS ) version had a higher degree of student involvement than the less role-specified ( LRS ) version , indicating that the HRS programme was more successful in engaging students in alcohol prevention activities . A significant difference in programme effectiveness was found , as measured by an overall programme effect across all dependent variables . This effect was explained by significantly more positive outcomes in the HRS version compared to both the LRS and the non-treated conditions , while the LRS version did not differ significantly from the non-treated condition OBJECTIVES This study explored whether college students who were first intoxicated by alcohol at ages younger than 19 are more likely to become alcohol dependent and frequent heavy drinkers , drive after drinking , ride with intoxicated drivers and be injured after drinking . It also investigated whether these results occur because these students believe they can drink more and still drive legally and safely . METHOD In 1999 , 14,138 of 23,751 full-time 4-year students from a r and om sample of 119 college and universities nationwide completed self-administered question naires ( response rate : 60 % ) . This analysis focused on 12,550 who were aged 19 or older . Respondents were asked the age at which they first got drunk , as well as questions about recent alcohol-related behaviors and consequences . RESULTS Compared with respondents first drunk at age 19 or older , those first drunk prior to age 19 were significantly more likely to be alcohol dependent and frequent heavy drinkers , to report driving after any drinking , driving after five or more drinks , riding with a driver who was high or drunk and , after drinking , sustaining injuries that required medical attention . Respondents first intoxicated at younger ages believed they could consume more drinks and still drive safely and legally ; this contributed to their greater likelihood of driving after drinking and riding with high or drunk drivers . CONCLUSIONS Educational , clinical , environmental and legal interventions are needed to delay age of first intoxication and to correct misperceptions among adolescents first drunk at an early age about how much they can drink and still drive safely and legally AIMS To evaluate the effectiveness of two preventive interventions to reduce heavy drinking in first- and second-year high school students . DESIGN AND SETTING Cluster r and omized controlled trial using four conditions for comparing two active interventions with a control group from 152 classes of 19 high schools in the Netherl and s. PARTICIPANTS A total of 3490 first-year high school students ( mean 12.68 years , SD=0.51 ) and their parents . Intervention conditions ( i ) Parent intervention ( modelled on the Swedish Örebro Prevention Program ) aim ed at encouraging parental rule- setting concerning their children 's alcohol consumption ; ( ii ) student intervention consisting of four digital lessons based on the principles of the theory of planned behaviour and social cognitive theory ; ( iii ) interventions 1 and 2 combined ; and ( iv ) the regular curriculum as control condition . Main outcome measures Incidence of ( heavy ) weekly alcohol use and frequency of monthly drinking at 10 and 22 months after baseline measurement . FINDINGS A total of 2937 students were eligible for analyses in this study . At first follow-up , only the combined student-parent intervention showed substantial and statistically significant effects on heavy weekly drinking , weekly drinking and frequency of drinking . At second follow-up these results were replicated , except for the effects of the combined intervention on heavy weekly drinking . These findings were consistent across intention-to-treat and completers-only analyses . CONCLUSIONS Results suggest that adolescents as well as their parents should be targeted in order to delay the onset of drinking , preferably prior to onset of weekly drinking AIMS This study examines the efficacy of the Focus on Families project ( currently called Families Facing the Future ) , a preventive intervention to reduce substance use disorders among children in families with a parent in methadone treatment . DESIGN One hundred and thirty families were assigned r and omly to a methadone clinic treatment-as-usual control condition or treatment-as-usual plus the Focus on Families intervention between 1991 and 1993 . Setting Participants were recruited from two methadone clinics in the Pacific Northwest . PARTICIPANTS This study examines the development of substance use disorders among the 177 children ( 56.84 % male ) involved in the program using data from a long-term follow-up in 2005 , when these participants ranged in age from 15 to 29 years . INTERVENTION The intervention was delivered through group parent-training workshops at the methadone clinics and through individualized home-based services . The intervention taught parenting skills and skills for avoiding relapse to drug abuse . MEASUREMENTS At long-term follow-up , substance use disorders were measured by the Composite International Diagnostic Interview ( CIDI ) . Survival analyses were used to assess intervention versus control differences in the hazard of developing substance use disorders . FINDINGS Overall , intervention and control participants did not differ significantly in risk of developing substance use disorders . However , there was evidence of a significant difference in intervention effect by gender . There was a significant reduction in the risk of developing a substance use disorder for intervention group males compared to control group males ( hazard ratio = 0.53 , P = 0.03 ) , while intervention versus control differences among females were non-significant and favored the control condition . CONCLUSIONS Results from this study suggest that helping parents in recovery focus on both reducing their drug use and improving their parenting skills may have long-term effects on reducing substance use disorders among their male children . However , the overall long-term benefits of this program are not supported by the results for female children OBJECTIVES To implement and to assess the efficacy of a school-based , sport team-centered program to prevent young female high school athletes ' disordered eating and body-shaping drug use . DESIGN AND SETTING Prospect i ve controlled trial in 18 high schools , with balanced r and om assignment by school to the intervention and usual-care control conditions . PARTICIPANTS We enrolled 928 students from 40 participating sport teams . Mean age was 15.4 years , 92.2 % were white , and follow-up retention was 72 % . INTERVENTION The ATHENA ( Athletes Targeting Healthy Exercise and Nutrition Alternative ) curriculum 's 8 weekly 45-minute sessions were incorporated into a team 's usual practice activities . Content was gender-specific , peer-led , and explicitly scripted . Topics included healthy sport nutrition , effective exercise training , drug use and other unhealthy behaviors ' effects on sport performance , media images of females , and depression prevention . MAIN OUTCOME MEASURES We assessed participants by confidential question naire prior to and following their sport season . We determined program effects using an analysis of covariance-based approach within the Generalized Estimating Equation framework . RESULTS Experimental athletes reported significantly less ongoing and new use of diet pills and less new use of athletic-enhancing substances ( amphetamines , anabolic steroids , and sport supplements ) ( P<.05 for each ) . Other health-harming actions also were reduced ( less riding with an alcohol-consuming driver [ P = .05 ] , more seat belt use [ P<.05 ] , and less new sexual activity [ P<.05 ] ) . The ATHENA athletes had coincident positive changes in strength-training self-efficacy ( P<.005 ) and healthy eating behaviors ( P<.001 ) . Reductions occurred in intentions toward future use of diet pills ( P<.05 ) , vomiting to lose weight ( P<.05 ) , and use of tobacco ( P<.05 ) and muscle-building supplements ( P<.005 ) . The program 's curriculum components were altered appropriately ( controlling mood [ P<.005 ] , refusal skills [ P = .05 ] , belief in the media [ P<.005 ] , and perceptions of closest friends ' body-shaping drug use [ P<.001 ] ) . CONCLUSIONS Sport teams are effective natural vehicles for gender-specific , peer-led curricula to promote healthy lifestyles and to deter disordered eating , athletic-enhancing substance use , and other health-harming behaviors AIMS To establish the long-term efficacy of a universal internet-based alcohol and cannabis prevention programme in schools . METHODS A cluster-r and omized controlled trial was conducted to assess the effectiveness of the Climate Schools : Alcohol and Cannabis Course . The evidence -based course , aim ed at reducing alcohol and cannabis use , is facilitated by the internet and consists of 12 novel and curriculum consistent lessons delivered over 6 months . PARTICIPANTS A total of 764 year 8 students ( 13 years ) from 10 Australian secondary schools were allocated r and omly to the internet-based prevention programme ( n = 397 , five schools ) , or to their usual health classes ( n = 367 , five schools ) . MEASURES Participants were assessed at baseline , immediately post , and 6 and 12 months following completion of the intervention , on measures of alcohol and cannabis knowledge , attitudes , use and related harms . RESULTS This paper reports the final results of the intervention trial , 12 months following the completion of the Climate Schools : Alcohol and Cannabis Course . The effectiveness of the course 6 months following the intervention has been reported previously . At the 12-month follow-up , compared to the control group , students in the intervention group showed significant improvements in alcohol and cannabis knowledge , a reduction in average weekly alcohol consumption and a reduction in frequency of drinking to excess . No differences between groups were found on alcohol expectancies , cannabis attitudes or alcohol- and cannabis-related harms . The course was found to be acceptable by teachers and students as a means of delivering drug education in schools . CONCLUSIONS Internet-based prevention programs for school-age children can improve student 's knowledge about alcohol and cannabis , and may also reduce alcohol use twelve months after completion AIMS To examine the effects of a parent and student intervention offered separately and simultaneously ( PAS ) on onset of weekly drinking via its putative mediators . DESIGN A r and omized trial with four conditions ; ( 1 ) parent intervention , ( 2 ) student intervention , ( 3 ) combined parent-student intervention and ( 4 ) control group . SETTING High schools selected r and omly , located in different areas . PARTICIPANTS A total of 2937 early adolescents ( mean age = 12.6 , st and ard deviation = 0.49 ) and their parents . MEASUREMENTS Mediation effects were analysed using pretest data and two follow-up measurements ( 10 and 22 months after baseline ) . A path model was estimated ( Mplus ) to examine the effect of the interventions on adolescent-reported mediators ( self-control , perceived parental rules and attitudes about alcohol ) and parent-reported mediators ( parental rules and attitudes about alcohol ) . Outcome was onset of weekly drinking . FINDINGS The parent intervention modified rules and attitudes about alcohol as reported by parents . An indirect effect of the parent intervention via parental rules was found . The combined intervention affected both adolescent-reported and parent-reported rules and attitudes about alcohol and adolescents ' perceived self-control , yet only perceived rules and self-efficacy , as reported by adolescents , and parental attitudes mediated the association between the combined intervention and onset of weekly drinking . No significant effects were found of the separate student intervention on the mediating factors . CONCLUSIONS The PAS programme proved to be effective as predicted by the theoretical assumptions underlying the interventions . Interventions with parents and adolescents to prevent adolescent alcohol consumption may usefully target parental rules about alcohol and adolescents ' self-confidence BACKGROUND Personality factors are implicated in the vulnerability to adolescent alcohol misuse . This study examined whether providing personality-targeted interventions in early adolescence can delay drinking and binge drinking in high-risk youth . METHODS A r and omised control trial was carried out with 368 adolescents recruited from years 9 and 10 ( median age 14 ) with personality risk factors for substance misuse . Participants received either a personality-targeted intervention or no intervention . Outcome data were collected on alcohol use through self-reports at 6 and 12-month post intervention and analyses were conducted on the full intent to treat sample . RESULTS Multi-group analysis of a latent growth curve model showed a group difference in the growth of alcohol use between baseline and 6-months follow-up , with the control group showing a greater increase in drinking than the intervention group for this period . Interventions were particularly effective in preventing the growth of binge drinking in those students with a sensation seeking ( SS ) personality . SS drinkers in the intervention group were 45 % and 50 % less likely to binge drink at 6 ( OR = .45 ) and 12 months ( OR = .50 ) respectively , than SS drinkers in the control group , p = .001 , phi = .49 , Number Needed to Treat = 2.0 . CONCLUSIONS Considering the robust , inverse relationship between age of onset of alcohol use and later alcohol dependence , this intervention strategy may prove effective in preventing the onset of adult alcohol use disorders , by helping high-risk youth delay the growth of their drinking to a later developmental stage OBJECTIVE To establish the efficacy of an internet based prevention program to reduce alcohol and cannabis use in adolescents . METHOD A cluster r and omised controlled trial was conducted with 764 13-year olds from ten Australian secondary schools in 2007 - 2008 . Half the schools were r and omly allocated to the computerised prevention program ( n=397 ) , and half to their usual health classes ( n=367 ) . The Climate Schools : Alcohol and Cannabis prevention course is facilitated by the internet and consists of novel , evidence -based , curriculum consistent lessons aim ed at reducing alcohol and cannabis use . Participants were assessed at baseline , immediately post , and at six months following the intervention . RESULTS Compared to the control group , students in the intervention group showed significant improvements in alcohol and cannabis knowledge at the end of the course and the six month follow-up . In addition , the intervention group showed a reduction in average weekly alcohol consumption and frequency of cannabis use at the six month follow-up . No differences between groups were found on alcohol expectancies , cannabis attitudes , or alcohol and cannabis related harms . CONCLUSIONS The course is acceptable , scalable and fidelity is assured . It increased knowledge regarding alcohol and cannabis , and decreased use of these drugs OBJECTIVE To test a computer-delivered program for preventing substance use among adolescent girls . METHODS R and omly , 916 girls aged 12.76+/-1.0 years and their mothers were assigned to an intervention arm or to a test-only control arm . Intervention-arm dyads engaged in exercises to improve the mother-daughter relationship , build girls ' substance use prevention skills , and reduce associated risk factors . Study outcomes were girls ' and mothers ' substance use and mediator variables related to girls ' substance use risk and protective factors . The study was conducted between September 2006 and February 2009 with participants from greater New York City , including southern Connecticut and eastern New Jersey . RESULTS At 2-year follow-up and relative to control-arm girls , intervention-arm girls reported lower relevant risk factors and higher protective factors as well as less past 30-day use of alcohol ( p<0.006 ) , marijuana ( p<0.016 ) , illicit prescription drugs ( p<0.03 ) , and inhalants ( p<0.024 ) . Intervention-arm mothers showed more positive 2-year outcomes than control-arm mothers on variables linked with reduced risks of substance use among their daughters , and mothers reported lower rates of weekly alcohol consumption ( p<0.0001 ) . CONCLUSIONS A computer-delivered prevention program for adolescent girls and their mothers was effective in changing girls ' risk and protective factors and girls ' and mothers ' substance use behavior BACKGROUND The Good Behavior Game ( GBG ) is a classroom behavior management strategy focused on socializing children to the role of student and aim ed at reducing early aggressive , disruptive behavior , a confirmed antecedent to service use . The GBG was tested in a r and omized field trial in 19 elementary schools with two cohorts of children as they attended first and second grade s. This article reports on the impact of the GBG on service use through young adulthood . METHODS Three or four schools in each of five urban areas were matched and r and omly assigned to one of three conditions : ( 1 ) GBG , ( 2 ) an intervention aim ed at academic achievement , or ( 3 ) the st and ard program of the school system . Children were assigned to classrooms to ensure balance , and teachers and classrooms were r and omly assigned to intervention conditions . RESULTS This study provides evidence of a positive impact of a universal preventive intervention on later service use by males , although not by females , for problems with emotions , behavior , or drugs or alcohol . For both cohorts , males in GBG classrooms who had been rated as highly aggressive , disruptive by their teachers in the fall of first grade had a lower rate of school-based service use than their counterparts in control classrooms . REPLICATION : The design employed two cohorts of students . Although both first- and second- grade teachers received less training and support with the second cohorts of students than with the first cohort , the impact of GBG was similar across both cohorts This article reports adolescent substance use outcomes of universal family and school preventive interventions 5(1/2 ) years past baseline . Participants were 1677 7th grade students from schools ( N=36 ) r and omly assigned to the school-based Life Skills Training plus the Strengthening Families Program : For Parents and Youth 10 - 14 ( LST+SFP 10 - 14 ) , LST-alone , or a control condition . Self-reports were collected at baseline , 6 months later following the interventions , then yearly through the 12th grade . Measures included initiation-alcohol , cigarette , marijuana , and drunkenness , along with a Substance Initiation Index (SII)- and measures of more serious use-frequency of alcohol , cigarette , and marijuana use , drunkenness frequency , monthly poly-substance use , and advanced poly-substance use . Analyses ruled out differential attrition . For all substance initiation outcomes , one or both intervention groups showed significant , positive point-in-time differences at 12th grade and /or significant growth trajectory outcomes when compared with the control group . Although no main effects for the more serious substance use outcomes were observed , a higher-risk sub sample demonstrated significant , positive 12th grade point-in-time and /or growth trajectory outcomes for one or both intervention groups on all measures . The observed pattern of results likely reflects a combination of predispositions of the higher-risk sub sample , the timing of the interventions , and baseline differences between experimental conditions favoring the control group Purpose . This study examined whether brief intervention strategies founded on the Behavior-Image Model and addressing positive images of college and career success could be potentially efficacious in impacting multiple health habits of high-risk adolescents transitioning into adulthood . Design . Participants were stratified by grade level and drug use and individually r and omized to one of the three Plan for Success interventions , with baseline and 1 month postintervention data collection s. Setting . A large , relatively diverse suburban school in northeast Florida . Subjects . A total of 375 11th and 12th grade students participated during the spring semester 2006 . Intervention . Three interventions studied included : ( 1 ) Goal Survey , ( 2 ) Goal Survey plus Contract , or ( 3 ) Goal Survey plus Consult . Measures . Outcome measures included multiple health risk , health promotion , and personal development behaviors , as well as image and belief measures . Analysis . Repeated- measures MANOVAs and ANOVAs were used to examine intervention effects . Results . MANOVAs were significant for alcohol use , F(4,328 ) = 6.33 , p = .001 ; marijuana use , F(4,317 ) = 3.72 , p = .01 ; exercise , F(3,299 ) = 4.28 , p = .01 ; college preparation , F(2,327 ) = 6.26 , p = .001 ; and career preparation , F(2,329 ) = 6.17 , p = .001 , with most behaviors improving over time , whereas group-by-time interaction effects were found for nutrition habits , F(6,652 ) = 2.60 , p = .02 ; and career preparation , F(4,658 ) = 3.26 , p = .01 , favoring the consultation . Conclusion . Brief interventions founded on the Behavior-Image Model may have potential to improve selected health and personal development habits among older adolescents OBJECTIVE This report extends earlier accounts by addressing the effects of the Strong African American Families ( SAAF ) program across 65 months . Two hypotheses were tested : ( a ) Rural African American youths r and omly assigned to participate in SAAF would demonstrate lower rates of alcohol use than would control youths more than 5 years later , and ( b ) SAAF 's effects on deterring the onset of alcohol use in early adolescence would carry forward to mediate the program 's long-term effects . METHOD African American youths in rural Georgia ( mean age at pretest = 10.8 years ) were assigned r and omly to the SAAF group ( n = 369 ) or to a control group ( n = 298 ) . Past-month alcohol use was assessed at pretest and at 9 , 18 , 29 , 53 , and 65 months after pretest . RESULTS SAAF participants increased their alcohol use at a slower rate than did adolescents in the control condition across the follow-up assessment s. At the 65-month assessment , SAAF participants reported having drunk alcohol half as often as did youths in the control group . Consistent with the second hypothesis , SAAF 's effects on deterring initiation carried forward to account for its effects on alcohol use across time . CONCLUSIONS Training in protective parenting processes and self-regulatory skills during preadolescence may contribute to a self-sustaining trajectory of disinterest in and avoidance of alcohol use during adolescence when peers begin to model and sanction it |
12,415 | 29,106,307 | Evidence on menopause and asthma was conflicting , while studies on COPD were scarce .
The findings generally support an association between menopause and clinical ly significant reductions in lung function in a non-obstructive pattern .
However , the effects of menopause are clouded by aging , menopausal hormone therapy use , and increased risk of metabolic syndrome during this period . | BACKGROUND The menopausal transition may have significant consequences for respiratory health , risk of chronic respiratory disease and management strategies .
OBJECTIVE To systematic ally summarize the literature regarding the impact of menopause status on respiratory health outcomes . | Background Epidemiological studies have suggested that female hormones might play a role in asthma and that menopausal hormone therapy ( MHT or hormone replacement therapy ( HRT ) ) might increase the risk of asthma in postmenopausal women . The only prospect i ve study addressing this issue reports an increase in the risk of developing asthma which was similar for oestrogen alone and oestrogen/progestagen treatment . Methods The association between the use of different types of MHT and the risk of asthma onset in postmenopausal women was investigated prospect ively from 1990 to 2002 by biennial question naires as part of the French E3N cohort study . Asthma onset was considered to be the time of medical diagnosis of asthma cases occurring during the follow-up of women who were asthma free at baseline . Cox proportional hazards models were used , adjusting for potential confounding factors . Results Among 57 664 women free of asthma at menopause , 569 incident cases of asthma were identified during 495 448 years of follow-up . MHT was related to an increased risk of asthma onset ( HR=1.20 , 95 % CI 0.98 to 1.46 ) among recent users . The increase in risk of asthma onset was only significant among women reporting the use of oestrogen alone ( HR=1.54 , 95 % CI 1.13 to 2.09 ) particularly in never smokers ( HR=1.80 , 95 % CI 1.15 to 2.80 ) and women reporting allergic disease prior to asthma onset ( HR=1.86 , 95 % CI 1.18 to 2.93 ) . A small increase in the risk of asthma onset associated with the use of oestrogen/progestagen was also observed in these subgroups . Conclusion Postmenopausal use of oestrogen alone was associated with an increased rate of newly diagnosed asthma in menopausal women The protective effect of pregnancy on putative Th1-mediated autoimmune diseases , such as multiple sclerosis and rheumatoid arthritis , is associated with a Th1 to Th2 immune shift during pregnancy . The hormone estriol increases during pregnancy and has been shown to ameliorate experimental autoimmune encephalomyelitis and collagen-induced arthritis . In addition , estrogens induce cytokine changes consistent with a Th1 to Th2 shift when administered in vitro to human immune cells and in vivo to mice . In a pilot trial , oral estriol treatment of relapsing remitting multiple sclerosis patients caused significant decreases in enhancing lesions on brain magnetic resonance imaging . Here , the immunomodulatory effects of oral estriol therapy were assessed . P BMC s collected longitudinally during the trial were stimulated with mitogens , recall Ags , and glatiramer acetate . Cytokine profiles of stimulated P BMC s were determined by intracellular cytokine staining ( IL-5 , IL-10 , IL-12 p40 , TNF-α , and IFN-γ ) and cytometric bead array ( IL-2 , IL-4 , IL-5 , IL-10 , TNF-α , and IFN-γ ) . Significantly increased levels of IL-5 and IL-10 and decreased TNF-α were observed in stimulated P BMC isolated during estriol treatment . These changes in cytokines correlated with reductions of enhancing lesions on magnetic resonance imaging in relapsing remitting multiple sclerosis . The increase in IL-5 was primarily due to an increase in CD4 + and CD8 + T cells , the increase in IL-10 was primarily due to an increase in CD64 + monocytes/macrophages with some effect in T cells , while the decrease in TNF-α was primarily due to a decrease in CD8 + T cells . Further study of oral estriol therapy is warranted in Th1-mediated autoimmune diseases with known improvement during pregnancy OBJECTIVE To study whether hormone replacement therapy ( HRT ) or Tibolone has an effect on pulmonary function in postmenopausal women . METHODS Seventy-five postmenopausal women without any risk factor for pulmonary disease were included in this r and omized , prospect i ve study . Fifty women had undergone natural menopause and 25 had had a hysterectomy/ooforectomy . Twenty-five natural menopause women were r and omly allocated to two groups : 25 patients ( Group I ) were treated with Tibolone 2.5 mg/day , 25 patients ( group II ) with Estradiol Hemihidrate 2 mg+Norethindron Asetate 1 mg/day . Twenty-five induced menopause women were treated with 17 beta-estradiol 2 mg/day . Lung function tests including forced vital capacity ( FVC ) , forced expiratory volume ( FEV(1 ) ) , FEV(1)/FVC , forced expiratory flow rate over the 25 - 75 % of the forced vital capacity volume ( FEF(25 - 75 % ) ) , and peak expiratory flow rate ( PEF ) were evaluated at the beginning and 3 months after the treatment to assess the effects of HRT and Tibolone on respiratory function . RESULTS Regardless of HRT types a significant difference was observed in FVC and FEV(1 ) after 3 months of the therapy ( P=0.001 , 0.0001 , respectively ) . No significant difference was found between pre and post therapy values in the other parameters ( P>0.05 ) . CONCLUSIONS We determined a significant increase in FVC and FEV(1 ) parameters of pulmonary functions after 3 months of the therapy regardless of HRT types . Therefore , we think that HRT regimens have modifying effects on pulmonary function in postmenopausal women We prospect ively evaluated the association of hormone replacement therapy and asthma incidence in a cohort of pre- and postmenopausal women 34 to 68 yr of age . During 582 , 135 person-years of follow-up between 1980 and 1990 , 726 new cases of asthma were documented . Postmenopausal women who were never users of replacement hormones had a significantly lower age-adjusted risk of asthma than premenopausal women ( relative risk = 0.65 ; 95 % confidence interval [ CI ] = 0.46 to 0.92 ) . Among naturally menopausal women , the age-adjusted relative risk of asthma for ever use of postmenopausal hormones was 1.49 ( 95 % CI = 1.10 to 2.00 ) ; for current use of hormones ( conjugated estrogens with or without progesterone ) , 1.50 ( 95 % CI = 0.98 to 2.30 ) ; and for past use , 1.52 ( 95 % CI = 1.08 to 2.13 ) , compared with never use of hormones . Ever users of 10 or more years ' duration had twice the age-adjusted risk of asthma compared with women who never used postmenopausal hormones ( 95 % CI = 1.39 to 2.87 ) . Among current users of conjugated estrogens , there was a positive dose-response demonstrated between daily dose and asthma risk ( p for trend = 0.007 ) . While confirmatory studies are warranted , these data suggest that estrogen plays a role in the pathophysiology of asthma and that long-term use and /or high doses of postmenopausal hormone therapy increase subsequent risk of asthma Objective : To investigate the variability and determinants of menopause age in two European cohort studies , the European Respiratory Health Survey and the Swiss Air Pollution and Lung Disease in Adults Cohort . Methods : Age at menopause was estimated in 5,288 women , aged 30 to 60 years , r and omly selected in nine European countries between 1998 and 2002 . Determinants of natural and surgically induced menopause were investigated by Cox regression and heterogeneity by meta- analysis . Follicle-stimulating hormone and luteinizing hormone levels were assessed in a sub sample . Results : A quarter of the women were postmenopausal by age 50.8 years . Median age of natural menopause was 54 years . Hormone levels were within expected ranges for premenopausal and postmenopausal women . Surgically induced menopause was highly prevalent ( 22%-47 % ) , associated with earlier timing of menopause . Determinants of earlier menopause were current smoking ( hazard ratio [ HR ] , 1.59 ; 95 % CI , 1.27 - 1.98 ) , body mass index greater than 30 kg/m2 ( HR , 1.32 ; 95 % , CI , 1.02 - 1.70 ) , and low physical activity ( HR , 1.37 ; 95 % , CI , 1.12 - 1.67 ) . The determinant for later menopause was multiparity ( HR , 0.74 ; 95 % CI , 0.62 - 0.89 ) . Predictors were similar for naturally and surgically induced menopause . Oral contraceptive use yielded heterogeneous effects on timing of menopause . Later birth was associated with later menopause ( HR , 0.934 ; 95 % CI , 0.91 - 0.96 ) . This evidence of a secular trend is heterogeneous across countries . Conclusions : Age at menopause varies across Europe , shifting toward higher ages . This secular trend seems paradoxical because several adult determinants , that is , overweight , smoking , sedentarity , and nulliparity , associated with early menopause are on the rise in Europe . The heterogeneity of the secular trend suggests additional country-specific factors not included in the study , such as improved childhood nutrition and health , that have an influence on reproductive aging Abstract Objective : To assess the relation between forced expiratory volume in one second ( FEV1 ) and subsequent mortality . Design : Prospect i ve general population study . Setting : Renfrew and Paisley , Scotl and . Subjects : 7058 men and 8353 women aged 45 - 64 years at baseline screening in 1972 - 6 . Main outcome measure : Mortality from all causes , ischaemic heart disease , cancer , lung and other cancers , stroke , respiratory disease , and other causes of death after 15 years of follow up . Results : 2545 men and 1894 women died during the follow up period . Significant trends of increasing risk with diminishing FEV1 are apparent for both sexes for all the causes of death examined after adjustment for age , cigarette smoking , diastolic blood pressure , cholesterol concentration , body mass index , and social class . The relative hazard ratios for all cause mortality for subjects in the lowest fifth of the FEV1 distribution were 1.92 ( 95 % confidence interval 1.68 to 2.20 ) for men and 1.89 ( 1.63 to 2.20 ) for women . Corresponding relative hazard ratios were 1.56 ( 1.26 to 1.92 ) and 1.88 ( 1.44 to 2.47 ) for ischaemic heart disease , 2.53 ( 1.69 to 3.79 ) and 4.37 ( 1.84 to 10.42 ) for lung cancer , and 1.66 ( 1.07 to 2.59 ) and 1.65 ( 1.09 to 2.49 ) for stroke . Reduced FEV1 was also associated with an increased risk for each cause of death examined except cancer for lifelong nonsmokers . Conclusions : Impaired lung function is a major clinical indicator of mortality risk in men and women for a wide range of diseases . The use of FEV1 as part of any health assessment of middle aged patients should be considered . Smokers with reduced FEV1 should form a priority group for targeted advice to stop smoking . Key messages These increased risks , with the exception of the cancers , are apparent for lifelong non-smokers FEV1 is second in importance to cigarette smoking as a predictor of subsequent all cause mortality and is as important as cholesterol in predicting mortality from ischaemic heart disease FEV1 should be included in health assessment of middle aged men and women Smokers with a reduced FEV1 should be targeted with advice to stop BACKGROUND Data from multiple clinical , epidemiologic , and in vitro studies are conflicting regarding the effect of estrogen replacement therapy ( ERT ) on airway function in postmenopausal women with asthma . OBJECTIVE To determine the impact of withdrawal of estrogen administration in postmenopausal , asthmatic women . METHODS Twenty asthmatic women who were postmenopausal for at least 2 years and undergoing ERT were recruited for this prospect i ve crossover study . Subjects continued taking baseline estrogen for 28 days , stopped taking estrogen for 28 days , and then resumed taking the medication for 14 days . Objective measurements were obtained by recording daily peak flows in the morning and evening and formal spirometry at days 14 , 28 , 42 , 56 , and 70 . Compliance was measured by evaluating serum estradiol levels at days 28 and 56 . Daily use of short-acting beta-agonist bronchodilators was also recorded . RESULTS Differences in estradiol levels indicated compliance with the medication regimen . The combined day 14 and 28 ( taking estrogen ) mean percent predicted forced expiratory volume in 1 second ( FEV(1 ) ) was 77 % compared with the combined day 42 and 56 ( not taking estrogen ) mean FEV(1 ) of 78 % and the day 70 ( taking estrogen again ) FEV(1 ) of 76 % ( P>.05 ) . Average peak flow measurements were 295.5 L/min for the duration of ERT , 293.9 L/min while not undergoing ERT , and 291.8 L/min when ERT was restarted for the final 2 weeks of the study ( P>.05 ) . Use of short-acting beta-agonist bronchodilators did not differ between study periods . CONCLUSION These data indicate that neither the discontinuation nor reinitiation of ERT in postmenopausal , asthmatic women has any effect on objective measures of airway obstruction OBJECTIVE To investigate the effects of hormone therapy ( HT ) administered to postmenopausal women on pulmonary function tests ( PFT ) . METHODS Eighty-two postmenopausal women who were having natural or surgically initiated menopause and had no risk factor that could affect the respiratory system were included into this prospect i ve , r and omized study . Twenty-five women who refused to use HT were assessed as the control group ( Group I ) . Nineteen women who accepted using HT and who were having surgically initiated menopause were given continuous estrogen ( Group II ) , 23 were given continuous estrogen and progesterone in combination ( Group III ) and 15 were given cyclic estrogen and progesterone combination ( Group IV ) . Forced expiratory volume ( FEV1 ) , forced vital capacity ( FVC ) , FEV1/FVC , forced expiratory flow rate over 25 - 75 % of the forced vital capacity volume and peak expiratory flow rate were assessed at the beginning of the treatment and in the third month in order to evaluate the effects of HT regimens on the women 's PFT . RESULTS A statistically significant increase was observed only in the FEV1 and FVC parameters of Group III after three months of therapy ( P<0.05 ) . The comparison between pre- and posttherapy FEV1 and FVC values showed an increase in the Group IV , but the difference was not statistically significant , while there was no difference between basal and third month FEV1 and FVC values of the group receiving estrogen only . CONCLUSIONS It was seen that particularly continuous combined HT regimen positively affected the FEV1 and FVC parameters of the postmenopausal women Background Many chronic diseases are characterised by low- grade systemic inflammation . Oestrogens may promote immune response consistent with sex-specific patterns of diseases . In vitro culture and animal experiments suggest oestrogens are anti-inflammatory and might thereby protect against low- grade systemic inflammation . Evidence from epidemiological studies is limited . Using a Mendelian r and omisation analysis with a separate- sample instrumental variable ( SSIV ) estimator , we examined the association of genetically predicted 17β-estradiol with well-established systemic inflammatory markers ( total white cell count , granulocyte and lymphocyte count ) . Methods A genetic score predicting 17β-estradiol was developed in 237 young Chinese women ( university students ) from Hong Kong based on a parsimonious set of genetic polymorphisms ( ESR1 ( rs2175898 ) and CYP19A1 ( rs1008805 ) ) . Multivariable linear regression was used to examine the association of genetically predicted 17β-estradiol with systemic inflammatory markers among 3096 older ( 50 + years ) Chinese women from the Guangzhou Biobank Cohort Study . Results Predicted 17β-estradiol was negatively associated with white blood cell count ( −6.3 103/mL , 95 % CI −11.4 to −1.3 ) and granulocyte count ( −4.5 103/mL , 95 % CI −8.5 to −0.4 ) but not lymphocyte count ( −1.5 103/mL , 95 % CI −3.4 to 0.4 ) adjusted for age only . Results were similar further adjusted for education , smoking , use of alcohol , physical activity , Body Mass Index , waist-hip ratio , age of menarche , age at menopause , use of hormonal contraceptives and hormone replacement therapy . Conclusions Endogenous genetically predicted 17β-estradiol reduced low- grade systemic inflammatory markers ( white blood cell count and granulocyte count ) , consistent with experimental and ecological evidence of 17β-estradiol promoting immune response . Replication in a larger sample is required Rationale : Menopause is associated with changes in sex hormones , which affect immunity , inflammation , and osteoporosis and may impair lung function . Lung function decline has not previously been investigated in relation to menopause . Objectives : To study whether lung function decline , assessed by FVC and FEV1 , is accelerated in women who undergo menopause . Methods : The population ‐based longitudinal European Community Respiratory Health Survey provided serum sample s , spirometry , and question naire data about respiratory and reproductive health from three study waves ( n = 1,438 ) . We measured follicle‐stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis . Associations with lung function decline were investigated using linear mixed effects models , adjusting for age , height , weight , pack‐years , current smoking , age at completed full‐time education , spirometer , and including study center as r and om effect . Measurements and Main Results : Menopausal status was associated with accelerated lung function decline . The adjusted mean FVC decline was increased by −10.2 ml/yr ( 95 % confidence interval [ CI ] , −13.1 to −7.2 ) in transitional women and −12.5 ml/yr ( 95 % CI , −16.2 to −8.9 ) in post‐menopausal women , compared with women menstruating regularly . The adjusted mean FEV1 decline increased by −3.8 ml/yr ( 95 % CI , −6.3 to −2.9 ) in transitional women and −5.2 ml/yr ( 95 % CI , −8.3 to −2.0 ) in post‐menopausal women . Conclusions : Lung function declined more rapidly among transitional and post‐menopausal women , in particular for FVC , beyond the expected age change . Clinicians should be aware that respiratory health often deteriorates during reproductive aging |
12,416 | 29,621,757 | Discussion : Studies conducted with palatal models showed caries progression rates 2–5 times higher than the estimated clinical progression rates . | In situ caries research serves as a bridge between clinical research and laboratory studies .
In this kind of research , volunteers wear a removable intraoral splint or prosthesis containing research sample s. Many different in situ models exist to investigate secondary caries .
This systematic review compared currently existing secondary caries models and their lesion progression per day values . | The aims of this study were : ( 1 ) to correlate surface ( SH ) and cross-sectional hardness ( CSH ) with microradiographic parameters of artificial enamel lesions ; ( 2 ) to compare lesions prepared by different protocol s. Fifty bovine enamel specimens were allocated by stratified r and omisation according to their initial SH values to five groups and lesions produced by different methods : MC gel ( methylcellulose gel/lactic acid , pH 4.6 , 14 days ) ; PA gel ( polyacrylic acid/lactic acid/hydroxyapatite , pH 4.8 , 16 h ) ; MHDP ( undersaturated lactate buffer/methyl diphosphonate , pH 5.0 , 6 days ) ; buffer ( undersaturated acetate buffer/fluoride , pH 5.0 , 16 h ) , and pH cycling ( 7 days ) . SH of the lesions ( SH1 ) was measured . The specimens were longitudinally sectioned and transverse microradiography ( TMR ) and CSH measured at 10- to 220-μm depth from the surface . Overall , there was a medium correlation but non-linear and variable relationship between mineral content and √CSH . √SH1 was weakly to moderately correlated with surface layer properties , weakly correlated with lesion depth but uncorrelated with integrated mineral loss . MHDP lesions showed the highest subsurface mineral loss , followed by pH cycling , buffer , PA gel and MC gel lesions . The conclusions were : ( 1 ) CSH , as an alternative to TMR , does not estimate mineral content very accurately , but gives information about mechanical properties of lesions ; ( 2 ) SH should not be used to analyse lesions ; ( 3 ) artificial caries lesions produced by the protocol s differ , especially considering the method of analysis This paper describes a microradiographic method for measuring mineral concentration in a transversal geometry with thick ( ≤3.2 mm ) sections : transversal wavelength-independent microradiography ( T-WIM ) . It was tested on bovine enamel and dentin sample s in vitro , and the results were vali date d with those of transversal microradiography ( TMR ) . 48 enamel and 48 dentin sample s ( 3.2 × 3.2 × 1.5 mm ) were embedded in acrylic resin , r and omly divided into six groups of 8 dentin or 8 enamel sample s , and demineralized for 0 ( sound control ) , 1 , 2 , 3 , 4 , or 5 weeks . For T-WIM , sample s were imaged on film with polychromatic 40-kV Cu X-rays with an Al ( 0.25 mm)/Ni ( 0.02 mm ) filter together with an aluminium/zinc step wedge . TMR slices ( about 80 µm for enamel and about 130 µm for dentine ) were subsequently cut from the centre of the sample s and subjected to TMR . Microradiographs from both methods were digitized and image analysis software was used to calculate lesion depth and mineral loss . The relations between T-WIM and TMR results for mineral loss ( ΔZ ) and lesion depth were nearly linear ( r ≧ 0.96 ) for both enamel and dentin . The slopes of the regression lines were between 0.99 and 1.02 except for ΔZ in dentine , which was 0.89 . It was concluded that T-WIM is a suitable method for TMR on thick sample PURPOSE To evaluate the in situ effect of fluoride and MDPB-containing adhesives on antibacterial activity around restorations in conditions of high caries risk . METHODS Bovine enamel and dentin blocks were restored with a fluoride-containing ( One-up Bond F Plus - OP ) or a MDPB and fluoride-containing adhesive ( Clearfil Protect Bond - PB ) . Volunteers ( n = 17 ) wore an intra-oral appliance containing three enamel and three dentin blocks , aligned side-by-side and restored with OP or PB and one enamel and dentin block ( controls ) . The cariogenic challenge was carried out in two phases of 14 days each . The counts of total streptococci ( TM ) , mutans streptococci ( MS ) and lactobacilli ( LB ) were analyzed in the biofilm formed . Cross-sectional microhardness ( CSM ) and polarized light microscopy ( PLM ) evaluated caries lesions around the restorations and the demineralization extension . Data obtained by CSM testing was analyzed by Split-Split Plot ANOVA ( P < 0.05 ) . PLM and microbiota results were analyzed by Wilcoxon test ( P < 0.05 ) . RESULTS TM and MS counts were highest for the OP enamel restorations , and these presented higher lesion depths than PB in both the enamel and dentin . The CSM in dentin was the lowest at 60 μm from the restoration wall . None of the adhesives prevented demineralization and bacteria growth , but PB reduced the amount of oral pathogens in enamel and demineralization around restorations in enamel and dentin This study evaluates in situ the effect of erbium-doped yttrium aluminum garnet ( Er : YAG ) laser parameters on the development of caries-like lesions adjacent to dental restorations . One hundred fifty bovine enamel slabs were r and omly allocated among 15 volunteers . The specimens were subdivided into ten groups : nine experimental groups prepared with Er : YAG laser ( 300 mJ output , frequency of 2 , 4 or 6 Hz , water flow rate of 2.0 , 5.0 , or 8.0 mL/min ) and one control group ( high-speed h and piece ) . The prepared cavity was restored with a composite resin , and the slabs were mounted on palatal appliance to be installed in the volunteers to the cariogenic challenge . After this , the specimens were sectioned to the longitudinal microhardness measurements . Data were su bmi tted to Friedman and Wilcoxon paired tests . All groups prepared with Er : YAG laser demonstrated microhardness values higher than those prepared with high-speed h and piece , which showed the lowest microhardness values ( 24.86 ) . The group prepared with Er : YAG laser ( 2 Hz–2.0 mL/min ) showed the highest microhardness values ( 152.43 ) , followed by those prepared with Er : YAG laser ( 2 Hz–5.0 mL/min ) ( 133.08 ) and Er : YAG laser ( 2 Hz–8.0 mL/min ) ( 91.61 ) , respectively . The groups Er : YAG laser with 4 and 6 Hz of frequency and water flow rates of 2.0 , 5.0 , and 8.0 mL/min showed microhardness values lower than the groups cited above and showed statistical similarity among them . The Er : YAG laser parameters employed to cavity preparation influenced the acid resistance of the irradiated substrate , and the Er : YAG laser was capable to control the development of caries-like lesions around composite resin restorations PURPOSE To investigate in situ the influence of gaps in the development of secondary caries lesion in adhesive restorations . METHODS 10 volunteers utilized intra-oral appliances , containing three human dental blocks ( enamel and dentin ) , representing the three different groups ( two restored , one sound ) : ( 1 ) restored with resin composite using the total acid etch adhesive technique ( 37 % H3PO4 + Single Bond + Z250 ) ; ( 2 ) restored with resin composite but without acid etching ( Single Bond + Z250 ) ; ( 3 ) and sound blocks ( control group ) . The dental blocks ( n=30 ) were r and omly positioned inside the intra-oral appliances , and covered by a porous tissue ( gabardine base ) to induce a cariogenic biofilm . The volunteers used the appliances 24 hours daily for a 28-day period , removing just during meals and oral hygiene . Eight times a day , a 20 % sucrose solution was dripped onto the blocks . Five minutes later , the appliance was washed with distilled water and replaced in the oral environment . After the experimental period , the dental blocks were removed from the appliance and examined by visual examination to detect the presence or the absence of an active carious lesion ( kappa= 0.89 ) . Posteriorly , they were prepared for the polarized light microscopy examination , which was performed to describe enamel surface characteristics on the restored and unrestored blocks with active caries lesion ( kappa= 1 ) . RESULTS The visual examination demonstrated that almost all ( 29/30 ) of the blocks showed non-cavitated active caries lesion on the enamel surface . The microscopic evaluation showed non-cavitated caries lesions on enamel surfaces for all groups . In the restored blocks ( with and without the total etch technique ) , the demineralization was first identified as an outer lesion that follows the enamel prism directions , and in some cases , reached the cavity walls . The results showed that caries lesion development adjacent to the restoration was determined by the cariogenic challenge of the oral environment , instead of the restoration adhesive quality , and the wall lesion was determined by the prism orientation , regardless of the presence of gaps OBJECTIVE This study assessed the effect of the Er : YAG laser on enamel adjacent to restorations su bmi tted to cariogenic challenge in situ , by microhardness analysis . BACKGROUND DATA The influence of Er : YAG laser energy on secondary caries formation has been investigated in vitro . However , no research involving demineralization around cavities prepared with the Er : YAG laser under intra-oral conditions has yet been described . MATERIAL S AND METHODS Slabs of enamel were r and omly assigned to seven groups ( n = 12 ) , according to the cavity preparation technique : groups I , II , and III -- Er : YAG laser , 250 mJ , at 2 , 3 , and 4 Hz , respectively ; groups IV , V , and VI--350 mJ , at 2 , 3 , and 4 Hz , respectively ; group VII -- high-speed h and piece ( control ) . Cavities were restored and the specimens were fixed in intra-oral appliances and worn by 12 volunteers for 14 d. Sucrose solution was applied to each slab 6 times/d . Sample s were removed , sectioned , and examined for microhardness at 100 , 200 , and 300 microm ( factor distance ) , and 30 , 60 , and 90 microm ( factor depth ) , from the restoration and enamel surface , respectively . RESULTS Analysis of variance according to a split-plot model showed no difference among the cavity preparation techniques , among distances , or among depths , as well as no difference in the interaction between the factors of cavity preparation and distance . A significant difference was found in the interaction of cavity preparation and depth ( p < 0.0001 ) , as identified by contrast technique . CONCLUSION The results revealed that the Er : YAG laser did not differ from conventional cavity preparation with regard to enamel microhardness AIM This in situ study assessed the effects of adhesive systems containing or not fluoride and /or the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide ( MDPB ) on the microbiological composition of dental biofilm and enamel demineralization . MATERIAL S AND METHODS During two phases of 14 days , ten volunteers wore intraoral palatal appliances containing two slabs of human enamel according to a double-blind , crossover design . The slabs were r and omly restored using a composite resin and one of the following adhesive systems : All-Bond SE(TM ) ( self-etch , fluoride/MDPB free adhesive , AB ) and Clearfl Protect Bond ( self-etch containing fluoride and MDPB adhesive , CB ) . The biofilm formed on the slabs was analyzed with regard to total and mutans streptococci and lactobacilli counts . Demineralization represented by integrated area of hardness × lesion depth Delta S ( ΔS ) was determined on enamel by analysis of cross-sectional microhardness , at 20 and 70 μm from the restoration margin . Data were analyzed by ANOVA . RESULTS No statistically significant difference was found either in enamel demineralization or in the microbiological composition of dental biofilm . CONCLUSION All adhesive systems containing or not fluoride and /or MDPB tested were unable to inhibit secondary caries in the in situ model used in the present research OBJECTIVES Since secondary caries is one of the main reasons for replacing restorations , this study assessed the effects of different restorative material s on the microbiological composition of dental biofilm and on enamel demineralisation around the restoration . METHODS A r and omized , double-blind , split-mouth in situ design was conducted in one phase of 14 days , during which , 20 volunteers wore palatal devices containing five human dental enamel slabs . Each slab was r and omly restored with one of the following material s : Filtek-Z-250/Single Bond , control group ( composite resin ) , Permite ( amalgam ) , Fuji II ( encapsulated resin-modified glass ionomer ) , Vitremer ( resin-modified glass ionomer ) and Ketac Molar ( conventional glass ionomer ) . The volunteers used fluoride dentifrice , 3x/day and a 20 % sucrose solution was dripped onto the slabs 8x/day . The biofilm formed on the slabs was analyzed to determine the counts of total streptococci , mutans streptococci and lactobacilli . Enamel demineralisation was determined by cross-sectional microhardness ( CSMH ) at 20 and 70 microm from the margin of the restoration . Kruskal-Wallis and analysis of variance , followed by least mean squares ( LMS ) test , were used to evaluate microbiota and CSMH among the groups . The significance level used was 5 % . RESULTS No statistically significant differences were found in the cariogenic microbiota grown on the slabs . At a 20-mum distance , only Fuji II statistically differed from the other groups , showing the lowest demineralisation . At 70 microm , Fuji II significantly inhibited demineralisation when compared to Permite , Filtek-Z-250 and Ketac Molar . CONCLUSIONS In the context of fluoride dentifrice and under the cariogenic exposure conditions of this study , only the encapsulated resin-modified glass ionomer material provided additional protection against secondary caries The purpose of this study was to compare the amount of fluoride in plaque formed on glass ionomer cement or composite and to evaluate the effects of fluoride released on growth of cariogenic microflora , fluoride uptake , and secondary caries formation under in situ conditions of a high cariogenic challenge . Ten adult volunteers took part in this crossover study performed in two phases of 28 days . Eighty enamel blocks were r and omly restored with glass ionomer cement ( Chelon-Fil-Espe ) or composite ( Silux ) . During each phase of the study , an acrylic resin appliance , containing four enamel blocks restored with the same material , was constructed for each of the volunteers . During the experimental period , all subjects used fluoride-free dentifrice , refrained from brushing the restored enamel blocks , and immersed the appliances into 20 % sucrose solution eight times a day . Fluoride levels , mutans streptococci , and lactobacilli were assessed in dental plaque . Fluoride uptake and microhardness profiles were determined in enamel around the restorations . Statistical analyses indicated a significantly higher level of fluoride ( p < 0.05 ) and a lower level of mutans streptococci plaque formed on glass ionomer cement . Analysis of variance in a split-plot model indicated that in the enamel around the glass ionomer restoration the fluoride uptake was significantly greater ( p < 0.025 ) and the mineral loss significantly lower ( p < 0.01 ) . The results show that glass ionomer cement presents a broad anticariogenic effect and may be of value in preventing secondary caries , even under conditions of a high caries risk There is no consensus about an association between microleakage and secondary caries , especially considering the presence of fluoride ( F ) at the tooth/restoration interface . Thus , a r and omized , double-blind , crossover study was carried out to evaluate in situ the effect of microleakage on caries around enamel-dentine restorations in the presence of F from dental material s or dentifrice , either alone or in combination . In 4 phases of 14 days each , 14 volunteers wore palatal devices containing dental slabs restored with composite resin ( CR ) or resin-modified glass ionomer cement ( GI ) . Restorations were made without leakage ( L– ) , following the recommended adhesive procedures , or with leakage ( L+ ) , in the absence of adhesive procedures . Plaque-like biofilm ( PLB ) was left to accumulate on the restored slabs , which were exposed extraorally to a 20 % sucrose solution 10 × /day . The volunteers used a non-F ( NF ) or an F ( FD ) dentifrice 3 × /day , depending on the experimental phase . No differences were found between L+ or L– restorations ( p > 0.05 ) . Higher demineralization in both enamel and dentine around CR restorations was observed under NF ( p < 0.05 ) . F concentration was higher in the fluid of PLB exposed to FD or formed onto GI restoration ( p < 0.05 ) . These results suggest that while microleakage does not affect caries development , GI or FD may maintain increased F levels in the PLB , thereby decreasing caries progression OBJECTIVE As resin-modified glass-ionomer cement ( RMGIC ) is an adhesive material , its association to dentin bonding agents ( DBAs ) was previously proposed . This study investigated the adjunctive behavior of an RMGIC with etch- and -rinse bonding systems under in situ/ex vivo cariogenic challenge . METHOD AND MATERIAL S Bovine enamel blocks ( 3 3 3 3 2 mm ) were r and omly assigned to group VP , Vitremer + its own primer ( 3 M ESPE ) ; group VSB , Vitremer + Single Bond ( 3 M ESPE ) ; and group VPB , Vitremer + Prime and Bond 2.1 ( Dentsply ) . Two blocks of each group were r and omly placed in an acrylic palatal appliance , so each appliance included six blocks . Volunteers ( n = 10 ) wore these appliances according to given instructions to promote a sucrose challenge eight times/day for 15 days . After this period , the blocks were removed from the devices and cleaned , and demineralization was assessed through longitudinal microhardness analysis ( Knoop indenter , 25 g/5 s ) . Data were su bmi tted to three-way ANOVA and Tukey test ( P < .05 ) . RESULTS No treatment was able to completely avoid demineralization . All material s showed a statistically significant difference in mineral loss when the microhardness on the outer enamel was compared with deeper regions ( P < .05 ) . CONCLUSION Association of the tested RMGICs with etch- and -rinse DBAs did not seem to be more beneficial against caries than the conventional treatment with RMGIC The usefulness of fluoride-releasing restorations in secondary caries prevention may be question ed because of the presence of other common sources of fluoride and because of ageing of the restorations . This study tested the hypothesis that glass-ionomer cement restorations , either aged or unaged , do not prevent secondary root caries , when fluoride dentifrice is frequently used . Sixteen volunteers wore palatal appliances in two phases of 14 days , according to a 2 × 2 crossover design . In each phase the appliance was loaded with bovine root dentine slabs restored with either glass-ionomer or resin composite , either aged or unaged . Specimens were exposed to cariogenic challenge 4 times/day and to fluori date d dentifrice 3 times/day . The fluoride content in the biofilm ( FB ) formed on slabs and the mineral loss ( ΔZ ) around the restorations were analysed . No differences were found between restorative material s regarding the FB and the ΔZ , for either aged ( p = 0.792 and p = 0.645 , respectively ) or unaged ( p = 1.00 and p = 0.278 , respectively ) groups . Under the cariogenic and fluoride dentifrice exposure conditions of this study , the glass-ionomer restoration , either aged or unaged , did not provide additional protection against secondary root caries The aim of this study was to evaluate the resin-dentin bonds of two simplified etch- and -rinse adhesive after simulated cariogenic and inhibited cariogenic challenge in situ . Dental cavities ( 4 mm wide , 4 mm long , and 1.5 mm deep ) were prepared in 60 bovine teeth with enamel margins . Restorations were bonded with either adhesive Adper Single Bond 2 ( 3MESPE ) or Optibond Solo Plus ( Kerr ) . Forty restorations were included in an intra-oral palatal appliance that was used for 10 adult volunteers while the remaining 20 dental blocks were not su bmi tted to any cariogenic challenge [ NC group ] and tested immediately . For the simulated cariogenic challenge [ C+DA ] , each volunteer dropped 20 % sucrose solution onto all blocks four times a day during 14 days and distilled water twice a day . In the inhibited cariogenic challenge group [ C + FA ] , the same procedure was done , but slurry of fluoride dentifrice ( 1.100 ppm ) was applied instead of water . The restored bovine blocks were sectioned to obtain a slice for cross-sectional Vickers microhardness evaluation and resin-dentin bonded sticks ( 0.8 mm(2 ) ) for resin-dentin microtensile evaluation . Data were evaluated by two-way ANOVA and Tukey 's tests ( α = 0.05 ) . Statistically lower microhardness values and degradation of the resin-dentin bonds were only found in the C + DW group for both adhesives . The in situ model seems to be a suitable short-term methodology to investigate the degradation of the resin-dentin bonds under a more realistic condition This study compared the tubular dimensions and distribution of human and bovine dentin . Ten human molars and 10 bovine incisors were ground with a high-speed h and piece to obtain 3 sections at different dentin depths ( superficial , middle and deep ) . The specimens were sputter-coated with gold to be examined under scanning electron microscopy ( SEM ) . Three SEM micrographs were recorded r and omly for each dentin depth . The number of tubules was counted and the diameter of 5 tubules selected at r and om was measured in each SEM micrograph . Data were analyzed statistically by ANOVA and Tukey 's test ( alpha=0.05 ) . In bovine teeth , superficial dentin ( 4.21 microm ) and middle dentin ( 3.98 microm ) had a significantly greater ( p<0.05 ) diameter than deep dentin ( 3.14 microm ) tubules . In human teeth , superficial dentin tubule diameter ( 2.42 microm ) was significantly smaller ( p<0.05 ) than deep dentin ( 2.99 microm ) and middle dentin ( 2.94 microm ) tubule diameters , which did not differ significantly from each other ( p>0.05 ) . The number of tubules per square millimeter , regardless of the region , was significantly greater in human dentin ( 22,329 ) than in bovine dentin ( 15,964 ) . There was a clear difference in tubule structure and morphology between human and bovine dentin BACKGROUND Failure of dental restorations is a major concern in dental practice . Replacement of failed restorations constitutes the majority of operative work . Clinicians should be aware of the longevity of , and likely reasons for the failure of , direct posterior restorations . In a long-term , r and omized clinical trial , the authors compared the longevity of amalgam and composite . SUBJECTS , METHODS AND MATERIAL S : The authors r and omly assigned one-half of the 472 subjects , whose age ranged from 8 through 12 years , to receive amalgam restorations in posterior teeth and the other one-half to receive resin-based composite restorations . Study dentists saw subjects annually to conduct follow-up oral examinations and take bitewing radiographs . Restorations needing replacement were failures . The dentists recorded differential reasons for restoration failure . RESULTS Subjects received a total of 1,748 restorations at baseline , which the authors followed for up to seven years . Overall , 10.1 percent of the baseline restorations failed . The survival rate of the amalgam restorations was 94.4 percent ; that of composite restorations was 85.5 percent . Annual failure rates ranged from 0.16 to 2.83 percent for amalgam restorations and from 0.94 to 9.43 percent for composite restorations . Secondary caries was the main reason for failure in both material s. Risk of secondary caries was 3.5 times greater in the composite group . CONCLUSION Amalgam restorations performed better than did composite restorations . The difference in performance was accentuated in large restorations and in those with more than three surfaces involved . CLINICAL IMPLICATION S Use of amalgam appears to be preferable to use of composites in multisurface restorations of large posterior teeth if longevity is the primary criterion in material selection BACKGROUND AND OBJECTIVES Er : YAG laser has been used for caries removal and cavity preparation , using ablative parameters . Its effect on the margins of restorations su bmi tted to cariogenic challenge has not yet been sufficiently investigated . The aim of this study was to assess the enamel adjacent to restored Er : YAG laser-prepared cavities su bmi tted to cariogenic challenge in situ , under polarized light microscopy . STUDY DESIGN / MATERIAL S AND METHODS Ninety-one enamel slabs were r and omly assigned to seven groups ( n = 13 ) : I , II , III-Er : YAG laser with 250 mJ , 62.5 J/cm2 , combined with 2 , 3 , and 4 Hz , respectively ; IV , V , VI-Er : YAG laser with 350 mJ , 87.5 J/cm(2 ) , combined with 2 , 3 , and 4 Hz , respectively ; VII-High-speed h and piece ( control ) . Cavities were restored and the restorations were polished . The slabs were fixed to intra-oral appliances , worn by 13 volunteers for 14 days . Sucrose solution was applied to each slab six times per day . Sample s were removed , cleaned , sectioned and ground to polarized light microscopic analysis . Demineralized area and inhibition zone width were quantitatively assessed . Presence or absence of cracks was also analyzed . Scores for demineralization and inhibition zone were determined . RESULTS No difference was found among the groups with regard to demineralized area , inhibition zone width , presence or absence of cracks , and demineralization score . Inhibition zone score showed difference among the groups . There was a correlation between the quantitative measures and the scores . CONCLUSION Er : YAG laser was similar to high-speed h and piece , with regard to alterations in enamel adjacent to restorations su bmi tted to cariogenic challenge in situ . The inhibition zone score might suggest less demineralization at the restoration margin of the irradiated substrates . Correlation between the quantitative measures and scores indicates that score was , in this case , a suitable complementary method for assessment of caries lesion around restorations , under polarized light microscopy PURPOSE To evaluate in situ the anticariogenic effect of fluoride and MDPB containing adhesive systems at the restoration interface , by microhardness tests . METHODS 120 fragments containing preparations for resin composite restorations performed at the cemento-enamel junction were r and omly distributed among the adhesive systems to be tested . The adhesive systems were applied in accordance with the manufacturers ' instructions : Optibond FL , Adper Single Bond 2 , Prime & Bond 2.1 , Optibond Solo Plus , Adper Prompt , Clearfil Protect Bond and restored with the nanoparticulate resin composite Z350 . Twenty volunteers used a palatal appliance containing fragments restored with each adhesive system for 21 days , and applied 20 % sucrose on them eight times a day to simulate a high cariogenic challenge . Microhardness tests were performed at different depths ( 20 microm , 40 microm and 60 microm from the occlusal margin of the restoration ) and at different distances ( 100 microm , 200 microm and 300 microm from the adhesive interface ) . RESULTS ANOVA showed that for enamel , there was significant difference between the adhesive systems ( P=0.0106 ) ; the interaction adhesive system*distance was a significant ( P=0.0006 ) , and the one-step self-etching adhesive system containing fluoride ( Adper Prompt ) presented a higher anticariogenic effect . However , for dentin , the adhesive system used did not interfere in decreasing the severity of caries formation |
12,417 | 12,137,678 | REVIEW ER 'S CONCLUSIONS The sponge was less effective than the diaphragm in preventing pregnancy .
Discontinuation rates were higher at 12 months as well . | BACKGROUND The contraceptive vaginal sponge was developed as an alternative to the contraceptive diaphragm .
The sponge , made of polyurethane impregnated with nonoxynol-9 ( 1 g ) , releases 125 mg of the spermicide over 24 h of use .
Unlike the diaphragm , the sponge can be used for more than one coital act within 24 h without the insertion of additional spermicide , and the sponge does not require fitting or a prescription from a physician .
How the sponge compares with the diaphragm in terms of efficacy and continuation is not clear .
OBJECTIVES To compare the efficacy and continuation rates of the sponge compared with the diaphragm ( used with nonoxynol-9 as a spermicide ) .
Our a priori hypothesis was that the sponge would have a higher failure rate and higher discontinuation rates than the diaphragm . | The actual effectiveness rates of natural and barrier methods of family planning are lower than the theoretical ones . If couples accurately defined the limits of the fertile phase and used barriers at that time , then actual effectiveness might increase . A r and omized , controlled clinical trial was initiated to determine the effectiveness of the contraceptive sponge used only during the fertile time and to compare this with sponge use at every intercourse . Recruitment problems and discontinuation forced the early termination of this study , but qualitative information about compliance and acceptability was collected . Common sponge problems were reported as were misuses of the sponge , but problems and misuse were not related . Determination of the fertile phase was reportedly easy , but complaints of and discontinuation for inconvenience occurred . For unplanned pregnancies , contraceptive behaviors around the time of conception are presented The results of a r and omized United States study indicated that the Today contraceptive sponge was less effective than the diaphragm ( 1-year cumulative life-table rate of 17.4 versus 12.9 pregnancies per 100 women , p = 0.01 ) . However , this overall comparison is misleading . Using univariate and multivariate analyses to account for the effects of user characteristics we found parity to be the most important single determinant of effectiveness for users of the sponge , but parity was unimportant as a risk factor for pregnancy among diaphragm users . For nulliparous women the sponge was as effective as a physician-prescribed barrier method ( 13.9 for sponge , 12.8 for diaphragm , p = 0.45 ) ; however , parous women using the sponge were twice as likely to become pregnant ( 28.3 for sponge , 13.4 for diaphragm , p = 0.001 ) . The effect of parity among sponge users is consistent with the results of international studies of the contraceptive sponge Proper r and omisation means little if investigators can not include all r and omised participants in the primary analysis . Participants might ignore follow-up , leave town , or take aspartame when instructed to take aspirin . Exclusions before r and omisation do not bias the treatment comparison , but they can hurt generalisability . Eligibility criteria for a trial should be clear , specific , and applied before r and omisation . Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested . In principle , assessment of exclusions after r and omisation is simple : none are allowed . For the primary analysis , all participants enrolled should be included and analysed as part of the original group assigned ( an intent-to-treat analysis ) . In reality , however , losses frequently occur . Investigators should , therefore , commit adequate re sources to develop and implement procedures to maximise retention of participants . Moreover , research ers should provide clear , explicit information on the progress of all r and omised participants through the trial by use of , for instance , a trial profile . Investigators can also do secondary analyses on , for instance , per- protocol or as-treated participants . Such analyses should be described as secondary and non-r and omised comparisons . Mish and ling of exclusions causes serious method ological difficulties . Unfortunately , some explanations for mish and ling exclusions intuitively appeal to readers , disguising the seriousness of the issues . Creative mismanagement of exclusions can undermine trial validity To investigate the effect of the contraceptive sponge on the incidence of sexually transmitted diseases , we conducted a clinical trial among a high-risk population of women in Bangkok , Thail and . Two hundred fifty-five women were r and omly assigned either to use the sponge or not and were evaluated weekly for gonorrhea and chlamydial infection . After adjustment by logistic regression for potentially confounding factors , women using the sponge were less likely to have contracted chlamydial infection ( odds ratio [ OR ] , 0.6 ; 90 % confidence interval [ CI ] , 0.4 - 1.0 ) and gonorrhea ( OR , 0.9 ; CI , 0.6 - 1.3 ) as compared with women not using the sponge . These estimates probably underestimate the degree of protection because some exposure was misclassified in this pilot phase of the study . These results are consistent with other studies indicating that spermicides protect against gonorrhea and also demonstrating protection against an organism of even greater public health concern , Chlamydia trachomatis Objective : This study was undertaken to assess the efficacy , safety and acceptability of two different-dose regimens of the Protectaid ® contraceptive sponge . Methods : The toxic effects of two forms of the new vaginal contraceptive sponge , Protectaid ® , in the cervical and vaginal tissues were studied . Both types were impregnated with F-5 gel containing different doses of nonoxynol-9 ( NX9 ; 0.5 % and 0.125 % ) . The sponge was used by 35 women aged 20 - 35 years ( mean 28.7 years ) r and omly allocated into two groups ( Group A : 0.5 % NX9 , n = 20 ; Group B : 0.125 % NX9 , n = 15 ) . Results : During a 12-month period both regimens demonstrated a 91.4 % overall contraceptive efficacy . Colposcopic examinations showed no significant cervical or vaginal lesions in either group , except for two cases at the 2-week and 3-month examinations in Group A women . In the former , inflammatory changes of little clinical significance were seen and the colposcopic appearance of the vagina was non-specific . In this case , the focal lesions were accompanied by dilated capillaries ( hyperemia ) . In the second case , degenerative inflammatory changes , with the inflammatory foci varying in shape and distribution , were observed . Cervical cultures taken 6 months after the start of treatment showed the presence of Mycoplasma hominis and C and ida albicans in one and two cases , respectively , in Group A. In Group B , cervical cultures taken at 3 months showed Gardnerella vaginalis and β-hemolytic streptococci group B in one and two cases , respectively . Conclusion : The potent spermicidal and protective properties of this new contraceptive sponge may be of benefit to the sexually active female . Since the sponge was very well accepted by both the study participants and their sexual partners , it can be considered as a valuable barrier method A comparative trial was conducted in the United States to compare the Today contraceptive sponge and the diaphragm used with spermicide . Subjects were r and omly assigned to contraceptive methods and were followed up for 1 year . None of the subjects were previous sponge users , but about 30 % were previous diaphragm users . The overall cumulative 1-year life-table pregnancy rate was higher for sponge users compared to diaphragm users . No serious side effects occurred with either product . The discontinuation rates for allergic-type reactions and discomfort were higher for sponge users . Similar rates of method -related complaints and discontinuation rates for personal and product-related reasons suggest there were no differences in the acceptability of the two products . In this trial , the allowable use time for the sponge was 2 days . The sponge is now recommended for 1-day use . The overall results of the study indicate the sponge to be a safe and acceptable method of contraception with an effectiveness rate in the range of that for other vaginal contraceptives Users of the Today contraceptive sponge who participated in a comparative trial of the sponge and diaphragm were followed up for an additional year . There were no serious adverse effects attributable to sponge use during the second year of use . The second year life-table pregnancy rate for sponge users was significantly lower ( p<0.05 ) than the first year rate . The pregnancy rates for first time sponge and diaphragm users were similar ( p>0.10 ) and both rates improved with increasing user experience . ResuméLes utilisatrices d'éponges contraceptives Today qui ont participé à des essais destinés à faire une comparaison entre les éponges et les diaphragmes ont été suivies pendant une année supplémentaire . Aucun effet défavorable grave qui puisse être attribué à l'usage des éponges n'a été constaté au cours de la seconde année . Les taux de grossesses chez les utilisatrices d'éponges ont été significativement plus faibles ( p<0,05 ) pour la seconde année que pour la première ( calculé par la méthode des tables de survie ) . Les taux de grossesses étaient similaires chez celles qui utilisaient l'éponge et le diaphragme pour la première fois ( p>0,10 ) et ces taux se sont améliorés dans un cas comme dans l'autre à mesure que ces femmes en acquéraient l'expérience . ResumenA usuarias de la esponja anticonceptiva Today que participaron en una prueba comparativa de la esponja y el diafragma , se les hizo seguimiento durante un año adicional . Durante el segundo año de uso no se produjeron effectos adversos serios atribuibles a la esponja . Los embarazos que ocurrieron durante el segundo año de uso , analizados por la tabla de vida , fueron significativamente más bajos que los del primer año ( p<0.05 ) . Las tasas de embarazo para usuarias por primera vez de la esponja y del diafragma fueron similares ( p>0,10 ) y ambas tasas mejoraron con el aumento de experiencia en las usuarias This paper describes the results from a r and omized clinical trial comparing the Collatex vaginal contraceptive sponge ( a predecessor of the Today sponge ) and Neo Sampoon foaming vaginal contraceptive tablets ; the trial was conducted from 1979 to 1983 in four centers located in three countries ( two in Yugoslavia and one each in Taiwan and Bangladesh ) . The sponge was associated with more insertion and retention problems than the tablet , especially in the two Asian centers . More Neo Sampoon users complained of a burning or stinging sensation . This complaint , however , seemed to be well-tolerated and was not a frequent reason for irregular use and /or discontinuation of use of the tablets . Clinical ly significant medical complications were rarely reported for either method . Sponge users were more likely to report irregular use than tablet users , primarily due to inconvenience of use . Rates of discontinuation at six months of use were also consistently higher among sponge users than Neo Sampoon users in the four centers . Life-table pregnancy rates at 12 months of use ranged from 3.8 to 18.2 per 100 sponge users and 6.2 to 29.9 per 100 Neo Sampoon users , based on data from the two Yugoslavian centers and the Taiwan center ( data from the Bangladesh center were excluded from analysis of pregnancy rates ) . Practical implication s of these findings are discussed Neo Sampoon , a foaming vaginal tablet containing 60 mg of the spermicide menfegol , and the Collatex sponge ( now marketed in the United States as the Today sponge ) , a domeshaped polyurethane device that contains 1 g of nonoxynol-9 , were compared in terms of effectiveness , safety , and acceptability . Both methods were new to the Maribor General Hospital , Yugoslavia , where the trial was conducted among 450 volunteers r and omly assigned to one of the two methods . At 12 months , the life-table pregnancy rate per 100 women for the Neo Sampoon group was 12.8 , compared with a rate of 10.4 among the sponge users ( P>.10 ) . After pregnancy , the second most frequent reason for termination was discomfort , with a 12-month termination rate due to this cause of 6.9 per 100 women in the Neo Sampoon group and 6.2 in the sponge group . Although fewer than a quarter of the volunteers had any experience with barrier methods before this trial , the life-table continuation rate was high in both groups , with more than 70 % using their assigned method for the full 12 months . Also , upon conclusion of the study , 41 % of the volunteers chose another barrier contraceptive method . Although the effectiveness of the sponge and Neo Sampoon is not comparable to that of the pill or IUD , both vaginal methods appear to be safe and acceptable additions to the range of contraceptive choices To investigate the effect of the nonoxynol 9-impregnated contraceptive sponge on the incidence of chlamydial infection , gonorrhea , and c and idiasis , we conducted a r and omized comparative study among high-risk women in Bangkok , Thail and . The first ( parallel ) portion of the study covered 434 woman-weeks among sponge users and 494 woman-weeks among nonusers . As compared with women not using the sponge , sponge users were found to be less likely to become infected with chlamydia ( relative rate , 0.67 ; 95 % confidence interval , 0.42 to 1.07 ) and gonorrhea ( relative rate , 0.31 [ 0.16 to 0.60 ] ) but more likely to become infected with C and ida ( relative rate , 2.76 [ 0.96 to 7.98 ] ) . Women who continued in the study were crossed over to the alternate group , with former nonusers starting to employ the sponge and vice versa . The results of this second phase were similar to those of the larger parallel study . Overall , these results suggest that women using the sponge are protected against the two most common sexually transmitted pathogens , which are also those with the most serious health consequences . However , women using the sponge should be advised they may have an increased likelihood of a vaginal infection with C and ida CONTEXT Nonoxynol-9 has been suggested as a vaginal microbicide to protect against common sexually transmitted infections . OBJECTIVE To compare nonoxynol-9 gel and condom use ( gel group ) vs condom use alone ( condom group ) for the prevention of male-to-female transmission of urogenital gonococcal and chlamydial infection . DESIGN AND SETTING R and omized controlled trial conducted at 10 community clinics and 10 pharmacies in Yaoundé , Cameroon , between October 1998 and September 2000 , with 6 months of follow-up . PARTICIPANTS High-risk population of 1251 women ( excluding sex workers ) being treated for or who had symptoms of sexually transmitted infections . Three were excluded from the gel group ( 0.5 % ) and 7 from the condom group ( 1 % ) because of no follow-up data . INTERVENTIONS Nonoxynol-9 gel ( 100 mg ) and condoms or condoms only . MAIN OUTCOME MEASURE A positive test result for gonococcal or chlamydial infection by the ligase chain reaction assay ; secondary outcome measure was a positive test result for human immunodeficiency virus ( HIV ) . RESULTS The rate ratio ( RR ) for new urogenital infections was 1.2 for the gel group vs condom group ( 95 % confidence interval [ CI ] , 0.9 - 1.6 ; P = .21 ) . The gel group had 116 diagnosed gonococcal infections , chlamydial infections , or both for a rate of 43.6 per 100 person-years , and the condom group had 100 infections for a rate of 36.6 per 100 person-years . The RR for gonococcal infection in the gel group vs the condom group was 1.5 ( 95 % CI , 1.0 - 2.3 ) and for chlamydial infection was 1.0 ( 95 % CI , 0.7 - 1.4 ) . There were 5 new cases of HIV infections in the gel group and 4 in the condom group . Three women in each group became pregnant during the study . CONCLUSION Nonoxynol-9 gel did not protect against urogenital gonococcal or chlamydial infection Pregnancy rates ( method and user ) were evaluated for 2245 women who participated in the phase III clinical trials of the Today contraceptive sponge . User and method pregnancy rates were similar for women of different ages and parities . The 1-year method and user pregnancy rates ( life table per 100 women ) were 8.2 and 5.6 , respectively A re analysis of data from two clinical studies --in which 1,439 women were r and omly assigned to use either the contraceptive sponge or the diaphragm and 1,394 women were r and omly assigned to use either the cervical cap or the diaphragm -- found first-year probabilities of failure during typical use of 17 % for the sponge , 18 % for the cervical cap and 13 - 17 % for the diaphragm . The first-year probabilities of failure during perfect use are 11 - 12 % for the sponge , 10 - 13 % for the cervical cap and 4 - 8 % for the diaphragm . The probability of failure during perfect use is significantly higher among women who have given birth than among those who have not for users of the sponge ( 19 - 21 % vs. 9 - 10 % ) and users of the cervical cap ( 26 - 27 % vs. 8 - 10 % ) , but not for users of the diaphragm |
12,418 | 19,017,416 | In conclusion , using ultrasound to identify women at risk of cervical insufficiency because of a history of PTD reduces cerclage rates and results in similar pregnancy outcomes as cerclage placement on the basis of history alone . | UNLABELLED The aim of this systematic review was to compare pregnancy outcomes and cerclage-related complications of ultrasound-predicated versus history-predicated cerclage in patients at risk of cervical insufficiency due to a history of preterm delivery ( PTD ) . | BACKGROUND Infants born very preterm ( <33 weeks ) are at increased risk of neurocognitive deficits . Their neurodevelopmental outcome up to age 8 years can be predicted by neonatal ultrasonography , but little is known of their later function . We investigated the effect of very preterm birth on brain structure and neurocognitive and behavioural functioning in adolescence . METHODS A cohort of 105 infants born before 33 weeks of gestation in 1979 - 80 had ultrasonographic scans at University College Hospital , London , and were prospect ively examined at 1 , 4 , and 8 years . At age 14 - 15 years , 72 of those who remained in UK ( cases ) and 21 age-matched full-term controls underwent brain magnetic resonance imaging ( MRI ) , as well as neurological , cognitive , and behavioural assessment . MRI images were assessed by two neuroradiologists unaware of ultrasonographic findings or case or control status . FINDINGS Of the 72 cases , 40 had unequivocally abnormal MRI and 15 had equivocal scans . Of the 21 controls , one had abnormal and five equivocal MRI . Abnormalities of ventricles , corpus callosum , and white matter were especially common in cases . More brain lesions were identified by MRI than by neonatal ultrasonography . The cases had significantly more reading , adjustment , and neurological impairments than controls , but their behaviour was significantly related to MRI abnormality . INTERPRETATION Individuals born very preterm show an excess of neurocognitive and behavioural problems in adolescence , and more than half have abnormal MRI brain scans OBJECTIVE To assess whether cervical cerclage in women deemed to be at increased risk of cervical incompetence prolongs pregnancy and thereby improves fetal and neonatal outcome . DESIGN Multicentre r and omised controlled trial . SETTING Hospitals in the United Kingdom , France , Hungary , Norway , Italy , Belgium , Zimbabwe , South Africa , Icel and , Irel and , the Netherl and s and Canada . SUBJECTS One thous and two hundred and ninety-two pregnant women whose obstetricians were uncertain whether to recommend cervical cerclage , most of whom had a history of early delivery or cervical surgery . INTERVENTIONS Cervical cerclage was compared with a policy of withholding the operation unless it was considered to be clearly indicated . MAIN OUTCOME MEASURES Delivery before 33 completed weeks , preterm delivery ( < 37 weeks ) , and vital status of the baby after completion of the pregnancy . RESULTS The overall preterm delivery rate was 28 % . There were fewer deliveries before 33 weeks in the cerclage group ( 83 ( 13 % ) compared with 110 ( 17 % ) , P = 0.03 ) and this difference reflected deliveries characterised by features of cervical incompetence ( painless cervical dilatation and prelabour rupture of the membranes ) . There was a corresponding difference in very low birthweight deliveries ( 63 ( 10 % ) compared with 86 ( 13 % ) , P = 0.05 ) . The difference in the overall rate of miscarriage , stillbirth or neonatal death ( 55 ( 9 % ) compared with 68 ( 11 % ) ) was less marked and was not statistically significant . The use of cervical cerclage was associated with increased medical intervention and a doubling of the risk of puerperal pyrexia . CONCLUSIONS These results suggest that the operation had an important beneficial effect in 1 in 25 cases in the trial ( 95 % confidence interval ( CI ) 1 in 12 to 1 in 300 sutures ) . Its use is associated with increased medical intervention and puerperal pyrexia . Nevertheless , this trial suggests that , on balance , cervical cerclage should be offered to women at high risk , such as those with a history of three or more pregnancies ending before 37 weeks gestation Objective : The aim of the present study was to compare the outcome of pregnancies among patients with suspected cervical incompetence treated either by elective cervical cerclage or an alternative management program involving cervical surveillance To determine the value of transvaginal sonography in women with a previous history of second trimester miscarriage due to cervical incompetence , 55 patients were subjected to either elective cervical cerclage or follow-up ( every second patient ) with weekly evaluations of the cervix by transvaginal ultrasonography . Emergency cerclage was applied when significant cervical changes were noted . All patients were evaluated with cervical cultures and ultrasound . Women with infection , fibroids , uterine malformations and multiple pregnancies were excluded from the study . The study population was divided in two groups . In group I ( n=27 ) elective cerclage was applied during the 14th week . Women in group II ( n=28 ) were subjected to serial weekly evaluations of the cervix by transvaginal ultrasonograms . In 18 cases emergency cerclage was applied due to significant cervical changes . In group I , labor started before the 33rd week in two cases ( 7.4 % ) , between 33 and 37 weeks in nine ( 33.3 % ) and after the 37th week in 16 cases ( 59.2 % ) . Out of the 18 patients in group II who had cervical cerclage after ultrasonographic evaluation , four ( 22.2 % ) delivered before the 33rd week , three ( 16.6 % ) between 33 and 37 weeks and 11 ( 61.1 % ) after the 37th week . No statistical difference was noted between the two groups referring to pregnancy outcome ( p<0.1 ) . We concluded that ultrasound-guided management despite cervical shortening , does not result in unfavorable pregnancy outcome . A significant number of patients can avoid the operation OBJECTIVE The objective of this study was to compare different management strategies for women at risk for cervical incompetence . STUDY DESIGN In an ongoing r and omized trial patients with a previous preterm delivery at < 34 weeks ' gestation who met clinical criteria for the diagnosis of cervical incompetence are allocated to receive a prophylactic cerclage ( prophylactic cerclage group ) or not ( observational group ) in a proportion of 1:2 . Transvaginal ultrasonographic follow-up examination of the cervix is performed in both groups . When a patient of the latter group has a cervical length < 25 mm at < 27 weeks ' gestation , a further r and om assignment of therapeutic cerclage or no cerclage is performed . The analysis is by intent to treat . RESULTS Primary r and om assignment allocated 23 women to the prophylactic cerclage group and 44 to the observational group . Both groups were comparable with respect to obstetric history . No significant difference was found between the prophylactic cerclage group and the observational group in preterm delivery at < 34 weeks ' gestation ( 3/23 vs 6/44 , respectively ) and neonatal survival ( 21/23 vs 41/44 , respectively ) . A cervical length < 25 mm was found in 18 patients ( 41 % ) in the observational group at a mean gestational age of 19.1 + /- 2.9 weeks ' gestation . Incidence of preterm delivery at < 34 weeks ' gestation was significantly higher in the group with short cervical length ( 6/18 vs 0/26 ; P = .003 ) . Secondary r and om assignment of the 18 patients with short cervical length allocated 10 to undergo therapeutic cerclage . Preterm delivery at < 34 weeks ' gestation was significantly less frequent in the therapeutic cerclage group ( 1/10 vs 5/8 ) . CONCLUSION Transvaginal ultrasonographic serial follow-up examinations of the cervix in women at risk for cervical incompetence , with secondary intervention as indicated , appears to be a safe alternative to the traditional prophylactic cerclage . Transvaginal ultrasonographic follow-up examination of the cervix can save the majority of women from unnecessary intervention . Placement of a therapeutic cerclage may reduce the incidence of preterm delivery at < 34 weeks ' gestation among high-risk patients BACKGROUND The role of the cervix in the pathogenesis of premature delivery is controversial . In a prospect i ve , multicenter study of pregnant women , we used vaginal ultrasonography to measure the length of the cervix ; we also documented the incidence of spontaneous delivery before 35 weeks ' gestation . METHODS At 10 university-affiliated prenatal clinics , we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies . We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery . RESULTS We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks . Spontaneous preterm delivery ( at less than 35 weeks ) occurred in 126 of the women ( 4.3 percent ) examined at 24 weeks . The length of the cervix was normally distributed at 24 and 28 weeks ( mean [ + /- SD ] , 35.2 + /- 8.3 mm and 33.7 + /- 8.5 mm , respectively ) . The relative risk of preterm delivery increased as the length of the cervix decreased . When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile , the relative risks of preterm delivery among the women with shorter cervixes were as follows : 1.98 for cervical lengths at or below the 75th percentile ( 40 mm ) , 2.35 for lengths at or below the 50th percentile ( 35 mm ) , 3.79 for lengths at or below the 25th percentile ( 30 mm ) , 6.19 for lengths at or below the 10th percentile ( 26 mm ) , 9.49 for lengths at or below the 5th percentile ( 22 mm ) , and 13.99 for lengths at or below the 1st percentile ( 13 mm ) ( P < 0.001 for values at or below the 50th percentile ; P = 0.008 for values at or below the 75th percentile ) . For the lengths measured at 28 weeks , the corresponding relative risks were 2.80 , 3.52 , 5.39 , 9.57 , 13.88 , and 24.94 ( P < 0.001 for values at or below the 50th percentile ; P = 0.003 for values at the 75th percentile ) . CONCLUSIONS The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy OBJECTIVE To compare pregnancy outcome for women at risk of preterm delivery undergoing elective cervical cerclage in the first trimester or serial transvaginal assessment of cervical length with cerclage only if indicated ( control cases ) . DESIGN A matched case control study . SETTING Prematurity clinic at two London teaching hospitals . POPULATION Women at high risk for preterm delivery . METHODS Cases of elective cervical cerclage were matched for maternal age , ethnic group , previous cervical surgery , previous second trimester loss and early preterm delivery to women undergoing serial ultrasound surveillance of cervical length . Pregnancy outcome data was collected . Data was analysed using Fisher 's exact , Mann-Whitney and Student 's t-tests . MAIN OUTCOME MEASURES Gestation at delivery , rate of delivery < 24 , 24 - 32 and 32 - 37 weeks gestation . RESULTS Thirty-nine cases of elective cervical cerclage were matched to control cases . Both groups were similar for maternal age , ethnic group , previous cervical surgery , previous second trimester loss and early preterm delivery . Cervical cerclage was performed in 14 ( 36 % ) of the control cases due to cervical changes . There was no significant difference in median gestation at delivery ( 266 days versus 260 days P=0.9 ) , number delivering < 24 weeks ( 15 % versus 13 % P=0.9 ) , at 24 - 32 weeks ( 7.5 % versus 15 % P=0.6 ) and at 32 - 37 weeks ( 15 % versus 13 % P=0.9 ) . CONCLUSION Serial transvaginal ultrasound surveillance of cervical length in women at high risk of preterm delivery appears to reduce cerclage rates without compromising pregnancy outcome . A large multicentered r and omised trial is required to confirm these findings Summary . A total of 506 women at moderate risk of preterm delivery were r and omly allocated to either cervical cerclage or a control group . Significantly more women in the group allocated to cerclage were admitted to hospital for reasons other than the operation and more received oral toco‐lytic drugs . There were also more caesarean sections and more preterm deliveries in the women allocated to cerclage although the differences between the two groups were small and not statistically significant |
12,419 | 18,359,430 | CONCLUSION There are a growing number of evidence -based strategies for VAP prevention , which , if applied in practice , may reduce the incidence of this serious nosocomial infection | BACKGROUND Ventilator-associated pneumonia ( VAP ) is an important cause of morbidity and mortality in ventilated critically ill patients .
PURPOSE To develop evidence -based guidelines for the prevention of VAP . | Objective To determine the attributable cost of ventilator-associated pneumonia from a hospital-based cost perspective , after adjusting for potential confounders . Design Patients admitted between January 19 , 1998 , and December 31 , 1999 , were followed prospect ively for the occurrence of ventilator-associated pneumonia . Hospital costs were defined by using the hospital cost accounting data base . Setting The medical and surgical intensive care units at a suburban , tertiary care hospital . Patients Patients requiring > 24 hrs of mechanical ventilation . Interventions None . Measurements and Main Results We measured occurrence of ventilator-associated pneumonia , in-hospital mortality rate , total intensive care unit ( ICU ) and hospital lengths of stay ( LOS ) , and total hospital cost per patient . Ventilator-associated pneumonia occurred in 127 of 819 patients ( 15.5 % ) . Compared with uninfected , ventilated patients , patients with ventilator-associated pneumonia had a higher Acute Physiology and Chronic Health Evaluation II score on admission ( p < .001 ) and were more likely to require multiple intubations ( p < .001 ) , hemodialysis ( p < .001 ) , tracheostomy ( p < .001 ) , central venous catheters ( p < .001 ) , and corticosteroids ( p < .001 ) . Patients with ventilator-associated pneumonia were more likely to be bacteremic during their ICU stay ( 36 [ 28 % ] vs. 22 [3%];p < .001 ) . Patients with ventilator-associated pneumonia had significantly higher unadjusted ICU LOS ( 26 vs. 4 days;p < .001 ) , hospital LOS ( 38 vs. 13 days;p < .001 ) , mortality rate ( 64 [ 50 % ] vs. 237 [34%];p < .001 ) , and hospital costs ( $ 70,568 vs. $ 21,620 , p < .001 ) . Multiple linear regression , controlling for other factors that may affect costs , estimated the attributable cost of ventilator-associated pneumonia to be $ 11,897 ( 95 % confidence interval = $ 5,265–$26,214;p < .001 ) . Conclusions Patients with ventilator-associated pneumonia had significantly longer ICU and hospital LOS , with higher crude hospital cost and mortality rate compared with uninfected patients . After we adjusted for underlying severity of illness , the attributable cost of ventilator-associated pneumonia was approximately $ 11,897 Objective : To determine whether use of a single heat and moisture exchanger ( HME ) for ≤120 hrs affects efficiency , resistance , level of bacterial colonization , frequency rate of nosocomial pneumonia , and cost compared with changing the HME every 24 hrs . Design : Prospect i ve , controlled , r and omized , unblinded study . Setting : Surgical intensive care unit at a university teaching hospital . Patients : A total of 220 consecutive patients requiring mechanical ventilation for > 48 hrs . Interventions : Patients were r and omized to one of three groups : a ) hygroscopic HME ( Aqua+ ) changed every 24 hrs ( HHME‐24 ) ; b ) hydrophobic HME ( Duration HME ) changed every 120 hrs ( HME‐120 ) ; and c ) hygroscopic HME ( Aqua+ ) changed every 120 hrs ( HHME‐120 ) . Devices in all groups could be changed at the discretion of the staff when signs of occlusion or increased resistance were identified . Measurements and Main Results : Daily measurements of inspired gas temperature , inspired relative humidity , and device resistance were made . Additionally , daily cultures of the patient side of the device were accomplished . The frequency rate of nosocomial pneumonia was made by using clinical criteria . Ventilatory support variables , airway care , device costs , and clinical indicators of humidification efficiency ( sputum volume , sputum efficiency ) were also recorded . Prolonged use of both hygroscopic and hydrophobic devices did not diminish efficiency or increase resistance . There was no difference in the number of colony‐forming units from device cultures over the 5‐day period and no difference between colony‐forming units in devices changed every 24 hrs compared with devices changed after 120 hrs . The average duration of use was 23 ± 4 hrs in the HHME‐24 group , 73 ± 13 hrs in the HME‐120 group , and 74 ± 9 hrs in the HHME‐120 group . Mean absolute humidity was greater for the hygroscopic devices ( 30.4 ± 1.1 mg of H2O/L ) compared with the hydrophobic devices ( 27.8 ± 1.3 mg of H2O/L ) . The frequency rate of nosocomial pneumonia was 8 % ( 8:100 ) in the HHME‐24 group , 8.3 % ( 5:60 ) in the HME‐120 group , and 6.6 % ( 4:60 ) in the HHME‐120 group . Pneumonia rates per 1000 ventilatory support days were 20:1000 in the HHME‐24 group , 20.8:1000 in the HME‐120 group , and 16.6:1000 in the HHME‐120 group . Costs per day were $ 3.24 for the HHME‐24 group , $ 2.98 for the HME‐120 group , and $ 1.65 for the HHME‐120 group . Conclusions : Changing the hydrophobic or hygroscopic HME after 3 days does not diminish efficiency , increase resistance , or alter bacterial colonization . The frequency rate of nosocomial pneumonia was also unchanged . Use of HMEs for > 24 hrs , up to 72 hrs , is safe and cost effective Objective : To document the effect of gingival and dental plaque antiseptic decontamination on the rate of nosocomial bacteremias and respiratory infections acquired in the intensive care unit ( ICU ) . Design : Prospect i ve , multicenter , double-blind , placebo-controlled efficacy study . Setting : Six ICUs : three in university hospitals and three in general hospitals . Patients : A total of 228 nonedentulous patients requiring endotracheal intubation and mechanical ventilation , with an anticipated length of stay ≥5 days . Interventions : Antiseptic decontamination of gingival and dental plaque with a 0.2 % chlorhexidine gel or a placebo gel , three times a day , during the entire ICU stay . Measurements and Main Results : Demographic and clinical characteristics , organ function data ( Logistic Organ Dysfunction score ) , severity of condition ( Simplified Acute Physiologic Score ) , and dental plaque status were assessed at baseline and until 28 days . Bacteriologic sampling of dental plaque and saliva was done every 5 days , and blood , tracheal aspirate , and bronchoalveolar lavage cultures were performed when appropriate . The primary efficacy end point was the incidence of bacteremia , bronchitis , and ventilator-associated pneumonia , expressed as a percentage and per 1000 ICU days . All baseline characteristics were similar between the treated and the placebo groups . The incidence of nosocomial infections was 17.5 % ( 13.2 per 1000 ICU days ) in the placebo group and 18.4 % ( 13.3 per 1000 ICU days ) in the plaque antiseptic decontamination group ( not significant ) . No difference was observed in the incidence of ventilator-associated pneumonia per ventilator or intubation days , mortality , length of stay , and care loads ( secondary end points ) . On day 10 , the number of positive dental plaque cultures was significantly lower in the treated group ( 29 % vs. 66 % ; p < .05 ) . Highly resistant Pseudomonas , Acinetobacter , and Enterobacter species identified in late-onset ventilator-associated pneumonia and previously cultured from dental plaque were not eradicated by the antiseptic decontamination . No side effect was reported . Conclusions : Gingival and dental plaque antiseptic decontamination significantly decreased the oropharyngeal colonization by aerobic pathogens in ventilated patients . However , its efficacy was insufficient to reduce the incidence of respiratory infections due to multiresistant bacteria BACKGROUND The purpose of this study was to compare the performance of heat and moisture exchanger filters with heated humidifying systems in the mechanical ventilator circuit on the incidence of ventilator-associated pneumonia ( VAP ) and bacterial colonization . METHOD Two hundred and forty-three consecutive patients who required mechanical ventilation for 48 hours or more in the adult intensive care unit were r and omized to either a heat and moisture exchanger ( HME ) or a heated humidifying breathing circuit . RESULTS The VAP rate among the group with HME was 11.4 % ; the rate among the group with heated humidifying system ( HHS ) was 15.8 % . The difference was not statistically significant . Approximately 68 % of the patients in the HME group had no pathogen isolated compared with 50 % of the patients in the HHS group . This difference was statistically significant ( P = .006 ) . However , the distribution of the pathogens among those patients who had the isolated pathogens was mostly identical in the 2 groups . CONCLUSION Even though the study did not find HME to be significantly advantageous over the HHS , in as much as VAP rate is concerned , other advantages such as reduced nurses workload , reduced financial cost , and better safety made HME a more favorable device for use in our adult intensive care unit This a r and omized clinical trial in which 20 patients were prospect ively evaluated for the incidence of ventilator-associated pneumonia ( VAP ) , of whom 12 received endotracheal suctioning by an open-suction method and 8 by a closed-suction method . Differences in the incidence of VAP was not significantly different ( p = 0.4 ) between closed and open suctioning . Differences in Acute Physiology and Chronic Health Evaluation II , duration of entubation , and the use of steroids were all not significant . All patients in the study used H2 antagonist and a nasogastric tube . Proceeding with the study will involve a sample increase with a possible change in the results Nosocomial pneumonia is the leading cause of death among all hospital-acquired infections [ 1 ] . The estimated incidence of nosocomial pneumonia in intensive care units ranges from 10 % to 65 % ; most studies [ 2 - 6 ] show case fatality rates of more than 20 % . Ventilator-associated pneumonia specifically refers to nosocomial pneumonia that develops in a mechanically ventilated patient and that was not present at the time of airway intubation [ 7 ] . Various clinical risk factors have been associated with an increased incidence of ventilator-associated pneumonia , either because they predispose the patient to bacterial colonization of the oropharynx and stomach ( for example , the administration of antacids or histamine-2-receptor antagonists ) or because they facilitate aspiration of contaminated contents from these sites ( for example , supine positioning ) [ 1 , 2 , 8 , 9 ] . Craven and colleagues [ 10 ] first showed that the frequency of ventilator circuit changes also influences the incidence of ventilator-associated pneumonia . They found that changing circuits every 24 rather than every 48 hours was independently associated with the occurrence of nosocomial pneumonia [ 10 ] . This association has been attributed to increased manipulation of the patient , the endotracheal tube , and the ventilator circuit , which results in increased aspiration of contaminated tubing condensate or upper airway secretions [ 10 , 11 ] . More recently , several groups of investigators have found that ventilator circuits can be used safely for more than 48 hours without increasing the incidence of nosocomial pneumonia [ 12 - 16 ] . However , because of limitations in the design of these studies and the small number of patients prospect ively examined , the Centers for Disease Control and Prevention has given no clear recommendation for the maximum length of time that ventilator circuits can safely be left in place during prolonged mechanical ventilation [ 17 ] . This has result ed in the development of ambiguous guidelines about the frequency with which ventilator circuits should be changed [ 18 , 19 ] and in a call for well- design ed investigations to resolve this issue [ 20 ] . We did a r and omized , controlled trial to compare the effect and cost-efficacy of routine and no routine ventilator circuit changes in patients having prolonged mechanical ventilation . Our main goals were to determine 1 ) the incidence and outcome of ventilator-associated pneumonia in patients receiving scheduled ventilator circuit changes and 2 ) whether this incidence was increased in patients whose ventilator circuits remained unchanged . Methods Study Location and Patients The study was conducted at two university-affiliated teaching hospitals : Barnes Hospital ( 900 beds ) and Jewish Hospital ( 450 beds ) . During a 7-month period ( June 1994 to December 1994 ) , all patients receiving mechanical ventilation in the intensive care units of these hospitals ( surgical , trauma , medical , cardiothoracic , and neurosurgical units at Barnes Hospital ; surgical , medical , and cardiothoracic units at Jewish Hospital ) were potentially eligible for this investigation . Patients were entered into the trial if they were older than 18 years and had received mechanical ventilation for more than 5 days . Mechanical ventilation for more than 5 days was predetermined , on the basis of our previous experience at these institutions [ 2 , 21 ] , to be necessary so that a more homogeneous cohort of patients requiring prolonged mechanical ventilation could be accrued . Patients were excluded if they were likely to be extubated within 24 hours of r and omization , if they had transferred from other hospitals and had already received mechanical ventilation for more than 24 hours , if they had had lung transplantation , or if they had active hemoptysis . Barnes Hospital and Jewish Hospital share the same respiratory therapy and infection control departments . The study was approved by the Washington University School of Medicine Human Studies Committee and the Institutional Review Board of Jewish Hospital . Both waived the requirement for informed consent because this study was a quality assessment of two low-risk practice s already in clinical use . Study Design Patients were r and omly assigned to receive no routine ventilator circuit changes or circuit changes every 7 days within 24 hours of meeting eligibility criteria . A schedule of changing ventilator circuits every 7 days was selected on the basis of available clinical data [ 12 - 16 ] and our survey of 16 regional medical centers ( DM Baker . Unpublished communication ) . Stratification according to hospital site was done before r and omization to control for differences in patient population s and health care personnel . R and omization within each hospital was done using opaque , sealed envelopes , which were opened at the time each patient was enrolled in the study . For the purpose s of this investigation , ventilator circuits were defined to include gas delivery tubing , humidifier water reservoirs , water traps , and medication delivery devices ( such as metered-dose inhaler chambers or adapters ) . Ventilator circuits could be changed at any time , at the discretion of individual care providers ( physicians , nurses , and respiratory therapists ) , secondary to a mechanical failure of the ventilator circuit ( such as an air leak ) or visible soil ( such as that result ing from hemoptysis or aspirated emesis ) . Scheduled ventilator circuit changes were done during the evening or night shifts to minimize the identification of individual patient group assignments to blinded investigators . All nonscheduled circuit changes were done when an appropriate indication for the circuit change ( that is , a mechanical defect or soil ) was identified . Patients transferred to the operating room for a surgical procedure ( such as tracheotomy ) or to diagnostic radiology received the same mechanical ventilator and circuit when they returned to the intensive care unit . The ventilators used for this study included Siemens Servo 900C ( Siemens-Elema Ventilator Systems , Schaumburg , Illinois ) , Puritan-Bennett 700 Series ( Puritan-Bennett Corporation , Carlsbad , California ) , and Bird 8400 Series ventilators ( Bird Products Corporation , Palm Springs , California ) . All ventilators were equipped with wick-type humidifiers ( Concha Therm III Plus , Hudson Respiratory Care , Inc. , Temecula , California ) filled with sterile irrigation water . All ventilator circuits were disposable ( Hudson Respiratory Care , Inc. , model 1613 ) and equipped with Y connectors . Each ventilator circuit had an attached trap for the collection of tubing condensate ( Marquest Medical Products , Inc. , Englewood , Colorado ) . As per our st and ard procedure , all ventilator circuits were monitored at least every 2 hours and water traps were emptied when full . Data Collection For all study patients , the following characteristics were prospect ively recorded by one of the investigators : age , sex , diagnosis at hospital admission , indication for mechanical ventilation , Premorbid Lifestyle score , the ratio of arterial blood oxygen tension to the concentration of inspired oxygen ( Pao 2 : Fio 2 ) , severity of illness based on APACHE II ( Acute Physiology and Chronic Health Evaluation [ 22 ] ) scores , the Organ System Failure Index , and the occurrence of a witnessed aspiration event . Specific processes of medical care examined to assess risk factors for ventilator-associated pneumonia were the administration of antacids or histamine-2-receptor antagonists , pharmacologic aerosol treatments during mechanical ventilation ( such as bronchodilators , antibiotics , and mucolytics ) , fiberoptic bronchoscopy , surgical tracheostomy , and the number of ventilator circuit changes done and the indications for those changes ( scheduled according to the study protocol , soil , or mechanical defect ) . Two of the investigators made daily rounds in the intensive care units of each hospital to identify eligible patients . Patients entered into the study were prospect ively followed for the occurrence of ventilator-associated pneumonia until they were successfully weaned from mechanical ventilation , were discharged from the hospital , or died . All patients suspected by these investigators of having ventilator-associated pneumonia were prospect ively and independently review ed by another investigator who was blinded to the patient 's treatment group assignment . The diagnosis of ventilator-associated pneumonia was strictly based on the predetermined criteria described below . Patients could not be entered into the study more than once during the same hospitalization , and only the first episode of ventilator-associated pneumonia was evaluated . In addition to the occurrence of ventilator-associated pneumonia , secondary outcomes assessed included the length of hospitalization , the duration of mechanical ventilation , hospital mortality , and mortality directly attributed to ventilator-associated pneumonia . All study variables were recorded in data collection books maintained at each of the participating hospitals . Definitions All definitions were selected prospect ively as part of the original study design . The Premorbid Lifestyle score was used as previously defined [ 23 ] : Zero indicated that the patient was employed without restriction ; 1 indicated that the patient was independent , fully ambulatory , not employed , or employed with restriction ; 2 indicated that the patient had restricted activities , could live alone and get out of the house to do basic necessities , or had severely limited exercise ability ; 3 indicated that the patient was housebound , could not get out of the house unassisted , could not live alone , or could not do heavy chores ; and 4 indicated that the patient was bed- or chairbound . We calculated APACHE II scores on the basis of clinical data available from the 24-hour period before study enrollment ( day 5 of mechanical ventilation ) . The Organ System Failure Index was modified from that used by Rubin and coworkers [ 24 ] . One point was given for STUDY OBJECTIVES We hypothesized that continuous , automatic turning utilizing a patient-friendly , low air loss surface would reduce the incidence of early ICU pneumonia in selected groups of critically ill medical patients . DESIGN Prospect i ve , r and omized , controlled clinical trial . SETTING Medical ICU of a large community teaching hospital . PATIENTS One hundred twenty-four critically ill new admissions to the medical ICU at Charity Hospital in New Orleans . INTERVENTIONS Patients were prospect ively r and omized within one of five diagnosis-related groups (DRG)--sepsis ( SEPSIS ) , obstructive airways disease ( OAD ) , metabolic coma , drug overdose , and stroke -- to either routine turning on a st and ard ICU bed or to continuous turning on an oscillating air-flotation bed for a total of five days . MEASUREMENTS AND RESULTS Patients were monitored daily during the treatment period for the development of pneumonia . The incidence of pneumonia during the first five ICU days was 22 percent in patients r and omized to the st and ard ICU bed vs 9 percent for the oscillating bed ( p = 0.05 ) . This treatment effect was greatest in the SEPSIS DRG ( 23 percent vs 3 percent , p = 0.04 ) . Continuous automatic oscillation did not significantly change the number of days of required mechanical ventilation , ICU stay , hospital stay , or hospital mortality overall or within any of the DRGs . CONCLUSIONS We conclude that air-supported automated turning during the first five ICU days reduces the incidence of early ICU pneumonia in selected DRGs ; however , this form of automated turning does not reduce other measured clinical outcome parameters Nosocomial pneumonia develops in 0.5 to 1 patient per 100 hospital admissions and is associated with high morbidity and mortality [ 1 , 2 ] . Mechanically ventilated patients have a high risk for developing nosocomial pneumonia ; indeed , ventilator-associated pneumonia has a cumulative incidence ranging from 18 % to 60 % , and it was found in more than 70 % of patients who died of acute lung injury [ 3 - 6 ] . Nosocomial pneumonia is frequently caused by gram-negative bacilli and usually results from aspiration of bacteria from the colonized oropharynx [ 7 - 9 ] . Colonization of the pharynx by gram-negative bacilli [ 9 - 12 ] is associated with chronic illness and previous use of antibiotic agents and endotracheal intubation ; in the pathogenesis of ventilator-associated pneumonia , the relation between chronic aspiration of colonized secretions through a tracheal cuff and the development of pneumonia is well established [ 13 , 14 ] . Several strategies , such as infection-control measures ( for example , h and -washing ) [ 15 , 16 ] , preservation of a normal gastric pH , or topical administration of a nonabsorbable antibiotic combination ( selective digestive decontamination ) have been recommended to decrease the incidence of ventilator-associated pneumonia [ 17 - 19 ] . However , further investigation is required to define the role of selective digestive decontamination in selected patients in intensive care units ; in addition , there is considerable concern about the risk for selection of resistant strains . Recently , two studies suggested the possibility of preventing the chronic aspiration of subglottic secretions either by changes in body position [ 20 ] or by manual intermittent aspiration of subglottic secretions [ 21 ] , two alternative approaches for preventing ventilator-associated pneumonia . We evaluated the usefulness of continuous aspiration of subglottic secretions in the prevention of ventilator-associated pneumonia in a medicalsurgical intensive care unit . Methods Patients All patients admitted to the intensive care unit of the Sabadell Hospital from June 1990 to March 1993 who required intubation and were expected to receive mechanical ventilation for at least 72 hours were eligible for study . The intubation could be done either in the intensive care unit or in the emergency department . Patients were excluded if they were intubated in other areas of the hospital , if they carried a tracheostomy tube , or if they developed a pneumonia or died during the first 72 hours of mechanical ventilation . Study was considered complete when a patient was extubated , when a tracheostomy was done , when a patient died , or when ventilator-associated pneumonia was diagnosed . The follow-up period consisted of the patient 's remaining stay in the intensive care unit . All patients were intubated with the same type of endotracheal tube ( Hi-Lo Evac ; Mallinckrodt Laboratories , Athlone , Irel and ) , which incorporates a dorsal separate lumen ending into the subglottic area by creating a large elliptical dorsal opening above the cuff for aspiration of subglottic secretions ( Figure 1 ) . The size of each endotracheal tube was selected by the attending physician ; after intubation , the correct position of endotracheal tube was verified by a roentgenogram of the chest . Figure 1 . Diagram of continuous aspiration of subglottic secretions . Patients were r and omly assigned to receive continuous aspiration through the additional lumen from the endotracheal tube ( case- patients ) or to receive st and ard treatment in which the additional lumen remained closed ( control patients ) . Intra-cuff pressure was monitored every 4 hours ( Mallinckrodt GmbH , Mallinckrodt Laboratories , Neunkirchen-Seelscheid , Germany ) and was kept above 20 mm Hg . Subglottic drainage was continuous , and secretions were collected in a mucous collector ( Mocstrap ; Proclinics , Barcelona , Spain ) . The amount of secretions obtained daily was also recorded . If subglottic drainage was negative , the permeability was checked every 4 hours by injecting sterile saline serum into the evacuation lumen . All patients received stress ulcer prophylaxis with sucralfate . We did not use a selective decontamination regimen or antibiotic prophylaxis . The study protocol was review ed and approved by the hospital 's institutional review board for human studies . Data Collection and Definitions We prospect ively recorded each patient 's demographic characteristics , diagnosis at admission , and underlying diseases . The Acute Physiology and Chronic Health Evaluation ( APACHE ) II scoring system of Knaus and colleagues [ 22 ] was used to assess the severity of an acute illness . Several risk factors for ventilator-associated pneumonia were recorded , such as continuous sedation , previous surgery , multiple trauma , structural or pharmacologic coma ( score of 8 according to the Glasgow coma scale [ 23 ] ) , and use of muscle relaxants and antibiotic treatment during the intensive care unit stay . Ventilator-associated pneumonia was suspected in patients who met the following criteria after 72 hours of mechanical ventilation : fever ( body temperature 38.3 C ) , leukocytosis ( > 12 000 leukocytes/mm3 ) or leukopenia ( < 4000 leukocytes/mm3 ) , purulent secretions , and the presence of new and persistent pulmonary infiltrates . The diagnosis of pneumonia was confirmed by a positive protected specimen brush culture containing 103 colony-forming units (CFU)/mL or more , a positive bronchoalveolar lavage culture with 104 CFU/mL or more , or by a good clinical response to antibiotic agents . Additional criteria were the absence of a diagnosis other than pneumonia and pathologic findings consistent with pneumonia in patients who died and in whom autopsy was authorized . Ventilator-associated pneumonia was histologically diagnosed when foci of consolidation with intense polymorphonuclear leukocyte accumulation in the bronchioles and alveolar spaces were observed . Roentgenograms of the chest were interpreted by a radiologist who had no knowledge of patients ' treatment groups . Crude mortality rates included all deaths that occurred in the intensive care unit in patients with ventilator-associated pneumonia . Death was considered attributable to the pulmonary infection if the patient died before having any objective response to antimicrobial therapy or if the pulmonary infection was considered a contributing factor to death in patients with additional conditions . We used the definitions described by Knaus and colleagues [ 22 ] to define the underlying diseases . We considered previous surgery when a surgical procedure had been done within the present admission to the hospital and considered previous antibiotic treatment when a patient was receiving antibiotic agents at r and omization . Bacteriologic Examination In patients in whom ventilator-associated pneumonia was suspected , bronchoscopy was done while they were being ventilated with an Fio 2 of 1.0 and without positive end-expiratory pressure . All patients received midazolam as a sedative and atracurium as a relaxant while the bronchoscopy was done . The fiberoptic bronchoscope ( Olympus BF 20 ; Olympus Corp. , Tokyo , Japan ) was passed into the trachea through the endotracheal tube by a special connector ( Unimed Ltd. , Shaftesbury , United Kingdom ) and was advanced under visual control to the bronchial orifice of the abnormal lobe . The telescoping plugged catheter ( TAG Medical , Bobigny Cedex , France ) was inserted through the inner suction channel and was advanced to a wedged peripheral position . Airway secretions were obtained using a previously described technique [ 24 ] . For a bronchoalveolar lavage , the bronchoscope was sustained in a wedged position , and lavage was done with three 50-mL aliquots of sterile isotonic saline . The bronchoscope was then removed , and ventilation with an Fio 2 of 1.0 was continued for 15 minutes . After the protected specimen brush was transected into a sterile vial containing 1 mL of sterile lactate Ringer 's solution , the vial was vigorously agitated for at least 60 seconds to suspend all the material from the brush . Specimens were immediately sent to the laboratory for quantitative cultures . Aliquots of 0.01 mL were then taken from the original suspension and inoculated into blood agar , chocolate agar , anaerobic kanamicin blood agar , anaerobic blood agar , MacConkey agar , buffered charcoal yeast extract agar , and Sabouraud media . One 0.001-mL aliquot was also inoculated into chocolate agar media . Culture plates were incubated at 37 C under adequate aerobic and anaerobic conditions ; all plates except for the Sabouraud plates were evaluated for growth at 24 and 48 hours . For the protected specimen brush , bacterial counts of 103 CFU/mL or greater were used as the cutoff point to diagnose pneumonia . Two serial 10-fold dilutions were then done on the recovered bronchoalveolar lavage fluid , and 0.01-mL aliquots of the original suspension and each dilution were placed onto plates in the same way as for the protected specimen brush sample . All protected specimen brush and bronchoalveolar lavage fluid isolates were identified by st and ard laboratory techniques [ 25 ] . Two blood cultures were done simultaneously in all patients , as were pleural fluid cultures if present . Surveillance cultures for aerobic microorganisms in the subglottic secretions were obtained from patients in the continuous aspiration group and were repeated every 5 days until ventilator-associated pneumonia developed or until patients were extubated or died . Statistical Analysis We compared the characteristics of the two groups using the Student t-test or Mann-Whitney test for continuous variables and the chi-square test or Fisher exact test for categorical variables . We defined the cumulative incidence as the number of events divided by the number of patients and estimated risk ratios and 95 % CIs [ 26 ] . The incidence rate was defined as the number of events divided by the number of days the patient was at risk because of the presence of an endotracheal tube . We compared Patients hope that their doctors will correctly identify health problems , clearly articulate sensible options for managing each problem , wisely interpret the best available evidence about probable outcomes associated with each option , sensitively solicit patient preferences for each outcome , and thereby implement practice s that are likely to achieve the results patients care about . Groups of patients hope that doctors will work to prevent , detect , and treat health problems in a way that maximizes the public good achieved with available health care re sources . To meet these dual expectations , doctors face forbidding tasks of clinical decision making . Improved methods for preparing , appraising , and abstract ing overviews of available evidence about a clinical topic can bring a broader range of high- quality information within the busy practitioner 's grasp [ 1 - 4 ] . However , even well- design ed overviews often do not synthesize information about benefits , harms , and costs of medical practice s in a way that facilitates clinical decision making . Clinical practice guidelines have been defined as systematic ally developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances [ 5 ] . Guidelines that are based on sound scientific evidence , and a trustworthy process for judging the value of alternative practice s , could help physicians deal with the information overload they face . Existing practice guidelines , however , vary widely in their quality , and clinicians should carefully consider the validity and applicability of each guideline they read . We propose a structured format for abstract s of articles describing practice guidelines that is based on emerging principles of guideline development and evaluation [ 6 - 13 ] . The proposal is design ed to help readers obtain the key information needed to assess the applicability , importance , and validity of any guideline . The proposed structure for more informative abstract s of articles describing clinical practice guidelines has been review ed and pilot-tested by guideline developers , evaluators , and implementors and by groups of practicing clinicians . Early versions of the proposal were sent to consultants at the National Library of Medicine , the Institute of Medicine , the American College of Physicians ( ACP ) , and the Agency for Health Care Policy and Research . Subsequent versions of the proposal were pilot tested on various published guidelines and were assessed by selected health care organizations for applicability to guidelines under development . An improved proposal was sent to 82 persons active in guideline development , evaluation , and implementation . The Internal Medicine Center to Advance Research and Education circulated the proposal to volunteer practitioners , and the authors solicited feedback from physician and health administrator participants at three national workshops about practice guidelines . The proposal that follows represents an integration of the collective wisdom of our external review ers . ( A glossary of terms used in articles on clinical practice guidelines is supplied in the Appendix . ) Proposed Structure and Content for Abstract s of Articles Describing Clinical Practice Guidelines The proposed structure for abstract s of papers describing clinical practice guidelines is summarized in Table 1 . Key elements of the guideline development process are captured with statements about the principal objective and target of the guideline , the main practice options and outcomes that were considered , the nature of the evidence and values that were analyzed , the main benefits and harms expected from guideline implementation , the key recommendations , and a statement of whether the recommendations have been tested and by whom they have been endorsed . If details about guideline development methods or supporting evidence are published separately , then the abstract should indicate the existence of supporting documents and the most relevant parts of those should be summarized in the abstract . To be included in their entirety in the online bibliographic data bases of the National Library of Medicine , structured abstract s of clinical practice guidelines should not exceed 4096 characters ( approximately 500 words ) in length . Individual journals may have different requirements . Table 1 . Proposed Format for Structured Abstract s of Clinical Practice Guidelines Objective The abstract should state the objective of the guideline by identifying the targeted health problem , the targeted patients and physicians , and the main reason or reasons for developing new recommendations concerning this problem for this population . For guidelines primarily concerned with the management of health conditions , the stage of illness and intent to prevent , diagnose , treat , or palliate the disorder should be specified . For guidelines primarily concerned with health procedures , an intervention and its role in patient management should be defined . Targeted providers , setting s , and patients should be specified so that readers can tell who should do what , where it should be done , and to whom . A statement of objective also may specify why a new guideline is needed and how it should be used . Practice guidelines may be written to clarify or resolve clinical controversies , to communicate important new findings from clinical studies , or to promote more effective , efficient , or consistent physician practice s at less cost or risk to patients . Guidelines may be used concurrently to help physicians and patients make choices ( for example , clinical algorithms ) , retrospectively to compare physician choices to pre-established criteria ( for example , utilization review ) , or prospect ively to set limits on physician choices ( for example , preprocedure approval ) . Options Clinical practice guidelines pertain to clinical decisions . The nature of those decisions should be made explicit by disclosing the main management options considered . The abstract should list principal alternative preventive , diagnostic , or therapeutic strategies available to targeted clinicians and patients . Outcomes The abstract also should specify which health outcomes , such as death , morbidity , quality of life , economic costs , or changes in the process of health care were considered . Evidence To estimate the probable effect of a health intervention on an outcome , relevant data must be defined , gathered , and appraised . Readers need to know what kind of evidence was considered and what methods were used to select and combine evidence from different sources . Potential sources of evidence about clinical outcomes include the results of clinical studies ( published or unpublished ) , expert opinion , information contained in public or private health data bases , and direct input from patients or providers . Potential sources of evidence about economic outcomes include the results of cost-effectiveness studies , various fee schedules , and information contained in public or private health cl aims data bases . Potential methods of gathering evidence include computerized search es for articles that satisfy predetermined criteria , review s of bibliographies of relevant articles , and surveys of relevant persons or organizations [ 1 ] . The abstract should state whether explicit methods were used to combine results from scientific studies ( for example , meta- analysis ) or opinions of experts ( for example , Delphi technique ) [ 14 , 15 ] . The abstract may also indicate whether specific criteria were used to gauge the quality of information from different sources [ 16 , 17 ] . Scientific evidence regarding the likelihood of certain outcomes is often missing or conflicting . It is desirable for the strength of evidence supporting a guideline to be gauged in some way [ 16 ] . If gaps in the evidence were bridged formally ( for example , through use of decision- analysis models ) or informally ( for example , best guess of clinical experts ) , then major assumptions or areas of uncertainty should be acknowledged [ 11 ] . Because of the extraordinary time required to properly assemble and review evidence and then to achieve consensus about practice recommendations , the abstract of a practice guideline should specify the publication date s of the most recent evidence considered . If a sensitivity analysis was performed , then any major vulnerability of the guideline to weaknesses in the evidence should be acknowledged . These considerations may be summarized by qualifying a guideline as provisional by specifying date s for expiration or review , by listing studies in progress that could affect the guideline , or by identifying key research priorities . Values The declaration of a recommended practice presumes an implicit or explicit process for judging the relative desirability of the health , economic , and process outcomes associated with alternative practice s. These are matters of opinion and value . For example , in developing guidelines for breast cancer screening , it is necessary to weigh the value of preventing a death from breast cancer against the value of avoiding unnecessary harm or anxiety in women who do not have breast cancer . A high value placed on maximizing detection of asymptomatic malignancy may motivate an organization to recommend teaching self-examination of breasts to young women [ 18 ] . A relatively greater value placed on avoiding false-positive results may motivate others to not promote such programs [ 19 ] . Consequently , the principal sources of such values and the method by which judgments were made should be reported in guideline abstract s. At a minimum , the abstract should identify the major groups that participated in the process of assigning values to outcomes ( for example , generalist or specialist physicians , other health care providers , insurers , representatives of health organizations , and special-interest groups ) and whether patient preferences were represented . The abstract may also indicate the method used to synthesize opinions from Objective : The use of topical polymyxin and tobramycin to prevent intensive care infections is controversial . Moreover , these antibiotics are ineffective against methicillin-resistant Staphylococcus aureus . A decontamination regimen using mupirocin and chlorhexidine could prevent acquired infections , including those involving S. aureus . Because these two regimens could have a complementary role , we evaluated their effects when given both alone and combined . Design : The authors conducted a multiple-center , placebo-controlled , r and omized , double-blind study performed according to a 2 × 2 factorial design . Setting : The study was conducted at three polyvalent medical intensive care units at university-affiliated hospitals in France . Patients : Adult patients ( age , ≥18 yrs ) intubated for < 48 hrs who were likely to be ventilated for > 48 hrs . Intervention : Two regimens were used : topical administration of polymyxin/tobramycin ( or placebo ) and nasal mupirocin with chlorhexidine body washing ( or nasal placebo with liquid soap ) . The patients ( n = 515 ) received polymyxin/tobramycin alone ( n = 130 ) , mupirocin/chlorhexidine alone ( n = 130 ) , both regimens ( n = 129 ) , or all placebos ( n = 126 ) for the period of mechanical ventilation plus 24 hrs . Measurements and Main Results : The incidence of total infections acquired from the date of r and omization until the termination date of study treatments plus 48 hrs was assessed . There were fewer acquired infections with both regimens than with polymyxin/tobramycin alone ( odds ratio , 0.44 ; 95 % confidence interval , 0.26–0.75 ; p = .003 ) , mupirocin/chlorhexidine alone ( 0.43 ; 0.25–0.73 ; p = .002 ) , or all placebos ( 0.42 ; 0.25–0.72 ; p = .001 ) . There were no differences between polymyxin/tobramycin alone ( 0.95 ; 0.59–1.54 ; p = .84 ) and mupirocin/chlorhexidine alone ( 0.98 ; 0.60–1.58 ; p = .92 ) vs. all placebos . The probability of freedom from infection was higher with both regimens than with polymyxin/tobramycin alone ( p = .002 ) , mupirocin/chlorhexidine alone ( p < .001 ) , or all placebos ( p < .001 ) . Infection rates were also significantly lower with both regimens than with polymyxin/tobramycin alone ( p = .017 ) , mupirocin/chlorhexidine alone ( p < .001 ) , or all placebos ( p < .001 ) . Conclusion : Acquired infections were substantially reduced by mupirocin/chlorhexidine plus polymyxin/tobramycin , whereas each regimen given alone was ineffective . Whether both regimens could increase C and ida infections deserves further investigation OBJECTIVE To compare the degree of bacterial circuit colonization , frequency of ventilator-associated pneumonia ( VAP ) , character of respiratory secretions , rewarming of hypothermic patients , disposable costs , and air flow resistance in intensive care patients ventilated using either a heat and moisture exchanger ( HME ) or hot water ( HW ) humidifier circuit . DESIGN A prospect i ve , r and omized blinded trial of patients in the intensive care unit undergoing mechanical ventilation . SETTING A metropolitan teaching hospital . PATIENTS One hundred sixteen patients undergoing mechanical ventilation for a minimum period of 48 hrs were enrolled . INTERVENTIONS Patients were r and omized to three ventilation groups using a ) an HW circuit with a 2-day circuit change ( n = 41 ) ; or b ) a bacterial-viral filtering HME in the circuit , with either a 2-day ( n = 42 ) ; or c ) a 4-day circuit change ( n = 33 ) . MEASUREMENTS AND MAIN RESULTS Circuit colonization was assessed using quantitative culture of washings taken from the circuit tubing and semiquantitative culture of swabs from the Y connectors . Sixty-seven percent of HW circuits became contaminated compared with 12 % in the two HME groups ( p < .0001 ) . Median colony counts were lower in the HME groups ( p < .0001 ) . If circuits at first circuit change were contaminated in the HW group , 89 % of subsequent circuit changes became contaminated compared with 0 % and 25 % for the 2- and 4-day HME groups , respectively . The frequency of VAP , the time to resolution of admission hypothermia , and the volume and fluidity of secretions were similar for all groups . The resistance of the HME after 24 hrs of use was < 0.025 cm H2O/L at gas flows of 40 L/min . HME use result ed in a cost reduction of $ 1.48 (Australian)/day . CONCLUSIONS Circuits with a bacterial-viral filtering HME are less readily colonized by bacteria . Contamination is a r and om event . Humidification technique has no influence on the frequency rate of VAP , the effectiveness of rewarming , nor the character of the respiratory secretions . Breathing resistance is generally low and disposable costs are reduced when an HME is used The objective of this r and omized study was to compare the occurrence of nosocomial pneumonia in nasotracheally intubated patients who were r and omly allocated either to a systematic search of sinusitis by CT scan ( study group ) or not ( control group ) . A total of 399 patients were included : 272 male and 127 female ; mean age , 61 + /- 17 yr ; SAPS : 12.6 + /- 4.9 . The study group consisted of 199 patients and the control group consisted of 200 . In the study group , sinus CT scans were performed in case of fever at Days 4 and 8 and then every 7 d. Nosocomial sinusitis was defined as follows : fever of > /= 38 degrees C , radiographic ( sinusal air-fluid level or opacification on CT scan ) signs , and presence of purulent aspirate from the involved sinus puncture with > /= 10(3 ) cfu/ml . Patients with sinusitis received sinus lavage and intravenously administered antibiotics . In the study group , 80 patients experienced nosocomial sinusitis . In the control group , no patient was treated for a sinusitis . Ventilator-associated bronchopneumonia ( VAP ) was observed in 88 patients : 37 in the study group ( 1 mo Kaplan-Meier estimate , 34 % ) versus 51 in the control group ( 1 mo Kaplan-Meier estimate , 47 % ) ; ( p = 0.02 , log-rank test ; relative risk [ RR ] = 0.61 ; 95 % confidence interval [ CI ] , 0.40 to 0.93 ) . Two months overall mortality was estimated at 36 % in the study group versus 46 % in the control group ( p = 0.03 , log-rank test ; RR = 0.71 ; 95 % CI , 0.52 to 0.97 ) . We conclude that the occurrence of VAP in patients undergoing prolonged mechanical ventilation via a nasotracheal intubation can be prevented by the systematic search and treatment of nosocomial sinusitis . The effect on mortality should be confirmed Abstract Objectives : To document in intensive care unit ( ICU ) patients the effect of dental plaque antiseptic decontamination on the occurrence of plaque colonization by aerobic nosocomial pathogens and nosocomial infections . Design : Single-blind r and omized comparative study . Setting : A 16-bed adult intensive care unit in a university hospital . Patients : Patients consecutively admitted in the ICU with a medical condition suggesting an ICU stay of 5 days and requiring mechanical ventilation . Interventions : After r and omization , the treated group received dental plaque decontamination with 0.2 % chlorhexidine gel , three times a day during the ICU stay . The control group received st and ard oral care . Specific measurements : Dental status was assessed by the Caries-Absent-Occluded index ; the amount of dental plaque was assessed by a semi-quantitative plaque index . Bacterial sampling of dental plaque , nasal and tracheal aspirate , blood , and urine cultures were done on days 0 , 5 , 10 , and every week . Main results : Sixty patients were included ; 30 in the treated group and 30 in the control one ( mean age : 51±16 years ; mean Simplified Acute Physiological Score II : 35±14 points ) . On admission , no significant differences were found between both groups for all clinical and dental data . Compared with the control group , the nosocomial infection rate and the incidence densities related to risk exposition were significantly lower in the treated group ( 18 vs 33‰ days in the ICU and 10.7 vs 32.3‰ days of mechanical ventilation ; P<0.05 ) . These results were consistent with a significant preventive effect of the antiseptic decontamination ( Odds Ratio : 0.27 ; 95 % CI : 0.09 ; 0.80 ) with a 53 % relative risk reduction . There was a trend to a reduction of mortality , length of stay , and duration of mechanical ventilation . Conclusions : An antiseptic decontamination of dental plaque with a 0.2 % chlorhexidine gel decreases dental bacterial colonization , and may reduce the incidence of nosocomial infections in ICU patients su bmi tted to mechanical ventilation A total of 68 postoperative patients whose lungs were ventilated for more than 4 days were studied prospect ively during a one‐year study period to investigate the effect of the mode of intubation on the paranasal sinuses . After an initial X ray of the skull showing no pathological findings , patients were assigned r and omly to one of the study groups ; the lungs of patients in group A were ventilated via an orotracheal tube ( n = 32 ) , and patients in group B via a nasotracheal tube ( n = 36 ) . X ray examinations of the sinuses were performed at regular intervals . Diagnosis of sinusitis was confirmed by transantral needle puncture and culture of fluids obtained . Antibiotic regimens were altered according to laboratory testing . Two patients in group A developed signs of sinusitis in comparison to 15 patients in group B ( p < 0.01 ) . However , there were significantly more airway complications in the orotracheal group , particularly during the period of weaning from ventilation . We conclude that orotracheal intubation should be preferred as the routine route of intubation OBJECTIVE To assess the influence of the subglottic secretion drainage on the morbidity of ventilator associated pneumonia in mechanically ventilated patients . METHODS All cases requiring intubation in SICU were intubated with a special type endotracheal tube which has a small-bore cannula in its wall for subglottic secretion drainage . They were r and omly divided into two groups received subglottic secretion drainage(SSD ) and usual care(NON-SSD ) respectively . Bacterial culture of sample s from the oropharynx , subglottic secretions and lower respiratory tract were obtained periodically . The amount of subglottic secretion aspirated daily , ventilated days and the number of cases with VAP were recorded . Etiologic diagnosis of VAP was based on the quantitative bacterial culture of secretions obtained by protected specimen brush(PSB ) . RESULTS The morbidity of VAP in the SSD group ( n = 35 ) ( 23 % ) was lower than that in the NON-SSD group ( n = 33 ) ( 45 % ) ( P < 0.05 ) . The difference was due to the significant reduction of VAP caused by gram-positive cocci and Haemophilus influenzae organisms . However , no difference was observed in the incidence of VAP caused by non-fermental bacteria . After intubation the onset of VAP was delayed in SSD group ( 14 + /- 8 day ) as compared with the NON-SSD group ( 6 + /- 4 day ) ( P < 0.05 ) . The same organisms were isolated by PSB among 61 % ( 14/23 ) patients with VAP as what were previously isolated from the subglottic secretions . CONCLUSIONS The presence of subglottic secretion may be an origin of the pathogenetic organisms of VAP . The morbidity of VAP in mechanically ventilated patients can be reduced by SSD , especially for VAP caused by gram-positive cocci and Haemophilus influenzae organisms . SSD may be a simple and effective method for prevention of VAP Objective : To compare the ventilator-associated pneumonia ( VAP ) incidence rates in mechanically ventilated patients according to the type of endotracheal suctioning ( closed versus open ) . Setting : The Neurosurgery Intensive Care Unit of the Grenoble University Hospital , France . Design : A prospect i ve r and omised study performed after a 6-month period of nursing personnel training . Patients : One hundred four consecutive patients needing mechanical ventilation for more than 48 h were r and omised into two groups . To be eligible , patients had to have no active infection or respiratory affection in their passes . In the Stericath group ( S + , n = 54 ) , patients were not disconnected from the ventilator during suctioning . The others were routinely managed ( S– , n = 50 ) . In both groups patterns of frequency and duration of suctioning were performed according to a st and ardised protocol .¶ Measurements : The non-adjusted incidence rate of VAP was lower for S + than for S– ( 7.32 versus15.89 per 1000 patient-days , p = 0.07 ) . Multivariate analysis performed using the Cox model showed an adjusted risk of VAP 3.5 times higher in S– ( 95 % Cl : 11.00–12.33 ) . The risk being 4.3 higher in patients receiving gastric acid secretion inhibitors ( 1.08–16.82 ) . In non-censored cases ( n = 76 ) length of ICU stay increased by an average of 16.8 days when VAP was present ( p = 0.0008 ) . No adverse effect due to Stericath use was noted and volume of tracheal aspirate was similar between groups ( p = 0.178 ) . Conclusion : The use of Stericath reduced the incidence rate of VAP without demonstrating any adverse effect The kinetic treatment table ( KTT ) has been developed to prevent and treat complications of immobility . Because atelectasis and pneumonia may be related to immobility , we studied the effect of the KTT on the prevention and treatment of pulmonary complications in a prospect i ve r and omized study of 30 patients with severe traumatic injuries . All were receiving mechanical ventilation and were r and omly assigned to treatment with a KTT or a conventional bed . Both groups received conventional medical-surgical therapy while pulmonary function , chest roentgenograms , and the presence or absence of lung infection were monitored for one week . In the patients who began the study with a clear chest roentgenogram , atelectasis and pneumonia were significantly less frequent in those treated with a KTT ( P less than .05 ) . Thus , the KTT can reduce pulmonary complications in selected patients with multiple trauma . The effect of this benefit on overall outcome is uncertain This study was undertaken to assess whether oropharyngeal vancomycin may control oropharyngeal carriage and lower airway infection due to methicillin‐resistant Staphylococcus aureus ( MRSA ) acquired in the intensive care unit ( ICU ) . Secondary endpoints were the emergence of vancomycin-resistant enterococci , vancomycin-intermediate S. aureus and vancomycin consumption . A total of 84 patients , admitted to a medical/surgical ICU and mechanically ventilated for > 72 h , were r and omly assigned to control ( n=42 ) or test ( n=42 ) group . Both groups received the protocol of selective decontamination of the digestive tract , including polymyxin E , tobramycin and amphotericin B. Patients in the test group received 0.5 g of a 4 % vancomycin gel at 6‐h intervals in the oropharynx . Lower airway infections due to MRSA acquired on the ICU were reduced in the test group , as was oropharyngeal carriage . Neither vancomycin-resistant enterococci nor vancomycin-intermediate S. aureus were isolated from either surveillance or diagnostic sample s during the study period . The vancomycin costs were lower in the test group . This study demonstrates that oropharyngeal vancomycin , which controls intensive care unit‐acquired lower airway infections and secondary carriage due to methicillin-resistant Staphylococcus aureus , is cost-effective and safe in terms of vancomycin-resistant enterococci and vancomycin-intermediate Staphylococcus aureus Objective To evaluate the efficacy of bacterial filters ( BF ) to decrease pneumonia associated with mechanical ventilation ( MV ) . Design Prospect i ve , r and omized study . Setting A 24-bed medicosurgical intensive care unit in a 650-bed tertiary hospital . Patients A total of 230 patients who needed MV for > 24 hrs . Interventions A total of 114 patients were ventilated with BF and 116 without BF . Measurements Throat swab and tracheal aspirate were taken at the moment of admission and twice a week until discharge . We considered the following infectious events : pneumonia , respiratory infection , which comprises pneumonia or tracheobronchitis , and respiratory colonization – infection complex , which comprises respiratory infection or colonization . All infectious events were classified as endogenous or exogenous based on throat flora . Main Results Both groups of patients ( ventilated with and without filters ) were similar in age , sex , Acute Physiology and Chronic Health Evaluation II score , diagnostic group , days of MV , and mortality . There was no difference in the percentage of patients who developed pneumonia ( 24.56 % with BF and 21.55 % without BF ) , respiratory infection ( 33.33 % vs. 28.44 % ) , or colonization-infection ( 42.10 % vs. 43.96 % ) . The number of infectious events per 1000 days of MV were also similar in both groups : pneumonia ( 17.41 with BF and 16.26 without BF ) , respiratory infection ( 24.62 vs. 21.48 ) , and colonization-infection ( 36.63 vs. 36 ) . There were also no differences in incidence of infectious events by MV duration . Likewise , we did not find any differences in the number of exogenous events per 1000 days of MV : pneumonia , 2.40 with BF vs. 1.74 without BF ; colonization-infection , 4.20 vs. 4.05 . Conclusions Bacterial filters in ventilation circuits neither reduce the prevalence of respiratory infections associated with MV nor decrease exogenous infectious events ; thus , their usage is not necessary UNLABELLED Discussion of paranasal sinusitis as a nosocomial infection in the mechanically ventilated intensive care ( ICU ) patient has recently been intensified . Some authors have emphasized nasotracheal intubation as a possible pathogenetic pathway . The aim of this study was to investigate the impact of nasotracheal or orotracheal intubation on the development of sinusitis in ICU patients . METHODS In a prospect i ve study , we followed 44 patients who required mechanical ventilation ( greater than 24 h ) in the ICU because of prolonged recovery from abdominal , thoracic , or posttraumatic surgery . Twenty patients were intubated nasotracheally and 24 orotracheally . Assignment to the groups was r and om . All were provided with a nasogastric tube and initially treated with systemic antibiotics . They received local antimicrobial prophylaxis of the nose , oropharynx , and stomach . Daily a-scan examinations of the maxillary sinuses were performed from the day of admission to the ICU until extubation , tracheotomy , death , or transfer . The average observation period was 6.9 days in the oral group and 7.1 days in the nasal group . In the case of a pathologic finding , aspiration of the antral sinus was carried out . In this study sinusitis indicated a sonographic finding ; it did not necessarily imply a bacterial infection . RESULTS At the beginning of the observation period , 6 patients in the oral group and 4 in the nasal group already had a pathologic maxillary sinus finding . At the end , in 15 of 24 in the oral group and 19 of 20 in the nasal group unilateral or bilateral sinusitis could be demonstrated . Development of bilateral sinusitis ( 13/20 in the nasotracheal group , 8/24 in the orotracheal group ) was mainly observed after the appearance of unilateral sinusitis . The site corresponded to the site of the nasal tube in 65 % . Unilateral paranasal infection was observed in nasotracheally and orotracheally intubated patients after an average of 2.8 and 2.6 days , respectively , whereas bilateral sinusitis had an average time delay of 4.5 and 5.7 days . Aspiration of the maxillary sinus was performed in 22 of 34 cases with sinusitis . Pathogenic organisms could be demonstrated in 7 of 13 nasotracheally intubated patients but only 2 of 9 with orotracheal tubes . CONCLUSION We found that patients intubated orotracheally developed significantly less sinusitis than those intubated nasotracheally . Edema , local infection of the nasal mucosa , or mechanical obstruction of sinus drainage pathways by the tube are possible explanations . The fact that 63 % of orally intubated patients had a pathologic maxillary sinus finding as well suggests that in addition to other reasons , an increased central venous pressure , positive pressure ventilation , and the supine position must be regarded as predisposing factors that increase the incidence of sinusitis . We conclude that the conditions of critically ill patients predispose to the development of sinusitis . Nasotracheal intubation is to be regarded as an additional risk , and therefore oral intubation should be preferred Introduction Some guidelines to prevent ventilator-associated pneumonia ( VAP ) do not establish a recommendation for the preferential use of either heat and moisture exchangers ( HMEs ) or heated humidifiers ( HHs ) , while other guidelines clearly advocate the use of HMEs . The aim of this study was to determine the incidence of VAP associated with HHs or HMEs . Methods A r and omized study was conducted in the intensive care unit of a university hospital involving patients expected to require mechanical ventilation for > 5 days . Patients were assigned to two groups ; one group received HH and the other group received HME . Tracheal aspirate sample s were obtained on endotracheal intubation , then twice a week , and finally on extubation , in order to diagnose VAP . Throat swabs were taken on admission to the intensive care unit , then twice a week , and finally at discharge from the intensive care unit in order to classify VAP as primary endogenous , secondary endogenous , or exogenous . Results A total of 120 patients were assigned to HMEs ( 60 patients ) and HHs ( 60 patients ) ; 16 patients received mechanical ventilation for less than five days and were excluded from the analysis . Data analysis of the remaining 104 patients ( 53 HMEs and 51 HHs ) showed no significant differences between groups regarding sex , age , Acute Physiology and Chronic Health Evaluation II score , pre-VAP use of antibiotics , days on mechanical ventilation , and diagnosis group . VAP was found in eight of 51 ( 15.69 % ) patients in the HH group and in 21 of 53 ( 39.62 % ) patients in the HME group ( P = 0.006 ) . The median time free of VAP was 20 days ( 95 % confidence interval , 13.34–26.66 ) for the HH group and was 42 days ( 95 % confidence interval , 35.62–48.37 ) for the HME group ( P < 0.001 ) . Cox regression analysis showed the HME as a risk factor for VAP ( hazard rate , 16.2 ; 95 % confidence interval , 4.54–58.04 ; P < 0.001 ) . Conclusion The patients mechanically ventilated for more than five days developed a lower incidence of VAP with a HH than with a HME PURPOSE To compare turning by an oscillating bed to st and ard 2-hour turning . Outcomes were survival , length of stay ( LOS ) , duration of mechanical ventilation , and incidence of pneumonia . METHODS One hundred and three intensive care patients were r and omly assigned to st and ard turning or turning by an oscillating bed . Data , collected at baseline , daily for 7 days , and then three times weekly until study discharge , included demographics , initial Acute Physiology and Chronic Health Evaluation ( APACHE II ) score , ventilatory/gas exchange parameters , indicators of pneumonia , nursing measures , and chest roentgenograph . RESULTS There were no significant differences for LOS , duration of ventilation , nor incidence of pneumonia . Higher survival for subjects on the oscillating bed reached borderline significance ( P = .056 ) for subjects with APACHE II greater than or equal to 20 . Longitudinal data were analyzed using the r and om effects model . No differences in ventilatory or gas exchange parameters were identified . Among subjects who developed pneumonia there was a significantly higher respiratory score ( nursing acuity scale ) for subjects on the oscillating bed . CONCLUSIONS In selected critically ill patients oscillating therapy may improve survival and improve airway clearance . The frequency and degree of turning needed to prevent complications and improve outcome remains unclear . These newer beds should be used with discrimination so as to not increase hospital costs unnecessarily CONTEXT A recent trial showed that placing patients with acute lung injury in the prone position did not increase survival ; however , whether those results hold true for patients with hypoxemic acute respiratory failure ( ARF ) is unclear . OBJECTIVE To determine whether prone positioning improves mortality in ARF patients . DESIGN , SETTING , AND PATIENTS Prospect i ve , unblinded , multicenter controlled trial of 791 ARF patients in 21 general intensive care units in France using concealed r and omization conducted from December 14 , 1998 , through December 31 , 2002 . To be included , patients had to be at least 18 years , hemodynamically stable , receiving mechanical ventilation , and intubated and had to have a partial pressure of arterial oxygen ( PaO2 ) to fraction of inspired oxygen ( FIO2 ) ratio of 300 or less and no contraindications to lying prone . INTERVENTIONS Patients were r and omly assigned to prone position placement ( n = 413 ) , applied as early as possible for at least 8 hours per day on st and ard beds , or to supine position placement ( n = 378 ) . MAIN OUTCOME MEASURES The primary end point was 28-day mortality ; secondary end points were 90-day mortality , duration of mechanical ventilation , incidence of ventilator-associated pneumonia ( VAP ) , and oxygenation . RESULTS The 2 groups were comparable at r and omization . The 28-day mortality rate was 32.4 % for the prone group and 31.5 % for the supine group ( relative risk [ RR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.79 - 1.19 ; P = .77 ) . Ninety-day mortality for the prone group was 43.3 % vs 42.2 % for the supine group ( RR , 0.98 ; 95 % CI , 0.84 - 1.13 ; P = .74 ) . The mean ( SD ) duration of mechanical ventilation was 13.7 ( 7.8 ) days for the prone group vs 14.1 ( 8.6 ) days for the supine group ( P = .93 ) and the VAP incidence was 1.66 vs 2.14 episodes per 100- patients days of intubation , respectively ( P = .045 ) . The PaO2/FIO2 ratio was significantly higher in the prone group during the 28-day follow-up . However , pressure sores , selective intubation , and endotracheal tube obstruction incidences were higher in the prone group . CONCLUSIONS This trial demonstrated no beneficial outcomes and some safety concerns associated with prone positioning . For patients with hypoxemic ARF , prone position placement may lower the incidence of VAP BACKGROUND Ventilator-associated pneumonia ( VAP ) is an important cause of morbidity and mortality in ventilated critically ill patients . Despite a large amount of research evidence , the optimal diagnostic and treatment strategies for VAP remain controversial . PURPOSE The aim of this study was to develop evidence -based clinical practice guidelines for the diagnosis and treatment of VAP . Data sources include Medline , EMBASE , Cumulative Index to Nursing and Allied Health Literature , and the Cochrane Data base of Systematic Review s and Register of Controlled Trials . STUDY SELECTION The authors systematic ally search ed for all relevant r and omized controlled trials and systematic review s on the diagnosis and treatment of VAP in mechanically ventilated adults that were published from 1980 to October 1 , 2006 . DATA EXTRACTION Independently and in duplicate , the panel critically appraised each published trial . The effect size , confidence intervals , and homogeneity of the results were scored using predefined definitions . The full guideline development panel arrived at a consensus for scores on safety , feasibility , and economic issues . LEVELS OF EVIDENCE Based on the scores for each topic , the following statements of recommendation were used : recommend , consider , do not recommend , and no recommendation because of insufficient or conflicting evidence . DATA SYNTHESIS For the diagnosis of VAP in immunocompetent patients , we recommend that endotracheal aspirates with nonquantitative cultures be used as the initial diagnostic strategy . When there is a suspicion of VAP , we recommend empiric antimicrobial therapy ( in contrast to delayed or culture directed therapy ) and appropriate single agent antimicrobial therapy for each potential pathogen as empiric therapy for VAP . Choice of antibiotics should be based on patient factors and local resistance patterns . We recommend that an antibiotic discontinuation strategy be used in patients who are treated of suspected VAP . For patients who receive adequate initial antibiotic therapy , we recommend 8 days of antibiotic therapy . We do not recommend nebulized endotracheal tobramycin or intratracheal instillation of tobramycin for the treatment of VAP . CONCLUSION We present evidence -based recommendations for the diagnosis and treatment of VAP . Implementation of these recommendations into clinical practice may lessen the morbidity and mortality of patients who develop VAP BACKGROUND Risk factors for nosocomial pneumonia , such as gastro-oesophageal reflux and subsequent aspiration , can be reduced by semirecumbent body position in intensive-care patients . The objective of this study was to assess whether the incidence of nosocomial pneumonia can also be reduced by this measure . METHODS This trial was stopped after the planned interim analysis . 86 intubated and mechanically ventilated patients of one medical and one respiratory intensive-care unit at a tertiary-care university hospital were r and omly assigned to semirecumbent ( n=39 ) or supine ( n=47 ) body position . The frequency of clinical ly suspected and microbiologically confirmed nosocomial pneumonia ( clinical plus quantitative bacteriological criteria ) was assessed in both groups . Body position was analysed together with known risk factors for nosocomial pneumonia . FINDINGS The frequency of clinical ly suspected nosocomial pneumonia was lower in the semirecumbent group than in the supine group ( three of 39 [ 8 % ] vs 16 of 47 [ 34 % ] ; 95 % CI for difference 10.0 - 42.0 , p=0.003 ) . This was also true for microbiologically confirmed pneumonia ( semirecumbent 2/39 [ 5 % ] vs supine 11/47 [ 23 % ] ; 4.2 - 31.8 , p=0.018 ) . Supine body position ( odds ratio 6.8 [ 1.7 - 26.7 ] , p=0.006 ) and enteral nutrition ( 5.7 [ 1.5 - 22.8 ] , p=0.013 ) were independent risk factors for nosocomial pneumonia and the frequency was highest for patients receiving enteral nutrition in the supine body position ( 14/28 , 50 % ) . Mechanical ventilation for 7 days or more ( 10.9 [ 3.0 - 40.4 ] , p=0.001 ) and a Glasgow coma scale score of less than 9 were additional risk factors . INTERPRETATION The semirecumbent body position reduces frequency and risk of nosocomial pneumonia , especially in patients who receive enteral nutrition . The risk of nosocomial pneumonia is increased by long- duration mechanical ventilation and decreased consciousness BACKGROUND The provision of nutritional support for patients in intensive care units ( ICUs ) varies widely both within and between institutions . We tested the hypothesis that evidence -based algorithms to improve nutritional support in the ICU would improve patient outcomes . METHODS A cluster-r and omized controlled trial was performed in the ICUs of 11 community and 3 teaching hospitals between October 1997 and September 1998 . Hospital ICUs were stratified by hospital type and r and omized to the intervention or control arm . Patients at least 16 years of age with an expected ICU stay of at least 48 hours were enrolled in the study ( n = 499 ) . Evidence -based recommendations were introduced in the 7 intervention hospitals by means of in-service education sessions , reminders ( local dietitian , posters ) and academic detailing that stressed early institution of nutritional support , preferably enteral . RESULTS Two hospitals crossed over and were excluded from the primary analysis . Compared with the patients in the control hospitals ( n = 214 ) , the patients in the intervention hospitals ( n = 248 ) received significantly more days of enteral nutrition ( 6.7 v. 5.4 per 10 patient-days ; p = 0.042 ) , had a significantly shorter mean stay in hospital ( 25 v. 35 days ; p = 0.003 ) and showed a trend toward reduced mortality ( 27 % v. 37 % ; p = 0.058 ) . The mean stay in the ICU did not differ between the control and intervention groups ( 10.9 v. 11.8 days ; p = 0.7 ) . INTERPRETATION Implementation of evidence -based recommendations improved the provision of nutritional support and was associated with improved clinical outcomes Objective To determine whether extended use ( 7 days ) would affect the efficiency on heat and water preservation of a hydrophobic condenser humidifier as well as the rate of ventilation-acquired pneumonia , compared with 1 day of use . Design Prospect i ve , controlled , r and omized , not blinded , clinical study . Setting Twelve-bed intensive care unit of a university hospital . Patients One hundred and fifty-five consecutive patients undergoing mechanical ventilation for ≥48 hrs . Interventions After r and omization , patients were allocated to one of the two following groups : a ) heat and moisture exchangers ( HMEs ) changed every 24 hrs ; b ) HMEs changed only once a week . Devices in both groups could be changed at the discretion of the staff when signs of occlusion or increased resistance were identified . Measurements and Main Result Efficient airway humidification and heating were assessed by clinical variables ( numbers of tracheal suctionings and instillations required , peak and mean airway pressures ) . The frequency rates of bronchial colonization and ventilation-acquired pneumonia were evaluated by using clinical and microbiological criteria . Endotracheal tube occlusion , ventilatory support variables , duration of mechanical ventilation , length of intensive care , acquired multiorgan dysfunction , and mortality rates also were recorded . The two groups were similar at the time of r and omization . Endotracheal tube occlusion never occurred . In the targeted population ( patients ventilated for ≥7 days ) , the frequency rate of ventilation-acquired pneumonia was 24 % in the HME 1-day group and 17 % in the HME 7-day group ( p > .05 , not significant ) . Ventilation-acquired pneumonia rates per 1000 ventilatory support days were 16.4/1000 in the HME 1-day group and 12.4/1000 in the HME 7-day group ( p > .05 , not significant ) . No statistically significant differences were found between the two groups for duration of mechanical ventilation , intensive care unit length of stay , acquired organ system derangements , and mortality rate . There was indirect evidence of very little , if any , change in HME resistance . Conclusions Changing the studied hydrophobic HME after 7 days did not affect efficiency , increase resistance , or altered bacterial colonization . The frequency rate of ventilation-acquired pneumonia was also unchanged . Use of HMEs for > 24 hrs and up to 7 days is safe The aim of this study was to compare the effect of closed versus open endotracheal suction systems on the development of ventilator-associated pneumonia ( VAP ) . A prospect i ve , r and omized , controlled trial was performed in a medical intensive care unit ( MICU ) of a university hospital in patients who received mechanical ventilation for more than 48 h. Patients were r and omized to receive endotracheal suction with either closed catheters ( closed suction group ; N-41 ) or single-use catheters ( open suction group ; N=37 ) . Cultures were taken from the ventilator tubing of 42 patients to determine the rate of colonization . There was no difference between the groups in terms of the frequency of development of VAP , mortality in the MICU , length of MICU stay and duration of mechanical ventilation . Thirteen patients in the open suction group and 16 patients in the closed suction group became colonized ( P=0.14 ) . The colonization rates by Acinetobacter spp . and Pseudomonas aeruginosa were more frequent in the closed suction group than in the open suction group ( P<0.01 and P=0.04 , respectively ) . In conclusion , closed endotracheal suction result ed in increased colonization rates of ventilator tubing with multi drug-resistant micro-organisms but did not increase the development of VAP and MICU outcome compared with open endotracheal suction During a 12‐month period , 264 patients with multiple injuries who required mechanical ventilation were admitted to the surgical intensive care unit . One hundred twenty patients ( 46 % ) were disengaged from the ventilator , and 38 patients ( 14 % ) died . Of the remaining 106 patients ( 40 % ) 51 patients ( group I ) were to receive tracheostomy within 1 to 7 days , and 55 patients ( group II ) underwent late ( 8 or more days after admission ) tracheostomy . Multiple variables in four categories ( admission , operative , ventilatory , and outcome ) were analyzed prospect ively to define the impact that early tracheostomy had on duration of mechanical ventilation , intensive care stay , and hospital stay . Morbidity and mortality rates of the procedures were assessed . Early tracheostomy , in a homogeneous group of critically ill patients , is associated with a significant decrease in duration of mechanical ventilation , as well as shorter intensive care unit and hospital stays , compared with translaryngeal endotracheal intubation . There were no deaths attributable to tracheostomy , and overall morbidity of the procedures was 4 % . We conclude that early tracheostomy has an overall risk equivalent to that of endotracheal intubation . Furthermore , early tracheostomy shortens days on the ventilator and intensive care unit and hospital days and should be considered for patients in the intensive care unit at risk for more than 7 days of intubation BACKGROUND When liver transplant c and i date s and recipients suffer from pulmonary complications of immobility , the results can be life-threatening . Continuous lateral rotation therapy has been reported to decrease complications of immobility . OBJECTIVES To determine whether continuous lateral rotation therapy decreases the duration of mechanical ventilation , intensive care unit length of stay , incidence or resolution of atelectasis , incidence or onset time of lower respiratory tract infection and pneumonia . METHODS Sixty-nine subjects admitted to a liver transplant intensive care unit at a university teaching hospital were r and omly assigned to continuous lateral rotation therapy or a stationary bed . All subjects were mechanically ventilated for 24 hours and had a Glasgow Coma Scale score of 11 or less upon admission to the study . Subjects were followed until out of bed , unable to rotate for 3 consecutive days , or transferred from the intensive care unit . Data and chest roentgenogram results were collected on admission and daily during the study . Sputum culture results were obtained if available as part of normal patient care . RESULTS Incidence of lower respiratory tract infection was significantly lower and length of time to occurrence of lower respiratory tract infection was significantly longer in the continuous lateral rotation therapy group than in the stationary bed group . CONCLUSIONS Although continuous lateral rotation therapy did not affect duration of mechanical ventilation , length of stay , or incidence of atelectasis , it was effective in decreasing the incidence of , and increasing onset time to , lower respiratory tract infection in the liver transplantation population RATIONALE Ventilator-associated pneumonia ( VAP ) is the most frequently occurring nosocomial infection associated with increased morbidity and mortality . Although oral decontamination with antibiotics reduces incidences of VAP , it is not recommended because of potential selection of antibiotic-resistant pathogens . We hypothesized that oral decontamination with either chlorhexidine ( CHX , 2 % ) or CHX/colistin ( CHX/COL , 2%/2 % ) would reduce and postpone development of VAP , and oral and endotracheal colonization . OBJECTIVES To determine the effect of oral decontamination with CHX or CHX/COL on VAP incidence and time to development of VAP . METHODS Consecutive patients needing mechanical ventilation for 48 h or more were enrolled in a r and omized , double-blind , placebo-controlled trial with three arms : CHX , CHX/COL , and placebo ( PLAC ) . Trial medication was applied every 6 h into the buccal cavity . Oropharyngeal swabs were obtained daily and quantitatively analyzed for gram-positive and gram-negative microorganisms . Endotracheal colonization was monitored twice weekly . RESULTS Of 385 patients included , 130 received PLAC , 127 CHX and 128 CHX/COL . Baseline characteristics were comparable . The daily risk of VAP was reduced in both treatment groups compared with PLAC : 65 % ( hazard ratio [HR]=0.352 ; 95 % confidence interval [ CI ] , 0.160 , 0 . 791 ; p=0.012 ) for CHX and 55 % ( HR=0.454 ; 95 % CI , 0.224 , 0 . 925 ; p=0.030 ) for CHX/COL . CHX/COL provided significant reduction in oropharyngeal colonization with both gram-negative and gram-positive microorganisms , whereas CHX mostly affected gram-positive microorganisms . Endotracheal colonization was reduced for CHX/COL patients and to a lesser extent for CHX patients . No differences in duration of mechanical ventilation , intensive care unit stay , or intensive care unit survival could be demonstrated . CONCLUSIONS Topical oral decontamination with CHX or CHX/COL reduces the incidence of VAP Objective We investigated the efficacy of locally applied nasal decongestant agents and corticosteroids for preventing nosocomial maxillary sinusitis in mechanically ventilated patients with multiple trauma . Design and setting A prospect i ve , open-label r and omized study in two intensive care units ( ICUs ) . Patients 79 consecutive multiple trauma patients admitted to the ICU who were expected to be mechanically ventilated for more than 3 days . Interventions Patients were r and omly assigned to receive either a combination of a locally applied nasal decongestant agents : 2 drops twice/day of xylometazoline nasal solution 0.1 % and 100 μg budesonide ( NDCA group , n = 39 ) or placebo ( control group , n = 40 ) . Measurements For the diagnosis of radiological maxillary sinusitis patients underwent paranasal computed tomography within 48 h of admission and thereafter every 4–7 days . Infectious maxillary sinusitis was diagnosed by microbiological analysis of fluid aspirated after transnasal puncture of maxillary sinuses . Results Radiological maxillary sinusitis was detected in 54 % of patients in the NDCA group ( n = 21 ) but in 82 % of controls ( p < 0.01 ) , and infectious maxillary sinusitis in 8 % of the NDCA group ( n = 3 ) but in 20 % of controls ( n = 8 ; p = 0.11 ) . The most common pathogen micro-organisms identified from maxillary aspirates were Acinetobacter ( 32 % ) followed by anaerobes ( 21 % ) . Conclusion Our results indicate that the combination of locally applied xylometazoline hydrochloride and budesonide reduces the incidence of radiological maxillary sinusitis and may reduce also that of nosocomial maxillary sinusitis in mechanically ventilated patients with multiple trauma The incidence of infectious maxillary sinusitis ( IMS ) and its clinical relevance was prospect ively studied in 162 consecutive critically ill patients who were mechanically ventilated for a period longer than 7 d. All had a paranasal computed tomographic ( CT ) scan within 48 h of admission and were divided into three groups according to the radiologic aspect of their maxillary sinuses : Group 1 = normal maxillary sinuses ( n = 40 ) , Group 2 = maxillary mucosal thickening ( n = 26 ) , Group 3 = radiologic maxillary sinusitis ( RMS ) defined as the presence of an air fluid level and /or opacification of maxillary sinuses ( n = 96 ) . Group 1 patients were r and omized between nasal and oral endotracheal intubation with a gastric intubation performed via the same route and had a second paranasal CT scan 7 d later . Endotracheal and gastric tubes were left in their original position in Group 2 patients and a second paranasal CT scan was performed 7 d later . All patients of Group 3 underwent a transnasal puncture for bacteriologic analysis of maxillary sinus content . Forty-five spontaneously breathing patients served as a control group . In all patients with RMS , the occurrence of bronchopneumonia ( BPN ) was prospect ively assessed for 7 d following the initial CT scan . Upon inclusion , only 25 % of the patients had normal maxillary sinuses whereas all patients in the control group had normal paranasal CT scans . After 7 d , 46 % of Group 2 patients had evidence of RMS . Risk factors for RMS were nasal placement and duration of endotracheal and gastric intubation . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To analyze the efficacy of periodically changing ventilator circuits for decreasing the rate of ventilator-associated pneumonia when a heat and moisture exchanger ( HME ) is used for humidification . The Centers for Disease Control and Prevention recommended not changing the circuits periodically . DESIGN R and omized , controlled trial conducted between April 2001 and August 2002 . SETTING A 24-bed , medical-surgical intensive care unit in a 650-bed , tertiary-care hospital . PATIENTS All patients requiring mechanical ventilation during more than 72 hours from April 2001 to August 2002 . INTERVENTIONS Patients were r and omized into two groups : ( 1 ) ventilation with change of ventilator circuits every 48 hours and ( 2 ) ventilation with no change of circuits . Throat swabs were taken on admission and twice weekly until discharge to classify pneumonia as endogenous or exogenous . RESULTS Three hundred four patients ( 143 from group 1 and 161 from group 2 ) with similar characteristics ( age , gender , Acute Physiology and Chronic Health Evaluation II score , diagnostic group , and mortality ) were analyzed . There was no significant difference in the rate of pneumonia between the groups ( 23.1 % vs 23.0 % and 15.5 vs 14.8 per 1,000 ventilator-days ) . There was no significant difference in the incidence of exogenous pneumonia per 1,000 days of mechanical ventilation ( 1.71 vs 1.25 ) . There was no difference in the distribution of microorganisms causing pneumonia . CONCLUSIONS Circuit change using an HME for humidification does not decrease pneumonia and represents an unnecessary cost STUDY OBJECTIVES To evaluate the safety and efficacy of aerosolized ceftazidime for prevention of ventilator-associated pneumonia ( VAP ) and to evaluate the effects of the drug on the proinflammatory response . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled clinical trial . SETTING University teaching hospital . PATIENTS Forty critically ill trauma patients at high risk for VAP Intervention . Within 48 hours of admission to the intensive care unit ( ICU ) , patients were r and omly assigned to receive aerosolized ceftazidime 250 mg every 12 hours or placebo ( normal saline ) for up to 7 days . Bronchoalveolar concentrations of tumor necrosis factor-alpha ( TNF-alpha ) , interleukin (IL)-1beta , IL-6 , and IL-8 were determined at baseline and the end of therapy ( days 4 - 7 ) . MEASUREMENTS AND MAIN RESULTS The frequency of VAP in patients receiving aerosolized ceftazidime was 73 % lower than that in patients receiving placebo at ICU day 14 ( 15 % vs 55 % , p = 0.021 ) , and 54 % lower for the entire ICU stay ( 30 % vs 65 % , p = 0.022 ) . No clinical ly significant changes in bacterial culture and sensitivity patterns were observed . No adverse events from aerosolized ceftazidime were reported . Pulmonary TNF-alpha , IL-beta , and IL-8 concentrations were attenuated in the ceftazidime group compared with those in the placebo group ( p < 0.001 , p = 0.02 , and p = 0.003 ) . The frequency of VAP was related directly to changes in TNF-alpha and IL-beta ( p < 0.001 , p = 0.02 ) . CONCLUSIONS Aerosolized ceftazidime decreased the frequency of VAP in critically ill trauma patients , without adversely affecting ICU flora . Aerosolized ceftazidime also may attenuate the proinflammatory response in the lung BACKGROUND There is increasing concern about the quality , reliability , and independence of practice guidelines . Because no information is available on the method ological quality of the guidelines developed by specialty societies , we undertook a survey on those published in peer- review ed journals . METHODS Practice guidelines produced by specialty societies and published in English between January , 1988 , and July , 1998 , where identified through MEDLINE . Their quality was assessed in terms of whether they reported : the type of professionals and stakeholders involved in the development process ; the strategy to identify primary evidence ; and an explicit grading of recommendations according to the quality of supporting evidence . FINDINGS Overall , 431 guidelines were eligible for the study . Most did not meet the criteria : 67 % did not report any description of the type of stakeholders , 88 % gave no information on search es for published studies , and 82 % did not give any explicit grading of the strength of recommendations . There was improvement over time for search es ( from 2 % to 18 % , p<0.001 ) and explicit grading of evidence ( from 6 % to 27 % , p<0.001 ) . All three criteria for quality were met in only 22 ( 5 % ) guidelines . INTERPRETATION Despite improvement over time , the quality of practice guidelines developed by specialty societies is unsatisfactory . Explicit method ological criteria for the production of guidelines shared among public agencies , scientific societies , and patients ' associations need to be set up . Common st and ards of reporting , following the same principles that led to the CONSORT statement for r and omised clinical trials , should be promoted Abstract . Objective : Comatose patients frequently exhibit pulmonary function worsening , especially in cases of pulmonary infection . It appears to have a deleterious effect on neurologic outcome . We therefore conducted a r and omized trial to determine whether daily prone positioning would prevent lung worsening in these patients . Design : Prospect i ve , r and omized , controlled study . Setting : Sixteen-bed intensive care unit . Patients : Fifty-one patients who required invasive mechanical ventilation because of coma with Glascow coma scores of 9 or less . Interventions : In the prone position ( PP ) group : prone positioning for 4 h once daily until the patients could get up to sit in an armchair ; in the supine position ( SP ) group : supine positioning . Measurements and results : The primary end point was the incidence of lung worsening defined by an increase in the Lung Injury Score of at least 1 point since the time of r and omization . The secondary end point was the incidence of ventilator-associated pneumonia ( VAP ) . A total of 25 patients were r and omly assigned to the PP group and 26 patients to the SP group . The characteristics of the patients from the two groups were similar at r and omization . The incidence of lung worsening was lower in the PP group ( 12 % ) than in the SP group ( 50 % ) ( p=0.003 ) . The incidence of VAP was 20 % in the PP group and 38.4 % in the SP group ( p=0.14 ) . There was no serious complication attributable to prone positioning , however , there was a significant increase of intracranial pressure in the PP . Conclusion : In a selected population of comatose ventilated patients , daily prone positioning reduced the incidence of lung worsening STUDY OBJECTIVE To determine the safety and cost-effectiveness of mechanical ventilation with an extended-use hygroscopic condenser humidifier ( Duration ; Nellcor Puritan-Bennett ; Eden Prairie , Minn ) compared with mechanical ventilation with heated-water humidification . DESIGN Prospect i ve r and omized clinical trial . SETTING Medical and surgical ICUs of Barnes-Jewish Hospital , St. Louis , a university-affiliated teaching hospital . PATIENTS Three hundred ten consecutive qualified patients undergoing mechanical ventilation . INTERVENTIONS Patients requiring mechanical ventilation were r and omly assigned to receive humidification with either an extended-use hygroscopic condenser humidifier ( for up to the first 7 days of mechanical ventilation ) or heated-water humidification . MEASUREMENTS Occurrence of ventilator-associated pneumonia , endotracheal tube occlusion , duration of mechanical ventilation , lengths of intensive care and hospitalization , acquired multiorgan dysfunction , and hospital mortality . RESULTS One hundred sixty-three patients were r and omly assigned to receive humidification with an extended-use hygroscopic condenser humidifier , and 147 patients were r and omly assigned to receive heated-water humidification . The two groups were similar at the time of r and omization with regard to demographic characteristics , ICU admission diagnoses , and severity of illness . Risk factors for the development of ventilator-associated pneumonia were also similar during the study period for both treatment groups . Ventilator-associated pneumonia was seen in 15 ( 9.2 % ) patients receiving humidification with an extended-use hygroscopic condenser humidifier and in 15 ( 10.2 % ) patients receiving heated-water humidification ( relative risk , 0.90 ; 95 % confidence interval=0.46 to 1.78 ; p=0.766 ) . No statistically significant differences for hospital mortality , duration of mechanical ventilation , lengths of stay in the hospital ICU , or acquired organ system derangements were found between the two treatment groups . No episode of endotracheal tube occlusion occurred during the study period in either treatment group . The total cost of providing humidification was $ 2,605 for patients receiving a hygroscopic condenser humidifier compared with $ 5,625 for patients receiving heated-water humidification . CONCLUSION Our findings suggest that the initial application of an extended-use hygroscopic condenser humidifier is a safe and more cost-effective method of providing humidification to patients requiring mechanical ventilation compared with heated-water humidification BACKGROUND To evaluate efficacy of mupirocin ointment nasal application in prevention of MRSA ventilatory associated pneumonia ( VAP ) . METHODS DESIGN prospect i ve , double-blind , r and omized , clinical trial . PATIENTS 48 consecutive intubated patients admitted in the Intensive Care Unit during a three month period . SETTING University of Florence ; Intensive Care . INTERVENTIONS R and omized application of 2 ml of Mupirocin ointment three times a day for three days ( Group A ; n = 24 ) or placebo ( Group B n = 24 ) . STATISTIC Chi 2 or Fisher exact test . MEASUREMENTS Bacteriologic evaluation of nasal carriage at admission in ICU , and after 3 days of prevention ; evaluation of bacteriology of bronchial aspirate in the case of symptoms of ventilatory associated pneumonia . RESULTS AND CONCLUSIONS Relative risk of nasal carriage by pathological bacterial strains is 7.2 times in hospitalized patients more than in home patients ( 18/25 vs 7/23 ) ; MRSA nasal carriage is present at admission on 20 % of hospitalized patients . Nasal carriage of Staphylococcus strains is reduced of 90 % by Mupirocin application but is reduced only of 50 % by placebo application ( p < 0.05 ) . In Group B , VAP occurred in 5 patients vs 3 of Group A ; the more frequent incidence of VAP in group B is due to MRSA infection ( p < 0.01 ) and it is related to MRSA nasal carriage Objective : To assess the impact of nosocomial infection on the mortality rate in an intensive care unit ( ICU ) . Design : Prospect i ve cohort study . Setting : The ICU of the University of Granada Hospital in Spain . Patients : All patients ( n=279 ) admitted for ≥48 hrs at the ICU between December 1986 and April 1988 . Measurements : Nosocomial infections were diagnosed according to Study on the Efficacy of Nosocomial Infection Control ( SENIC ) and Centers for Disease Control criteria . Patient severity on admission ( using Acute Physiology and Chronic Health Evaluation ( APACHE II ) and Therapeutic Intensity Scoring Systems were also used . Results : Mortality risk was 2.48 times higher in patients with a nosocomial infection than in noninfected patients . Relative risk of mortality in nosocomially infected patients was higher in young and less severely ill patients , in those patients with respiratory diseases , and in those patients with longer ICU stays . Logistic stepwise regression analysis , adjusting for several confounding factors ( affected organ system , APACHE II score , and therapeutic intensity ) , showed that the risk of death in nosocomially infected patients was 2.1 times greater ( 95 % confidence interval = 1.0 to 4.41 ) than in patients without such infection . Conclusions : Nosocomial infection increases the risk of death . The effect is stronger in younger and less severely ill patients . ( Crit Care Med 1994 ; 22:55‐60 Inspired gases must be warmed and humidified during mechanical ventilation . In a prospect i ve r and omized study we compared the performance of a heated humidifier ( HH ) ( Draegger Aquaport ) and a heat and moisture exchanger ( HME ) ( Pall Filter BB 2215 ) . A total of 116 patients requiring mechanical ventilation ( Servo 900C Siemens ) were enrolled into the study and were r and omly assigned to 2 groups . Patients in group I were ventilated with a traditional breathing circuit with HH and patients in group II using a simplified circuit with HME . Pre-existing and hospital acquired atelectasis and pneumonia , occurrence of endotracheal tube ( ET ) occlusion and ventilatory parameters ( respiratory rate , tidal volume ) were studied . No statistical difference was found between groups for each parameter except the greater frequency of ET occlusions in the II group ( 0/61 vs 9/55 ) ( p=0.0008 ) . Pall Filter ( PF ) , a hydrophobic filter , humidifies the dry gases from the condensed water which is put down on the HME surfaces during cooling of saturated expired gases . This purely physical property is linked to the magnitude of the thermic gradient between the expired pried gase and the ambiant temperture . Performance impairment of PF in our study might be due to high ambiant temperature in the intensive care unit ( usually around 28 ° C ) which reduces thermic gradient and water exchanges . We conclude that efficiency of PF may be weak in some conditions of ambiant temperature OBJECTIVE To evaluate the current use of strategies to prevent ventilator-associated pneumonia ( VAP ) and to identify interventions to target for quality -improvement initiatives . DESIGN Cross-sectional national survey . SETTING Canadian intensive care units ( ICUs ) with at least 8 beds . PATIENTS Seven hundred and two patients in 66 ICUs in 10 provinces in Canada . INTERVENTIONS None . MEASUREMENTS AND RESULTS The Canadian Critical Care Trials Group recently developed VAP prevention guidelines . Before these guidelines were disseminated , we documented the extent to which these recommendations were followed in practice by using 3 methods : survey of ICU directors , prospect i ve observation of patients on one day , and retrospective review of patient charts for a 12-day period . According to ICU directors , ventilator circuits were changed only for new patients or if the circuit was soiled in 7 of 66 ICUs ( 10 % ) , heat and moisture exchangers were used routinely in 53 of 66 ICUs ( 80 % ) , and closed-suction catheter systems were used in 58 of 66 ICUs ( 88 % ) . Neither subglottic secretion drainage tubes nor prophylactic antibiotics for VAP were used at all . Of the entire cohort of 702 patients , the average degree of elevation of the head of the bed was 29.9 degrees ( range , 0 degrees -90 degrees ) and 22 of 702 ( 3.1 % ) were observed to be on a kinetic bed . Of the 459 patients receiving any form of mechanical ventilation , 56 ( 12.2 % ) were receiving noninvasive or mask ventilation , 262 ( 57.1 % ) were orally intubated , 9 ( 1.9 % ) were nasally intubated , and 132 ( 28.8 % ) had received a tracheostomy . Of the 423 patients who received nutrition support , 373 ( 88.2 % ) received enteral nutrition . Small bowel feeding tubes were used during 16.4 % of study days on enteral feeds and sucralfate was prescribed for 1.7 % of study days . CONCLUSIONS Significant opportunities exist to improve VAP prevention practice s in Canada . These strategies include decreasing the frequency of ventilator circuit changes , and increasing the use of non-invasive ventilation , subglottic secretion drainage endotracheal tubes , kinetic bed therapy , small bowel feedings , and elevation of the head of the bed OBJECTIVE We hypothesized that a program of prospect i ve intensive surveillance for ventilator-associated pneumonia ( VAP ) and concomitant implementations of multimodal , multidisciplinary preventive and intervention strategies would result in a reduction in the incidence of VAP and would be cost-effective . SETTING Medical and surgical intensive care units ( ICUs ) in a university teaching hospital . INTERVENTIONS All ventilated patients in the medical and surgical ICUs were monitored for VAP from January 1997 through December 1998 . Interventions including elevation of the head of the bed , use of sterile water and replacement of stopcocks with enteral valves for nasogastric feeding tubes , and prolongation of changing of in-line suction catheters from 24 hours to as needed were implemented . RESULTS The rates of VAP decreased by 10.8/1,000 ventilator-days in the medical ICU ( CI95 , 4.65 - 16.91 ) and by 17.2/1,000 ventilator-days in the surgical ICU ( CI95 , 2.85 - 31.56 ) when they were compared for 1997 and 1998 . With the use of the estimated cost of a VAP of dollars 4,947 from the literature , the reduction result ed in cost savings of dollars 178,092 and dollars 148,410 in the medical and surgical ICUs , respectively , for a total of dollars 326,482 . In addition , dollars 25,497 was saved due to the lengthening of the time for the change of in-line suction catheters , result ing in a cost savings of dollars 351,979 . This total cost savings of dollars 351,979 minus the cost of enteral valves of dollars 2,100 result ed in total net savings of dollars 349,899 . CONCLUSION Intensive surveillance and interventions targeted at ventilated patients result ed in reduction of VAP and appeared to be cost-effective Nosocomial maxillary sinusitis during mechanical ventilation may cause life-threatening complications in ICU patients . The aim of this prospect i ve study was to compare the incidence of maxillary sinusitis according to the route of intubation . 111 consecutive adult patients ( mean age : 53 , mean SAPS : 12 ) were r and omly assigned to receive either orotracheal ( n=53 ) or nasotracheal ( n=58 ) intubation . All had a nasogastric feeding tube . Patients with head trauma or mechanical ventilation for less than 48h were excluded . Sinusitis diagnosis was made by radiography ( waters ' view ) at the bedside . The two groups were similar in age , SAPS , duration of ventilation . Maxillary sinusitis occurred in 1/53 ( 1.8 % ) of the orotracheal group ( on the nasogastric tube side ) , and in 25/58 ( 43.1 % ) of the nasotracheal group ( 7 on the nasogastric tube side , 11 on the endotracheal tube side , 7 bilateral;p<0.001 ) . Nine of the 26 cases of sinusitis were initially treated by sinus drainage because of signs of infection ( 3 failures ) and the 17 others were treated by tube removal . This procedure proved successful in 12 out of 17 cases but secondary drainage was performed in 5 cases ( 1 failure ) . Incidents related to the route for long-term intubation were significantly ( p<0.001 ) more frequent in the orotracheal group ( 8/53 vs 2/58 ) , however no patient died because of them . In this study , long-term orotracheal intubation reduced significantly the incidence of maxillary sinusitis in comparison with nasotracheal intubation Eighty-four intubated , mechanically ventilated patients were prospect ively evaluated for incidences of colonization and nosocomial pneumonias dependent on whether they received endotracheal suctioning by an “ open ” suction method vs. “ closed ” suction ( Trach Care ™ Closed Suction System ) method . Results show that closed suctioning is associated with a significant ( 67 % vs. 39 % p < .02 ) increase in colonization compared with open suctioning . However , difference in the incidence of nosocomial pneumonia was not significantly ( 26 % vs. 29 % ) different between closed and open suctioning . Differences in severity of illness ( Acute Physiology and Chronic Health Evaluation II and Therapeutic Intervention Scoring System ) , age , sex , presence of NG tubes , use of H2 antagonists or antacids , use of antibiotics , and history of smoking were all nonsignificant . Survival analysis demonstrated that the probability of survival without developing nosocomial pneumonia was greater among closed-suctioning patients vs. open-suctioned patients ( p < .03 ) . This study shows that suctioning performed via the Trach Care closed-suction system increases the incidence of colonization but not the incidence of nosocomial pneumonia , and may actually decrease mortality when compared with open-suction systems Objective : The timing of tracheotomy in patients requiring mechanical ventilation is unknown . The effects of early percutaneous dilational tracheotomy compared with delayed tracheotomy in critically ill medical patients needing prolonged mechanical ventilation were assessed . Design : Prospect i ve , r and omized study . Setting : Medical intensive care units . Patients : One hundred and twenty patients projected to need ventilation > 14 days . Interventions : None . Measurements and Main Results : Patients were prospect ively r and omized to either early percutaneous tracheotomy within 48 hrs or delayed tracheotomy at days 14–16 . Time in the intensive care unit and on mechanical ventilation and the cumulative frequency of pneumonia , mortality , and accidental extubation were documented . The airway was assessed for oral , labial , laryngeal , and tracheal damage . Early group showed significantly less mortality ( 31.7 % vs. 61.7 % ) , pneumonia ( 5 % vs. 25 % ) , and accidental extubations compared with the prolonged translaryngeal group ( 0 vs. 6 ) . The early tracheotomy group spent less time in the intensive care unit ( 4.8 ± 1.4 vs. 16.2 ± 3.8 days ) and on mechanical ventilation ( 7.6 ± 2.0 vs. 17.4 ± 5.3 days ) . There was also significantly more damage to mouth and larynx in the prolonged translaryngeal intubation group . Conclusions : This study demonstrates that the benefits of early tracheotomy outweigh the risks of prolonged translaryngeal intubation . It gives credence to the practice of subjecting this group of critically ill medical patients to early tracheotomy rather than delayed tracheotomy BACKGROUND To see if early tracheostomy ( fifth day ) reduces duration of mechanical ventilation , ICU stay , incidence of pneumonia and mortality in comparison with prolonged intubation ( PI ) in patients with head injury . METHODS Patients were prospect ively included in this study if they met the following criteria : isolated head injury , Glasgow coma scale ( GCS ) score < or = 8 on first and fifth day , with cerebral contusion on CT scan . On the fifth day , r and omization was done in two groups : early tracheostomy group ( T group , n = 31 ) and prolonged endotracheal intubation group ( I group , n = 31 ) . We evaluated total time of mechanical ventilation , ICU stay , pneumonia incidence and mortality . Complications related to each technique were noted . Analysis of data were performed using Yates and Kruskall Walis tests . p < 0.05 was considered significant . RESULTS The two groups were comparable in term of age , sex , and Simplified Acute Physiologic Score ( SAPS ) . The mean time of mechanical ventilatory support was shorter in T group ( 14.5 + /- 7.3 ) versus I group ( 17.5 + /- 10.6 ) ( p = 0.02 ) . After pneumonia was diagnosed , mechanical ventilatory time was 6 + /- 4.7 days for ET group versus 11.7 + /- 6.7 days for PEI group ( p = 0.01 ) . There was no difference in frequency of pneumonia or mortality between the two groups . CONCLUSION In severe head injury early tracheostomy decreases total days of mechanical ventilation or mechanical ventilation time after development of pneumonia To evaluate the attributable morbidity and mortality of ventilator-associated pneumonia ( VAP ) in intensive care unit ( ICU ) patients , we conducted a prospect i ve , matched cohort study . Patients expected to be ventilated for > 48 h were prospect ively followed for the development of VAP . To determine the excess ICU stay and mortality attributable to VAP , we matched patients with VAP to patients who did not develop clinical ly suspected pneumonia . We also conducted sensitivity analyses to examine the effect of different population s , onset of pneumonia , diagnostic criteria , causative organisms , and adequacy of empiric treatment on the outcome of VAP . One hundred and seventy-seven patients developed VAP . As compared with matched patients who did not develop VAP , patients with VAP stayed in the ICU for 4.3 d ( 95 % confidence interval [ CI ] : 1.5 to 7 . 0 d ) longer and had a trend toward an increase in risk of death ( absolute risk increase : 5.8 % ; 95 % CI : -2.4 to 14.0 d ; relative risk ( RR ) increase : 32.3 % ; 95 % CI : -20.6 to 85.1 % ) . The attributable ICU length of stay was longer for medical than for surgical patients ( 6 . 5 versus 0.7 d , p < 0.004 ) , and for patients infected with " high risk " organisms as compared with " low risk " organisms ( 9.1 d versus 2.9 d ) . The attributable mortality was higher for medical patients than for surgical patients ( RR increase of 65 % versus -27.3 % , p = 0 . 04 ) . Results were similar for three different VAP diagnostic criteria . We conclude that VAP prolongs ICU length of stay and may increase the risk of death in critically ill patients . The attributable risk of VAP appears to vary with patient population and infecting organism PURPOSE To compare the performance of an in-line heat moisture exchanging filter ( HMEF ) ( Pall BB-100 ; Pall Corporation ; East Hills , NY ) to a conventional heated wire humidifier ( H-wH ) ( Marquest Medical Products Inc. , Englewood , Colo ) in the mechanical ventilator circuit on the incidence of ventilator-associated pneumonia ( VAP ) and the rate of endotracheal tube occlusion . METHODS This report describes a prospect i ve , r and omized trial of 280 consecutive trauma patients in a 20-bed trauma ICU ( TICU ) . All intubated patients not ventilated elsewhere in the medical center prior to their TICU admission were r and omized to either an in-line HMEF or a H-wH in the breathing circuit . Ventilator circuits were changed routinely every 7 days , and closed system suction catheters were changed every 3 days . HMEFs were changed every 24 h , or more frequently if necessary . A specific endotracheal tube suction and lavage protocol was not employed . Patients were dropped from the HMEF group if the filter was changed more than three times a day or the patient was placed on a regimen of ultra high-frequency ventilation . The Centers for Disease Control and Prevention ( CDC ) criteria for diagnosis of pneumonia were used ; early-onset , community-acquired pneumonia was defined if CDC criteria were met in < or =3 days , and late-onset , hospital-acquired pneumonia was defined if criteria were met in > 3 days . Laboratory and chest radiograph interpretation were blinded . RESULTS The patient ages ranged from 15 to 95 years in the HMEF group and 16 to 87 years in the H-wH group ( p = not significant ) , with a mean age of 46 years and 48 years , respectively . The male to female ratio ranged between 78 to 82%/22 to 18 % , respectively , and 55 % of all admissions were related to blunt trauma , 40 % secondary to penetrating trauma , and 5 % to major burns . There was no difference in Injury Severity Score ( ISS ) between the two groups . Moreover , there was no significant difference in mean ISS among those who did not develop pneumonia and those patients who developed either early-onset , community-acquired or late-onset , hospital-acquired pneumonia . The HMEF nosocomial VAP rate was 6 % compared to 16 % for the H-wH group ( p<0.05 ) , and total ventilator circuit costs ( per group ) were reduced . There were no differences in duration of ventilation ( mean+/-SD ) if the patient did not develop pneumonia or if the patient developed an early-onset , community-acquired or a late-onset , hospital-acquired pneumonia . Moreover , total TICU days were reduced in the HMEF group . In addition , the incidence of partial endotracheal tube occlusion was not significantly different between the H-wH and the HMEF groups . CONCLUSIONS The HMEF used in this study reduced the incidence of late-onset , hospital-acquired VAP , but not early-onset , community-acquired VAP , compared to the conventional H-wH circuit . This was associated with a significant reduction in total ICU stay . Disposable ventilator circuit costs in the HMEF group were reduced compared to the H-wH group in whom circuit changes occurred at 7-day intervals . CLINICAL IMPLICATION S The use of the HMEF is a cost-effective clinical practice associated with fewer late-onset , hospital-acquired VAPs , and should result in improved re source allocation and utilization In 69 artificially ventilated patients the clinical , bacteriological and pharmacological effects of endotracheally administered tobramycin were studied in comparison to a control group . In the therapy group , 52 % of all specimens were sterile , in the control group only 25 % . During the first 4 days these changes were significant ( p < 0.05 ) . In the therapy group the endotracheal colonisation with ps . aeruginosa was significantly lower between the 4th and 14th day ( p < 0.05 ) . The incidence of secondary pneumonia was reduced from 42 % to 17.5 % ( not significant ) . Systemic administration of antibiotics , e.g. of aminoglycosides , was significantly more often necessary in the control group . No increasing of growth of fungi in the upper respiratory tract was observed , but these was a non-significantly higher incidence mainly of staph . epidermidis . The application of 80 mg tobramycin four times a day as an aerosol was well tolerated by the patients . Under there conditions , tobramycin could not be measured in the serum . No allergic reactions , increased respiratory pressures or bronchoconstrictions were observed In this prospect i ve , r and omized study , we evaluated whether a closed suctioning ( CS ) system ( TrachCare ) influences crossover contamination between bronchial system and gastric juices when compared with an open suctioning system ( OS ) . The secondary aims were an analysis of the frequency of ventilator-associated pneumonia ( VAP ) and an analysis of alteration in gas exchange . Antibiograms were performed from tracheal secretions and gastric juice aspirates on Days 1 and 3 of intubation in 24 patients in a medical intensive care unit . Five cross-contaminations were observed in the OS group on Day 3 versus Day 1 ; the 5 strains shared common genotypes as determined by r and om amplification of polymorphic DNA . No cross-contaminations were seen in the CS group ( P = 0.037 ) . VAP occurred in 5 patients of the OS group but in none of the CS group patients ( P = 0.037 ) . Spao(2 ) decreased significantly in the OS group compared with presuctioning values -- the opposite of the CS group . Whereas presuctioning values were comparable between groups , postsuctioning Spao(2 ) was significantly higher in the CS group . CS significantly reduced cross-contamination between bronchial system and gastric juices and reduced the incidence of VAP when compared with OS . Hypoxic phases can be reduced by the help of CS Objective : To improve patient safety by increasing heparin thromboprophylaxis for medical-surgical intensive care unit patients using a multiple- method approach to evidence -based guideline development and implementation . Design : Prospect i ve longitudinal observational study . Setting : Medical-surgical intensive care unit . Participants : Multidisciplinary clinicians caring for critically ill patients in a 15-bed medical-surgical closed intensive care unit . Interventions : Phase 1 was a 3-month baseline period during which we documented anticoagulation and mechanical thromboprophylaxis . Phase 2 was a 1-yr period in which we implemented a thromboprophylaxis guideline using a ) interactive multidisciplinary educational in-services ; b ) verbal reminders to the intensive care unit team ; c ) computerized daily nurse recording of thromboprophylaxis ; d ) weekly graphic feedback to individual intensivists on guideline adherence ; and e ) publicly displayed graphic feedback on group performance . Phase 3 was a 3-month follow-up period 10 months later , during which we documented thromboprophylaxis . Computerized daily nurse recording of thromboprophylaxis continued in this period . Measurements and Main Results : Intensive care unit and hospital mortality rates were similar across phases , although patients in phase 2 had higher Acute Physiology and Chronic Health Evaluation II scores than patients in phases 1 and 3 . The proportion ( median % [ interquartile range ] ) of intensive care unit patient-days of heparin thromboprophylaxis in phases 1 , 2 , and 3 was 60.0 ( 0 , 100 ) , 90.9 ( 50 , 100 ) , and 100.0 ( 60 , 100 ) , respectively ( p = .01 ) . The proportion ( median % [ interquartile range ] ) of days during which heparin thromboprophylaxis was omitted in error in phases 1 , 2 , and 3 was 20 ( 0 , 53.8 ) , 0 ( 0 , 6.3 ) , and 0 ( 0 , 0 ) , respectively ( p < .001 ) . Conclusions : After development and implementation of an evidence -based thromboprophylaxis guideline , we found significantly more patients receiving heparin thromboprophylaxis . Guideline adherence was maintained 1 yr later . Further research is needed on which are the most effective strategies to implement patient safety initiatives in the intensive care unit Objective To determine the effect of an institutional approach to the care of patients requiring mechanical ventilation for longer than three consecutive days in five adult intensive care units ( ICU ) on clinical and financial outcomes . Design A multidisciplinary team was selected from five adult ICUs to design the approach . Planning occurred from August 1999 to September 2000 . The process was called outcomes management ( OM ) and included an evidence -based clinical pathway , protocol s for weaning and sedation use , and the selection of four advanced practice nurses ( called outcomes managers ) to manage and monitor the program . Setting The project was completed in a 550-bed mid-Atlantic academic medical center . The ICUs included the following : coronary care , medical ICU , neuroscience ICU , surgical trauma ICU , and thoracic cardiovascular ICU . Patients The sample included 595 pre-OM patients and 510 post-OM patients mechanically ventilated for greater than three consecutive days . Interventions Full implementation of the OM approach occurred in March 2001 . Retrospective baseline ( 18 months pre-OM ) and prospect i ve ( 12 months OM ) clinical and financial data were compared . Measurements and Main Results Statistically significant differences in clinical outcomes were demonstrated in the managed patients compared with those managed before the institutional approach . Outcomes include ventilator duration ( median days declined from ten to nine ; p = .0001 ) , ICU length of stay ( median days declined from 15 to 12 ; p = .0008 ) , hospital length of stay ( median days declined from 22 to 20 ; p = .0001 ) , and mortality rate ( declined from 38 % to 31 % , p = .02 ) . More than $ 3,000,000 cost savings were realized in the OM group . Conclusions This institutional approach to the care of patients ventilated > 3 days improved all clinical and financial outcomes of interest . To date , few similar initiatives have demonstrated similar results . The approach and lessons learned in this process improvement project may be helpful to other institutions attempting to improve outcomes in this vulnerable population A prospect i ve , r and omized , controlled study was undertaken to compare the Pall Ultipor breathing circuit filter ( PUBCF ) , a heat- and -moisture exchanger , and heated hot water systems ( HHWSs ) in ICU patients su bmi tted to controlled mechanical ventilation . Humidification of inspired gas and bacterial contamination of breathing circuits were evaluated . During the study , there were six episodes of tracheostomy tube ( TT ) occlusion in six patients included in the PUBCF group . No patient out of 42 included in the HHWS group experienced this complication ( p less than 0.01 ) . There were 4 percent of days with thick and tenacious bronchial secretions in the PUBCF group and no case in the HHWS group ( p less than 0.02 ) . In the PUBCF group , 23 percent of days with hypothermia were noted as opposed to 12 percent in the HHWS group ( p less than 0.01 ) . Fewer breathing circuits were found to be contaminated in the PUBCF group ( 11 percent ) than in the HHWS group ( 54 percent , p less than 0.01 ) . In patients with an organism growing in bronchial specimens , the same organism was found to contaminate the breathing circuit in 10 percent of cases in the PUBCF group and 77 percent of cases in the HHWS ( p less than 0.01 ) . We conclude that , in the conditions of this study , the PUBCF did not provide sufficient humidification of inspired gas in ICU patients . Protection against contamination of breathing circuits was effective , but 10 percent of patients remained at risk for this complication RATIONALE AND OBJECTIVES The respective influence on the incidence of ventilator-associated pneumonia of currently available systems used for warming and humidifying the gases delivered to mechanically ventilated patients , that is , heated humidifiers and heat and moisture exchanger filters , remains controversial . METHODS We addressed this question in a multicenter r and omized study comparing heated humidifiers ( with heated circuits ) and filters in an unselected population of 369 intensive care patients receiving mechanical ventilation for more than 48 h. MAIN MEASUREMENTS AND RESULTS The diagnosis of pneumonia was confirmed according to strict microbiologic criteria . There was no difference in pneumonia rate between the two groups ( 53 of 184 [ 28.8 % ] versus 47 of 185 [ 25.4 % ] for humidifiers versus filters ; p = 0.48 ) , or in the incidence density of pneumonia ( 27.4/1,000 ventilatory days versus 25.3/1,000 ventilatory days for humidifiers versus filters ; p = 0.76 ) . The mean duration of mechanical ventilation did not differ between the two groups ( 14.9 + /- 15.1 versus 13.5 + /- 16.3 days for humidifiers versus filters , p = 0.36 ) . Endotracheal tube occlusion occurred , respectively , in five patients and one patient in the humidifier and filter groups ( p = 0.12 ) . Intensive care mortality was identical in the two groups ( about 33 % ) . CONCLUSION These results suggest that both heated humidifiers and heat and moisture exchanger filters can be used with no significant impact on the incidence of ventilator-associated pneumonia and that other criteria may justify their choice Context : Reducing aspiration of gastric contents by placing mechanically ventilated patients in a semirecumbent position has been associated with lower incidences of ventilator-associated pneumonia ( VAP ) . The feasibility and efficacy of this intervention in a larger patient population , however , are unknown . Objective : Assessment of the feasibility of the semirecumbent position for intensive care unit patients and its influence on development of VAP . Design : In a prospect i ve multicentered trial , critically ill patients undergoing mechanical ventilation were r and omly assigned to the semirecumbent position , with a target backrest elevation of 45 ° , or st and ard care ( i.e. , supine position ) with a backrest elevation of 10 ° . Main Outcome Measures : Backrest elevation was measured continuously during the first week of ventilation with a monitor-linked device . A deviation of position was defined as a change of the r and omized position > 5 ° . Diagnosis of VAP was made by quantitative cultures of sample s obtained by bronchoscopic techniques . Results : One hundred nine patients were assigned to the supine group and 112 to the semirecumbent group . Baseline characteristics were comparable for both groups . Average elevations were 9.8 ° and 16.1 ° at day 1 and day 7 , respectively , for the supine group and 28.1 ° and 22.6 ° at day 1 and day 7 , respectively , for the semirecumbent group ( p < .001 ) . The target semirecumbent position of 45 ° was not achieved for 85 % of the study time , and these patients more frequently changed position than supine-positioned patients . VAP was diagnosed in eight patients ( 6.5 % ) in the supine group and in 13 ( 10.7 % ) in the semirecumbent group ( NS ) , after a mean of 6 ( range , 3–9 ) and 7 ( range , 3–12 ) days , respectively . There were no differences in numbers of patients undergoing enteral feeding , receiving stress ulcer prophylaxis , or developing pressure sores or in mortality rates or duration of ventilation and intensive care unit stay between the groups . Conclusions : The targeted backrest elevation of 45 ° for semirecumbent positioning was not reached in the conditions of the present r and omized study . The achieved difference in treatment position ( 28 ° vs. 10 ° ) did not prevent the development of VAP In comatose patients admitted to an ICU , particularly those with head injury , the incidence of early onset pneumonia is exceedingly high . We performed an open , prospect i ve , r and omized , and controlled clinical trial aim ing at the reduction of the incidence of ventilator-associated pneumonia in head-injured patients and patients with stroke requiring mechanical ventilation . One hundred patients were included because of head injury or coma caused by medical stroke and with Glasgow coma scores < or = 12 and mechanical ventilation > 72 h. Patients eligible for the study ( n = 50 ) received cefuroxime intravenously ( two 1,500-mg doses 12 h apart after intubation ) ( the cefuroxime group ) and 50 patients not receiving cefuroxime formed the control group . In the former group patients did not receive any other antibiotics before the end-point determination , whereas in the latter , 17 patients received prophylactic antibiotics as prescribed by the attending physician . The global incidence of microbiologically confirmed pneumonia was 37 % ( n = 37 ) ; 12 ( 24 % ) belonged to the cefuroxime group , and 25 ( 50 % ) belonged to the control group ( p = 0.007 ) . Early-onset pneumonia accounted for 70 % of all the pneumonia episodes ( n = 26 ) , eight ( 67 % ) belonging to the cefuroxime group , and 18 ( 72 % ) belonging to the control group ( p = 0.02 ) . In the control group , four of 17 ( 23 % ) patients receiving prior antibiotics developed pneumonia , whereas 21 of 33 ( 64 % ) patients who did not receive antibiotics developed pneumonia ( p = 0.016 ) . The multivariate analysis revealed that the duration of mechanical ventilation ( per each day ) was an independent risk factor significantly associated to the development of pneumonia . Furthermore , the use of cefuroxime and /or prior antibiotics in the control group , before the pneumonia episode , had a protective effect against its development . No differences were found with regard to mortality and morbidity when comparing the study population with the control group . Nevertheless , when comparing patients with pneumonia ( from both study and control groups ) with those without it , there was a decrease in total hospital stay ( 35 + /- 13 versus 25 + /- 14 d , p = 0.048 ) and ICU stay ( 20 + /- 11 versus 11 + /- 7 d , p = 0.001 ) . The study demonstrated that the administration of two single high doses 1,500 mg each of cefuroxime after the intubation of patients comatose because of head injury or medical stroke is an effective prophylactic strategy to decrease the incidence of ventilator-associated pneumonia STUDY OBJECTIVES To determine whether the application of continuous aspiration of subglottic secretions ( CASS ) is associated with a decreased incidence of ventilator-associated pneumonia ( VAP ) . DESIGN Prospect i ve clinical trial . SETTING Cardiothoracic ICU ( CTICU ) of Barnes-Jewish Hospital , St. Louis , a university-affiliated teaching hospital . PATIENTS Three hundred forty-three patients undergoing cardiac surgery and requiring mechanical ventilation in the CTICU . INTERVENTIONS Patients were assigned to receive either CASS , using a specially design ed endotracheal tube ( Hi-Lo Evac ; Mallinckrodt Inc ; Athlone , Irel and ) , or routine postoperative medical care without CASS . RESULTS One hundred sixty patients were assigned to receive CASS , and 183 were assigned to receive routine postoperative medical care without CASS . The two groups were similar at the time of r and omization with regard to demographic characteristics , surgical procedures performed , and severity of illness . Risk factors for the development of VAP were also similar during the study period for both treatment groups . VAP was seen in 8 patients ( 5.0 % ) receiving CASS and in 15 patients ( 8 . 2 % ) receiving routine postoperative medical care without CASS ( relative risk , 0.61 % ; 95 % confidence interval , 0.27 to 1.40 ; p = 0 . 238 ) . Episodes of VAP occurred statistically later among patients receiving CASS ( [ mean + /- SD ] 5.6 + /- 2.3 days ) than among patients who did not receive CASS ( 2.9 + /- 1.2 days ) ; ( p = 0.006 ) . No statistically significant differences for hospital mortality , overall duration of mechanical ventilation , lengths of stay in the hospital or CTICU , or acquired organ system derangements were found between the two treatment groups . No complications related to CASS were observed in the intervention group . CONCLUSIONS Our findings suggest that CASS can be safely administered to patients undergoing cardiac surgery . The occurrence of VAP can be significantly delayed among patients undergoing cardiac surgery using this simple-to-apply technique OBJECTIVE This study was conducted to develop evidence -based clinical practice guidelines for nutrition support ( ie , enteral and parenteral nutrition ) in mechanically ventilated critically ill adults . OPTIONS The following interventions were systematic ally review ed for inclusion in the guidelines : enteral nutrition ( EN ) versus parenteral nutrition ( PN ) , early versus late EN , dose of EN , composition of EN ( protein , carbohydrates , lipids , immune-enhancing additives ) , strategies to optimize delivery of EN and minimize risks ( ie , rate of advancement , checking residuals , use of bedside algorithms , motility agents , small bowel versus gastric feedings , elevation of the head of the bed , closed delivery systems , probiotics , bolus administration ) , enteral nutrition in combination with supplemental PN , use of PN versus st and ard care in patients with an intact gastrointestinal tract , dose of PN and composition of PN ( protein , carbohydrates , IV lipids , additives , vitamins , trace elements , immune enhancing substances ) , and the use of intensive insulin therapy . OUTCOMES The outcomes considered were mortality ( intensive care unit [ ICU ] , hospital , and long-term ) , length of stay ( ICU and hospital ) , quality of life , and specific complications . EVIDENCE We systematic ally search ed MEDLINE and CINAHL ( cumulative index to nursing and allied health ) , EMBASE , and the Cochrane Library for r and omized controlled trials and meta-analyses of r and omized controlled trials that evaluated any form of nutrition support in critically ill adults . We also search ed reference lists and personal files , considering all articles published or unpublished available by August 2002 . Each included study was critically appraised in duplicate using a st and ard scoring system . VALUES For each intervention , we considered the validity of the r and omized trials or meta-analyses , the effect size and its associated confidence intervals , the homogeneity of trial results , safety , feasibility , and the economic consequences . The context for discussion was mechanically ventilated patients in Canadian ICUs . BENEFITS , HARMS , AND COSTS The major potential benefit from implementing these guidelines is improved clinical outcomes of critically ill patients ( reduced mortality and ICU stay ) . Potential harms of implementing these guidelines include increased complications and costs related to the suggested interventions . SUMMARIES OF EVIDENCE AND RECOMMENDATIONS : When considering nutrition support in critically ill patients , we strongly recommend that EN be used in preference to PN . We recommend the use of a st and ard , polymeric enteral formula that is initiated within 24 to 48 hours after admission to ICU , that patients be cared for in the semirecumbent position , and that arginine-containing enteral products not be used . Strategies to optimize delivery of EN ( starting at the target rate , use of a feeding protocol using a higher threshold of gastric residuals volumes , use of motility agents , and use of small bowel feeding ) and minimize the risks of EN ( elevation of the head of the bed ) should be considered . Use of products with fish oils , borage oils , and antioxidants should be considered for patients with acute respiratory distress syndrome . A glutamine-enriched formula should be considered for patients with severe burns and trauma . When initiating EN , we strongly recommend that PN not be used in combination with EN . When PN is used , we recommend that it be supplemented with glutamine , where available . Strategies that maximize the benefit and minimize the risks of PN ( hypocaloric dose , withholding lipids , and the use of intensive insulin therapy to achieve tight glycemic control ) should be considered . There are insufficient data to generate recommendations in the following areas : use of indirect calorimetry ; optimal pH of EN ; supplementation with trace elements , antioxidants , or fiber ; optimal mix of fats and carbohydrates ; use of closed feeding systems ; continuous versus bolus feedings ; use of probiotics ; type of lipids ; and mode of lipid delivery . VALIDATION This guideline was peer- review ed and endorsed by official representatives of the Canadian Critical Care Society , Canadian Critical Care Trials Group , Dietitians of Canada , Canadian Association of Critical Care Nurses , and the Canadian Society for Clinical Nutrition . SPONSORS This guideline is a joint venture of the Canadian Critical Care Society , the Canadian Critical Trials Group , the Canadian Society for Clinical Nutrition , and Dietitians of Canada . The Canadian Critical Care Society and the Institute of Nutrition , Metabolism , and Diabetes of the Canadian Institutes of Health Research provided funding for development of this guideline Objective : To compare the incidence of ventilator-associated pneumonia ( VAP ) in patients ventilated in intensive care by means of circuits humidified with a hygroscopic heat- and -moisture exchanger with a bacterial viral filter ( HME ) or hot-water humidification with a heater wire in both inspiratory and expiratory circuit limbs ( DHW ) or the inspiratory limb only ( SHW ) . Design : A prospect i ve , r and omized trial . Setting : A metropolitan teaching hospital 's general intensive care unit . Patients : Three hundred eighty-one patients requiring a minimum period of mechanical ventilation of 48 hrs . Interventions : Patients were r and omized to humidification with use of an HME ( n = 190 ) , SHW ( n = 94 ) , or DHW ( n = 97 ) . Measurements and Main Results : Study end points were VAP diagnosed on the basis of Clinical Pulmonary Infection Score ( CPIS ) ( 1 ) , HME resistance after 24 hrs of use , endotracheal tube resistance , and HME use per patient . VAP occurred with similar frequency in all groups ( 13 % , HME ; 14 % , DHW ; 10 % , SHW ; p = 0.61 ) and was predicted only by current smoking ( adjusted odds ratio [ AOR ] , 2.1 ; 95 % confidence interval [ CI ] , 1.1–3.9 ; p = .03 ) and ventilation days ( AOR , 1.05 ; 95 % CI , 1.0–1.2 ; p = .001 ) ; VAP was less likely for patients with an admission diagnosis of pneumonia ( AOR , 0.40 ; 95 % CI , 0.4–0.2 ; p = .04 ) . HME resistance after 24 hrs of use measured at a gas flow of 50 L/min was 0.9 cm H2O ( 0.4–2.9 ) . Endotracheal tube resistance was similar for all three groups ( 16–19 cm H2O min/L ; p = .2 ) , as were suction frequency , secretion thickness , and blood on suctioning ( p = .32 , p = .06 , and p = .34 , respectively ) . The HME use per patient per day was 1.13 . Conclusions : Humidification technique does not influence either VAP incidence or secretion characteristics , but HMEs may have air-flow resistance higher than manufacturer specifications after 24 hrs of use Objective : The aim of this study was to analyze the prevalence of ventilator-associated pneumonia ( VAP ) using a closed-tracheal suction system vs. an open system . Design : Prospect i ve and r and omized study , from October 1 , 2002 , to December 31 , 2003 . Setting : A 24-bed medical-surgical intensive care unit in a 650-bed tertiary hospital . Patients : Patients requiring mechanical ventilation for > 24 hrs . Interventions : Patients were r and omized into two groups ; one group was suctioned with the closed-tracheal suctioning system and another group with the open system . Measurements : Throat swabs were taken at admission and twice a week until discharge to classify pneumonia in endogenous and exogenous . Main Results : A total of 443 patients ( 210 with closed-tracheal suction system and 233 with the open system ) were included . There were no significant differences between groups of patients in age , sex , diagnosis groups , mortality , number of aspirations per day , and Acute Physiology and Chronic Health Evaluation II score . No significant differences were found in either the percentage of patients who developed VAP ( 20.47 % vs. 18.02 % ) or in the number of VAP cases per 1000 mechanical ventilation-days ( 17.59 vs. 15.84 ) . There were also no differences in the VAP incidence by mechanical ventilation duration . At the same time , we did not find any differences in the incidence of exogenous VAP . Likewise , there were also no differences in the microorganisms responsible for pneumonia . Patient cost per day for the closed suction was more expensive than the open suction system ( $ 11.11 ± $ 2.25 vs. $ 2.50 ± $ 1.12 , p < .001 ) . Conclusion : We conclude that in our study , the closed-tracheal suction system did not reduce VAP incidence , even for exogenous pneumonia Chronic microaspiration through a tracheal cuff is the main culprit in the penetration and colonization of the lower respiratory tract . A total of 145 patients intubated for more than 3 days were r and omly assigned to a double nosocomial pneumonia ( NP ) prevention : 1-Prevention of aspiration by hourly subglottic secretion drainage ( SSD ) with a specific endotracheal tube ( HI-LO Evac tube , Mallinckrodt ) ; 2-Prevention of gastric colonization using either sucralfate or antacids . Four r and om groups were defined , similar in age and severity of illness . Subglottic secretion drainage treatment was associated with : a ) a twice lower incidence of NP ( no-SSD : 29.1 % , SSD : 13 % ) ; b ) a prolonged time of onset of NP ( no-SSD : 8.3±5 days , SSD : 16.2±11 days ) ; c ) a decrease in the colonization rate from admission to end-point day in tracheal aspirates ( no-SSD:+21.3 % , SSD:+6.6 % ) and in subglottic secretions ( no-SSD:+33.4 % , SSD:+2.1 % ) . Sucralfate was not associated with a significantly lower incidence of NP ( antacids : 23.6 % , sucralfate : 17.8 % ) , but with a lower increase in the colonization rate in subglottic and gastric aspirates , from admission to end-point day STUDY OBJECTIVE To evaluate the safety of a combined heat and moisture exchanger filter ( HMEF ) for the conditioning of inspired gas in long-term mechanical ventilation ( MV ) . DESIGN R and omized controlled trial . SETTING Medical ICU in a large teaching hospital . PATIENTS One hundred fifteen consecutive patients who required > or = 48 h of MV . INTERVENTIONS Patients were r and omized at intubation time ( day 1 ) to receive inspired gas conditioned either by a water-bath humidifier heated at 32 degrees C ( HWBH ) or by an HMEF ( Hygroster ; DAR ; Mir and ola , Italy ) . MEASUREMENTS AND MAIN RESULTS The two study groups were comparable in terms of primary pathologic condition at the time of hospital admission , disease severity as measured by the Simplified Acute Physiology Score , and ICU mortality . They did not differ with respect to ventilator days per patient ( mean + /- SD : HMEF , 7.6 + /- 6.5 ; HWBH , 7.8 + /- 5.8 ) , incidence of endotracheal tube obstruction ( HMEF , 0/59 ; HWBH , 1/56 ) , and incidence of hypothermic episodes ( HMEF , five ; HWBH , two ) . In 41 patients receiving MV for > or = 5 days , the morphologic integrity of respiratory epithelium was evaluated on day 1 and day 5 , using a cytologic examination of tracheal aspirate smears . The state of ciliated epithelium was scored on a scale from 0 ( poorest integrity ) to 1,200 ( maximum integrity ) , according to a well-described method . In both patient groups , the scores slightly but significantly decreased from day 1 to day 5 ( mean + /- SD : HWBH , from 787 + /- 104 to 745 + /- 88 ; HMEF , from 813 + /- 79 to 739 + /- 62 ; p < 0.01 for both groups ) ; there were no statistically significant differences between groups . CONCLUSIONS These data indicate acceptable safety of HMEFs of the type used in the present study for long-term mechanical ventilation The contribution of ventilator circuit bacterial contamination to the occurrence of ventilator-associated pneumonia remains controversial . In a previous study , we found that the incidence of pneumonia was identical with ventilator circuit changes every 48 h and with no ventilator circuit changes . The present study prospect ively assessed whether keeping ventilator circuits clean with a heat and moisture exchanger exhibiting antimicrobial barrier properties affects patient colonization and the incidence of nosocomial pneumonia in patients receiving mechanical ventilation for more than 48 h. Consecutive patients were r and omly allocated to humidification with either a heat and moisture exchanger ( Group 1 , n = 61 ) or a heated humidifier ( Group 2 , n = 70 ) . In both groups , no circuit changes were performed throughout ventilatory support . Duration of mechanical ventilation was identical in both groups ( 10 + /- 8.6 d ( range : 2 to 47 ) in Group 1 and 12.5 + /- 14.2 d [ range : 2 to 85 ] in Group 2 ) . The incidence of pneumonia ( positive quantitative culture of protected brush specimen ) was similar in both groups ( 6/61 and 8/70 in Groups 1 and 2 , respectively ; p = 0.8 ) , as was duration of ventilation prior to pneumonia ( 9 + /- 5.9 versus 8.2 + /- 5.7 d ; p = 0.8 ) . Ventilator tubing contamination was considerably reduced with the use of a heat and moisture exchanger . In contrast , bacterial colonization of the pharynx and trachea was identical in both groups . These results suggest that circuit colonization plays little or no role in the occurrence of ventilator-associated pneumonia , provided usual maintenance pre caution s are applied . ( ABSTRACT TRUNCATED AT 250 WORDS Objective To examine the physiologic consequences and costs associated with two methods of endotracheal suctioning : closed vs. open . Design A prospect i ve , r and omized , controlled study . Setting An eight-bed trauma intensive care unit ( ICU ) in a 460-bed level I trauma center . Patients The study included 35 trauma/general surgery patients ( 16 in the open suction group , 19 in the closed suction group ) who were treated with a total of 276 suctioning procedures ( 127 open , 149 closed ) . Measurements and Main Results Physiologic data collected after hyperoxygenation , immediately after suctioning , and 30 sees after suctioning , were compared with baseline values . Open endotracheal suctioning result ed in significant increases in mean arterial pressure throughout the suctioning procedure . Both methods result ed in increased mean heart rates . However , 30 sees after the procedure , the open-suction method was associated with a significantly higher mean heart rate than was the closed method . Closed suctioning was associated with significantly fewer dysrhythmias . Arterial oxygen saturation and systemic venous oxygen saturation decreased with open suctioning . In contrast , arterial oxygen saturation and systemic venous oxygen saturation increased with the closed suction method . There was no difference between the two methods in the occurrence of nosocomial pneumonia . Open endotracheal suctioning cost 1.88 more per patient per day and required more nursing time . Conclusions The closed suction method result ed in significantly fewer physiologic disturbances . Closed suctioning appears to be an effective and cost-efficient method of endotracheal suctioning that is associated with fewer suction-induced complications . ( Crit Care Med 1994 ; 22:658–666 Objective : To evaluate the effect of a regular oropharyngeal application of povidone-iodine on the prevalence of ventilator-associated pneumonia in patients with severe head trauma . Design : Prospect i ve r and omized study . Setting : A surgical intensive care unit of a university hospital . Interventions : Patients with severe head trauma ( Glasgow Coma Score of ≤8 ) expected to need ventilation for ≥2 days were prospect ively r and omized into three groups : those receiving nasopharynx and oropharynx rinsing with 20 mL of a 10 % povidone-iodine aqueous solution , reconstituted in a 60-mL solution with sterile water ( povidone-iodine group ) ; those receiving nasopharynx and oropharynx rinsing with 60 mL of saline solution ( saline group ) ; or those undergoing a st and ard regimen without any instillation but with aspiration of oropharyngeal secretions ( control group ) . Measurements and Main Results : The prevalence of ventilator-associated pneumonia was compared among the three groups . A total of 98 patients were analyzed ( povidone-iodine group , n = 36 ; saline group , n = 31 ; and control group , n = 31 ) . A total of 28 cases of ventilator-associated pneumonia were diagnosed . There was a significant decrease in the rate of ventilator-associated pneumonia in the povidone-iodine group when compared with the saline and control groups ( 3 of 36 patients [ 8 % ] vs. 12 of 31 patients [ 39 % ] and 13 of 31 patients [ 42 % ] , respectively ; p = .003 and .001 , respectively ) . The length of stay and mortality in the surgical intensive care unit were not statistically different between the three groups . Conclusions : The regular administration of povidone-iodine may be an effective strategy for decreasing the prevalence of ventilator-associated pneumonia in patients with severe head trauma The purpose of this study was to determine the safety and cost-effectiveness of not routinely changing in-line suction catheters for patients requiring mechanical ventilation . Patients were r and omly assigned to receive either no routine in-line suction catheter changes ( n = 258 ) or in-line suction catheter changes every 24 h ( n = 263 ) . The main outcome measure was the incidence of ventilator-associated pneumonia . Other outcomes evaluated included hospital mortality , acquired organ system derangements , duration of mechanical ventilation , lengths of intensive care and hospital stay , and the cost for in-line suction catheters . Ventilator-associated pneumonia was seen in 38 patients ( 14.7 % ) receiving no routine in-line suction catheter changes and in 39 patients ( 14.8 % ) receiving in-line suction catheter changes every 24 h ( relative risk , 0.99 ; 95 % CI , 0.66 to 1.50 ) . No statistically significant differences for hospital mortality , lengths of stay , the number of acquired organ system derangements , death in patients with ventilator-associated pneumonia , or mortality directly attributed to ventilator-associated pneumonia were found between the two treatment groups . Patients receiving in-line suction catheter changes every 24 h had 1,224 catheter changes costing a total of $ 11,016 ; patients receiving no routine in-line suction catheter changes had a total of 93 catheter changes costing $ 837 . Our findings suggest that the elimination of routine in-line suction catheter changes is safe and can reduce the costs associated with providing mechanical ventilation The risk of nosocomial pneumonia and atelectasis is high among critically ill immobilized patients . We hypothesized that continuous turning on the kinetic treatment table would reduce their incidence . Sixty-five critically ill patients , immobilized because of head injury or traction , were prospect ively r and omized for treatment in a conventional bed ( n = 38 ) or the kinetic treatment table ( n = 27 ) . Patients were well matched for baseline demographic and pulmonary risk factors . Patients in the conventional bed group had a higher incidence of cigarette smoking . The combined incidence of significant atelectasis or pneumonia was higher ( 66 % ) in the conventional vs. kinetic treatment table ( 33 % ) groups ( p less than .01 ) . Atelectasis , pneumonia , adult respiratory distress syndrome , requirements for ventilator treatment , for PEEP , and for an FIO2 greater than 0.50 were not significantly different , but tended to be higher in the control group . Survival and the incidence of decubitus ulcers were similar We tested the hypothesis that the incidence of LRTI in critically ill blunt trauma victims can be reduced by employing continuous postural oscillation . Within 24 h of admission to the SICU , 106 patients were prospect ively r and omized to either a conventional bed or a RRKTT . Seven patients who were discharged from the SICU in less than 24 h were excluded from the data analyses . Until discharge from the SICU , patients were monitored daily for development of LRTI or pneumonia . Among 48 patients in the control group , 28 met criteria for LRTI and 19 met criteria for pneumonia . Among 51 patients in the RRKTT group , 13 developed LRTI and 7 developed pneumonia . The differences between groups for all LRTI and pneumonia were both significant . We conclude that continuous postural oscillation decreases the risk of pulmonary sepsis in victims of major blunt trauma |
12,420 | 17,233,912 | Test-retest reliability was demonstrated for the FAOS , the FADI and the FAAM but not for the AJFAT .
For none of the studied instruments , the internal consistency was sufficiently demonstrated .
The presence of floor- and ceiling effects was assessed for the FAOS but ceiling effects were present for all subscales .
Responsiveness was demonstrated for the AJFAT , FADI and the FAAM .
Only for the FAAM , a minimal clinical important difference ( MCID ) was presented .
Conclusion The FADI and the FAAM can be considered as the most appropriate , patient-assessed tools to quantify functional disabilities in patients with chronic ankle instability . | Background The assessment of outcomes from the patient 's perspective becomes more recognized in health care .
Also in patients with chronic ankle instability , the degree of present impairments , disabilities and participation problems should be documented from the perspective of the patient .
The decision about which patient-assessed instrument is most appropriate for clinical practice should be based upon systematic review s. Only rating scales constructed for patients with acute ligament injuries were systematic ally review ed in the past .
The aim of this study was to review systematic ally the clinimetric qualities of patient-assessed instruments design ed for patients with chronic ankle instability . | Functional outcome , stability at radiographic investigation and ankle joint torque after anatomical reconstruction of the lateral ankle ligaments were evaluated in patients with early postoperative mobilization versus those with cast immobilization . Thirty patients with chronic lateral ligament instability of the ankle underwent anatomical reconstruction of the ligaments . Postoperatively the patients were r and omly allocated to two groups : Group A ( n=15 ) were immobilized in a below-knee plaster for 6 weeks and Group B ( n=15 ) underwent early controlled range of motion training using an Air-Cast ankle brace . The functional results were evaluated using a scoring scale and objective results using st and ardized stress radiographs . Also eccentric and concentric muscle torque at 60 degrees/s was measured in plantar flexion and dorsiflexion , respectively . The functional results were satisfactory in 12/15 ankles in Group A and 14/15 in Group B ( n.s . ) . All the patients with satisfactory results regained normal range of motion . Patients with unsatisfactory results had either residual pain or recurrent instability . In Group B , the strength measurements revealed significantly higher peak torque values after three months in plantar flexion at 60 degrees/s . Six months postoperatively , the torque values did not differ significantly between the groups . Also , there was no group difference in the laxity of the ankle joint , including both anterior talar translation test and talar tilt test , at the two-year follow-up . One patient had a superficial wound infection . We conclude that after the reconstruction of chronic lateral ligament instability of the ankle the functional and stability results were equally good with early postoperative mobilization and 6-week immobilization . However , using early mobilization plantar flexion strength was regained earlier than with cast immobilization , without any risk of short- or medium-term complications , such as increased ankle laxity . We recommend early mobilization after anatomical reconstruction of the lateral ankle ligaments Sixty consecutive collegiate athletes with “ high ” ankle symptoms were prospect ively evaluated over a 3-year period in an effort to better define this debilitating ankle injury . All athletes included in this study had tenderness over the distal anterior tibiofibular ligament , tenderness proximally along the interosseous membrane , and functional disability . No study subject had a fracture or frank tibia-fibula diastasis . The severity of the sprain was quantified using the interosseous “ tenderness length . ” A st and ard rehabilitation protocol was followed by all patients . Athletes returned to competition when they could perform all functional testing without difficulty . Time to return to full competitive activity averaged 13.4 days . The number of days missed from competition was statistically related to the interosseous tenderness length ( P 0.0001 ) and to positive results on the squeeze test ( P 0.03 ) . Fifty-three of the 60 injured athletes were evaluated at least 6 months after injury . Patients rated their outcomes as good or excellent . Six of the patients experienced occasional ankle pain and stiffness , four patients reported recurrent ankle sprains , and one patient had heterotopic ossification formation STUDY DESIGN A nonr and omized 2-group pretest-posttest design . OBJECTIVES To determine the effects of a 4-week balance training program during stance on a single leg . BACKGROUND Individuals who have experienced multiple episodes of inversion ankle sprains often participate in balance training programs . Balance training is performed to treat existing proprioceptive deficits and to restore ankle joint stability , presumably by retraining altered afferent neuromuscular pathways . The effectiveness of such programs on individuals with functionally unstable ankles has yet to be established . METHODS AND MEASURES Prior to and following training , subjects with self-reported functionally unstable ankles ( 5 women and 8 men , mean age = 21.9 + /- 3.1 years ) and nonimpaired subjects ( 6 women and 7 men , mean age = 21.2 + /- 2.5 years ) completed a static balance assessment for both limbs as well as the ankle joint functional assessment tool question naire ( AJFAT ) . The subjects from both groups participated in a unilateral , multilevel , static and dynamic balance training program 3 times a week for 4 weeks . Subjects from the experimental group trained only the involved limb , and the nonimpaired group trained a r and omly selected limb . A stability index ( SI ) was calculated during the balance assessment to indicate the amount of platform motion . Compared to low stability indices , high stability indices indicate greater platform motion during stance and therefore less stability . RESULTS Following training , subjects from both groups demonstrated significant improvements in balance ability . When balance was assessed at a low resistance to platform tilt ( stability level 2 ) , the posttraining scores of both the subjects with unstable ankles ( mean SI = 2.63 + /- 1.92 ) and the nonimpaired subjects ( mean SI = 2.69 + /- 2.32 ) were significantly better than their pretraining scores ( mean SIs = 5.93 + /- 3.65 and 4.67 + /- 3.43 , respectively ) . Assessed at a high resistance to platform tilt ( stability level 6 ) , the posttraining scores of both subjects with unstable ankles ( mean SI = 1.27 + /- 0.66 ) and the nonimpaired subjects ( mean SI = 1.37 + /- 0.66 ) were significantly better than their pretraining scores ( mean SIs = 2.30 + /- 1.88 and 2.04 + /- 1.43 , respectively ) . Additionally , the posttraining AJFAT scores of subjects with unstable ankles ( 25.78 + /- 3.80 ) and the nonimpaired subjects ( 29.15 + /- 5.27 ) were significantly greater than their pretraining scores ( 17.11 + /- 3.44 and 22.92 + /- 5.22 , respectively ) , indicating an overall improvement in perceived ankle joint functional stability . CONCLUSIONS This study suggests that balance training is an effective means of improving joint proprioception and single-leg st and ing ability in subjects with unstable and nonimpaired ankles A bi-directional bicycle pedal that combines proprioceptive training and evertor strengthening has been developed for the treatment of residual instability after ankle sprains . A prospect i ve r and omized study was carried out on 19 subjects with recurrent ankle sprains and positive stress X-ray films . The subjects were r and omized to use either a bi-directional test pedal or a traditional uni-directional bicycle pedal and then completed a 6-week high-intensity training program on a cycle ergometer . Assessment of training intensity level was based on maximum oxygen uptake values , heart rate and lactate concentration in blood at various submaximal workloads . After completion of the training program , the subjects who had used the test pedal increased peak eversion torque at 180 degrees degrees s-1 by 14.2 % ( P = 0.020 ) , reduced figure-of-eight running time by 0.24 s ( P = 0.003 ) , improved single leg stance speed from 72.5 % to the maximum speed of 80 % ( P = 0.005 ) , and improved Karlsson functional score by 5.1 points ( P = 0.005 ) . In the control group , single leg stance improved from 56.1 to 67.8 % ( P = 0.018 ) , but otherwise no significant effects were found . This study indicates that short-term high-intensity training with a bi-directional pedal improves ankle performance and may be an option in the treatment of recurrent ankle sprains Objectives : To examine the effect of six weeks of strength and proprioception training on eversion to inversion isokinetic strength ratios ( E/I ratios ) in subjects with unilateral functional ankle instability . Methods : Thirty eight subjects were r and omly assigned to one of four treatment groups : strength training ( S ) ; proprioception training ( P ) ; strength + proprioception training ( B ) ; control ( C ) . Isokinetic strength was tested before and after training using a Kin Com 125 automatic positioning isokinetic dynamometer . Subtalar joint eversion and inversion motions were tested both concentrically and eccentrically through a range of motion involving 40 ° . All peak torque and average torque values were normalised for body mass . E/I ratios were calculated from average torque and peak torque measures by taking the concentric eversion value and combining it with the eccentric inversion value . Data were analysed using a mixed model analysis of variance with repeated measures on the test factor . Average torque and peak torque E/I ratios at 30 and 120 ° /s were analysed separately . Results : There were no significant differences in average torque and peak torque E/I ratios of the functionally unstable ankle for any of the groups after training compared with before . Conclusions : Six weeks of strength and proprioception training ( either alone or combined ) had no effect on isokinetic measures of strength in subjects with self reported unilateral functional instability . Further studies examining this agonist ( concentric ) to antagonist ( eccentric ) muscle group strength ratio are needed The purpose of this study was to examine a young athletic population to up date the data regarding epidemiology and disability associated with ankle injuries . At the United States Military Academy , all cadets presenting with ankle injuries during a 2-month period were included in this prospect i ve observational study . The initial evaluation included an extensive question naire , physical examination , and radiographs . Ankle sprain treatment included a supervised rehabilitation program . Subjects were reevaluated at 6 weeks and 6 months with subjective assessment , physical examination , and functional testing . The mean age for all subjects was 20 years ( range , 17–24 years ) . There were 104 ankle injuries accounting for 23 % of all injuries seen . There were 96 sprains , 7 fractures , and 1 contusion . Of the 96 sprains , 4 were predominately medial injuries , 76 were lateral , and 16 were syndesmosis sprains . Ninety-five percent had returned to sports activities by 6 weeks ; however , 55 % of these subjects reported loss of function or presence of intermittent pain , and 23 % had a decrement of > 20 % in the lateral hop test when compared with the uninjured side . At 6 months , all subjects had returned to full activity ; however , 40 % reported residual symptoms and 2.5 % had a decrement of > 20 % on the lateral hop test . Neither previous injury nor ligament laxity was predictive of chronic symptomatology . Furthermore , chronic dysfunction could not be predicted by the grade of sprain ( grade I vs. II ) . The factor most predictive of residual symptoms was a syndesmosis sprain , regardless of grade . Syndesmosis sprains were most prevalent in collision sports . This study demonstrates that even though our knowledge and underst and ing of ankle sprains and rehabilitation of these injuries have progressed in the last 20 years , chronic ankle dysfunction continues to be a prevalent problem . The early return to sports occurs after almost every ankle sprain ; however , dysfunction persists in 40 % of patients for as long as 6 months after injury . Syndesmosis sprains are more common than previously thought , and this confirms that syndesmosis sprains are associated with prolonged disability Exercises to improve joint proprioception and coordination of the functionally unstable ankle are advocated throughout the literature , yet there is little evidence that these exercise have any effect on proprioception and balance . The purpose of this study was to determine the effects of a 6-week coordination and balance training program on proprioception of subjects with functional ankle instability . Forty-five subjects ( age = 22.53 + /- 3.95 years , height = 172.04 + /- 10.0 cm , weight = 71.72 + /- 15.7 kg ) were r and omly placed into a control ( Group 1 ) , sham ( Group 2 ) , or experimental ( Group 3 ) group . The experimental group trained 3 days per week , 10 minutes each day , performing various balance and proprioception exercises . Postural sway and active and passive joint position sense were assessed . Analysis of variance for postural sway modified equilibrium score for anterior and posterior sway , as well as medial and lateral sway revealed significant four-way interactions . Tukey post hoc analyses revealed that Group 3 performed significantly better ( p < .05 ) than Group 1 and Group 2 on the posttests . There were no significant differences for joint position sense or postural sway index . Results suggest that balance and coordination training can improve some measures of postural sway . It is still unclear if joint position sense can be improved in the functionally unstable ankle OBJECTIVE To examine the effects of ankle-strengthening exercises on joint position sense and strength development in subjects with functionally unstable ankles . DESIGN AND SETTING Subjects were r and omly assigned to a training or control group . The training group participated in a 6-week strength-training protocol using rubber tubing 3 times a week throughout the training period . The control group did not participate in the strength-training protocol . SUBJECTS Twenty healthy college students ( 10 females , 10 males , age = 20.6 + /- 2.23 years ; ht = 176.40 + /- 7.14 cm ; wt = 74.18 + /- 10.17 kg ) with a history of functional ankle instability volunteered to participate in this study . MEASUREMENTS We pretested and posttested dorsiflexor and evertor isometric strength with a h and held dynamometer and collected joint position sense ( JPS ) data at 20 degrees for inversion and plantar flexion and at 10 degrees for eversion and dorsiflexion . RESULTS Statistical tests for strength and JPS revealed significant group-by-time interactions for dorsiflexion strength , eversion strength , inversion JPS , and plantar flexion JPS . Simple main-effects testing revealed improvements in training group strength and JPS at posttesting . There were no significant effects for eversion JPS , but the group main effect for dorsiflexion JPS was significant , with the experimental group having better scores than the control group . CONCLUSIONS Ankle-strengthening exercises improved strength , inversion JPS , dorsiflexion JPS , and plantar flexion JPS in subjects with functionally unstable ankles PURPOSE The aim of the present study was to investigate the effects of a 6-wk multi-station proprioceptive exercise program that is easy to integrate in normal training programs . METHODS Patients with chronic ankle instability were used , and results of three testing procedures before and afterward were compared : joint position sense , postural sway , and muscle reaction times to sudden inversion events on a tilting platform . A total of 30 subjects with 48 unstable feet were evaluated ( exercise group : N = 31 ; control group : N = 17 ) . RESULTS In the exercise group , the results showed a significant improvement in joint position sense and postural sway as well as significant changes in muscle reaction times . CONCLUSION Based on the present results , a multi-station proprioceptive exercise program can be recommended for prevention and rehabilitation of recurrent ankle inversion injuries Abstract Twenty-one subjects with functional ankle instabilities were provided with an ankle support for all athletic and other physical activities for 3 months . St and ardized tests were carried out at the beginning and after 3 weeks , 6 weeks , and 3 months . The following evaluation methods were used : KAT-2000 ( static and dynamic ) , side stepping over 8 m , isokinetic force ( Cybex 6000 ) , angle reproduction test , SF-36 score , and Weber ankle score . Use of the ankle support improved both sensomotor and sport-specific abilities , particularly regarding dynamic requirements such as in the dynamic KAT-2000 test . Subjects using the support with functional ankle instability also demonstrated improved sport-specific capabilities such as those required in the fast side-step run . We observed no negative effect on sport-specific skills requiring joint stabilization isokinetic strength , even after 3 months . This was also the case with mobility in the talocrural joint and speed in the side-step run . Our findings demonstrate that even after 3 months there are no detrimental effects on sport-specific skills that require joint stabilization |
12,421 | 17,457,793 | Various aspects of caregivers ' mental health and burden were studied .
Best results were obtained regarding general mental health .
Other aspects often showed modest and varying results .
Caregivers ' competence was less often addressed .
The effects on the cognitive and physical functioning , behavioural problems and survival of the persons with dementia were modest and inconsistent , whereas their mental health is positively affected and admittance to long stay care is often delayed .
Combined programmes may improve some , not all , aspects of functioning for caregiver and person with dementia . | OBJECTIVE This study review s the evidence for effects of combined intervention programmes for both the informal caregiver and the person with dementia . | All dementia patients and their caregivers who had received a University-based comprehensive evaluation and a diagnosis of Alzheimer 's disease during 1997 ( N = 80 ) were surveyed 1 year after their initial assessment . Of the original cohort , 72.5 % were contacted , and two subgroups were defined : 31 patients were being seen only by their primary care physicians ( MED ) , and 27 patients were being treated in addition by a geriatric psychiatry faculty member ( GERO ) . There were statistically significant differences between the two groups ( MED vs. GERO , respectively ) at follow-up in terms of : 1 ) hospitalization ( 39 % vs. 15 % ; P < O.05 ) ; 2 ) cognitive status ( P < O.05 ) ; and 3 ) prescription of donepezil at follow-up ( 35 % vs. 64 % ; P < O. 005 ) . These differences need to be assessed in a larger-scale prospect i ve study PURPOSE OF STUDY The authors determined short-term effects of a home environmental intervention on self-efficacy and upset in caregivers and daily function of dementia patients . They also determined if treatment effect varied by caregiver gender , race , and relationship to patient . DESIGN AND METHODS Families ( N = 171 ) of dementia patients were r and omized to intervention or usual care control group . The intervention involved 5 90-min home visits by occupational therapists who provided education and physical and social environmental modifications . RESULTS Compared with controls , intervention caregivers reported fewer declines in patients ' instrumental activities of daily living ( p = .030 ) and less decline in self-care and fewer behavior problems in patients at 3 months post-test . Also , intervention spouses reported reduced upset ( p = .049 ) , women reported enhanced self-efficacy in managing behaviors ( p = .038 ) , and women ( p = .049 ) and minorities ( p = .037 ) reported enhanced self-efficacy in managing functional dependency . IMPLICATION S The environmental program appears to have a modest effect on dementia patients ' IADL dependence . Also , among certain subgroups of caregivers the program improves self-efficacy and reduces upset in specific areas of caregiving STUDY QUESTION Did the Medicare Alzheimer 's Disease Demonstration , with its goal of improving caregiver outcomes through case management and subsidized community services , affect the nursing home entry rate of treatments with dementia compared to controls ? DATA SOURCES Interviews conducted at baseline and six months thereafter . Measures include date of nursing home entry , client and caregiver health , and income . STUDY DESIGN The demonstration r and omly assigned voluntary applicants into treatment and control groups . Treatment group cases were eligible for case management and for an 80 percent discount on community care benefits , up to about $ 600 per month . DATA COLLECTION All cases received baseline and semi-annual assessment interviews for up to three years after enrollment . Analyses are among cases that remained in the demonstration for more than 30 days after enrollment ( n = 8,095 ) . PRINCIPAL FINDINGS The intervention of case management and subsidized community service had no effect on nursing home entry rates for treatments overall , compared to those of controls , and few effects on treatment subgroups , with the exception of one site where it may have increased nursing home entry rates . CONCLUSIONS Providing case management and subsidized community services with the goal of improving caregiver outcomes may have little effect on nursing home entry rates for people with dementia The current study is a controlled clinical investigation of two nonpharmacological treatments of depression in patients with Alzheimer 's disease . Two active behavioral treatments , one emphasizing patient pleasant events and one emphasizing caregiver problem solving , were compared to an equal- duration typical care condition and a wait list control . Seventy-two patient-caregiver dyads were r and omly assigned to one of four conditions and assessed pre- , post- , and at 6-months follow-up . Patients in both behavioral treatment conditions showed significant improvement in depression symptoms and diagnosis as compared with the two other conditions . These gains were maintained at 6-month follow-up . Caregivers in each behavioral condition also showed significant improvement in their own depressive symptoms , while caregivers in the two other conditions did not . Results indicate that behavioral interventions for depression are important and effective strategies for treating demented patients and their caregivers OBJECTIVE --To reduce the psychological stress and improve the skills in coping of people who care for relatives with dementia . DESIGN -- Assessment and suitability of carers by question naire ; assessment of patients and carers in a hospital outpatient clinic ; allocation to groups according to date of application to study . Linkage of groups of four carers and programme coordinator by telephone conference calls over 12 months after programmes . Re assessment at three , six , 12 , and , for those in the " wait list " group , 18 months . SETTING --The programmes were conducted in the psychiatry unit of a Sydney teaching hospital . SUBJECTS -- Eligible patients were less than 80 years old , had mild to moderate dementia , and lived at home with their carer . Of the 96 patient-carer pairs in the study , 33 were in the dementia carers ' programme group , 31 were in the memory retraining group , and 32 were in the wait list group . INTERVENTIONS --Carers in the dementia carers ' programme received training in coping with the difficulties of looking after patients with dementia while the patients had sessions in subjects such as memory retraining . In the memory retraining programme patients were admitted and received the patient component of the carers ' programme while their carers had 10 days ' respite . In the wait list group carers waited six months before undertaking the carers ' programme . MAIN OUTCOME MEASURES --Effect of the programmes on carers ' general health question naire scores and the rate of placement of patients in institutions . RESULTS --At 12 months ' follow up the carers ' programme had result ed in significantly lower psychological stress among carers than the memory retraining programme ( mean ( SD ) general health question naire scores at 0 months were 6.31 ( 6.23 ) and 3.60 ( 6.25 ) respectively , and at 12 months were 4.69 ( 5.58 ) and 7.40 ( 9.39 ) ; p less than 0.05 . ) In the wait list group distress scores remained stable , even after the carers and patients had undertaken the carers ' programme . Patients deteriorated over 12 months regardless of group allocation , but at 30 months , allowing for patients who died and could not be included in the analysis , 65 % of patients in the carers ' programme group were still living at home compared with 26 % in the memory retraining programme group . CONCLUSION --The intensive intervention programme described for carers of patients with dementia can reduce the psychological morbidity of the carer and delay the placement of the patient in an institution without increasing the use of health services by either patient or carer A r and omized 3-year study assessed the effect of exp and ed community-based services and case management on 5,254 caregivers of dementia clients . A tested policy concern was whether the financing of formal care would result in a reduction of informal assistance . Unmet needs task assistance for the demonstration 's treatment group caregivers decreased by 30 percent within 6 months and by about 20 percent over 36 months relative to controls . While treatment group members used slightly more formal care over time , there were no differences between treatment and control groups in primary caregiver hours after 36 months , or in the number of tasks in which primary or secondary caregivers provided assistance OBJECTIVE To determine the effects of attendance at a memory clinic on the psychosocial health of carers . DESIGN R and omized control trial . PARTICIPANTS Fifty community dwelling subjects with mild to moderate dementia and their carers . MAIN OUTCOME MEASURES Carer burden , psychological morbidity and psychosocial health related quality of life at 6 and 12 months post intervention . MAIN RESULTS There was significant improvement in psychosocial health related quality of life of carers as measured by the psychosocial domain of the Functional Limitation Profile ( FLP ) at 6 months ( p < 0.01 ) , including improvement in the subgroups of alertness behaviour ( p < 0.05 ) and social interaction ( p < 0.01 ) , after adjustment for age of subject and baseline scores . The improvement in social interaction was maintained at 12 months ( p < 0.05 ) . There was no significant difference in carer psychological morbidity ( General Health Question naire ) , carer burden ( Zarit family interview ) or carer knowledge of dementia ( Dementia Knowledge Test ) at 6 or 12 months , between groups . CONCLUSIONS These results demonstrate improved psychosocial health related quality of life for carers of those with mild to moderate cognitive impairment attending a memory clinic . Further research in this area is indicated , comparing memory clinic intervention with alternative support PURPOSE We examine 6-month effects of the Environmental Skill-Building Program on caregiver well-being and care recipient functioning and whether effects vary by caregiver gender , race ( White or non-White ) , and relationship ( spouse or nonspouse ) . DESIGN AND METHODS We enrolled 255 family caregivers of community-residing persons with Alzheimer 's disease or related disorders , of whom 190 participated in a follow-up interview . Caregivers were r and omized to a usual care control group or intervention group that received five home contacts and one telephone contact by occupational therapists , who provided education , problem-solving training , and adaptive equipment . Baseline and 6-month follow-up included self-report measures of caregiver objective and subjective burden , caregiver well-being , and care recipient problem behaviors and physical function . RESULTS Compared with controls ( n = 101 ) , intervention caregivers ( n = 89 ) reported less upset with memory-related behaviors , less need for assistance from others , and better affect . Intervention spouses reported less upset with disruptive behaviors ; men reported spending less time in daily oversight ; and women reported less need for help from others , better affect , and enhanced management ability , overall well-being , and mastery relative to control group counterparts . Statistically significant treatment differences were not found for hours helping with instrumental activities of daily living , upset with providing assistance with instrumental activities of daily living and activities of daily living , perceived change in somatic symptoms , White versus non-White caregivers , or care recipient outcomes . IMPLICATION S The Environmental Skill-Building Program reduces burden and enhances caregiver well-being in select domains and has added benefit for women and spouses CONTEXT Exercise training for patients with Alzheimer disease combined with teaching caregivers how to manage behavioral problems may help decrease the frailty and behavioral impairment that are often prevalent in patients with Alzheimer disease . OBJECTIVE To determine whether a home-based exercise program combined with caregiver training in behavioral management techniques would reduce functional dependence and delay institutionalization among patients with Alzheimer disease . DESIGN , SETTING , AND PATIENTS R and omized controlled trial of 153 community-dwelling patients meeting National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer Disease and Related Disorders Association criteria for Alzheimer disease , conducted between June 1994 and April 1999 . INTERVENTIONS Patient-caregiver dyads were r and omly assigned to the combined exercise and caregiver training program , Reducing Disability in Alzheimer Disease ( RDAD ) , or to routine medical care ( RMC ) . The RDAD program was conducted in the patients ' home over 3 months . MAIN OUTCOME MEASURES Physical health and function ( 36-item Short-Form Health Survey 's [ SF-36 ] physical functioning and physical role functioning subscales and Sickness Impact Profile 's Mobility subscale ) , and affective status ( Hamilton Depression Rating Scale and Cornell Depression Scale for Depression in Dementia ) . RESULTS At 3 months , in comparison with the routine care patients , more patients in the RDAD group exercised at least 60 min/wk ( odds ratio [ OR ] , 2.82 ; 95 % confidence interval [ CI ] , 1.25 - 6.39 ; P = .01 ) and had fewer days of restricted activity ( OR , 3.10 ; 95 % CI , 1.08 - 8.95 ; P<.001 ) . Patients in the RDAD group also had improved scores for physical role functioning compared with worse scores for patients in the RMC group ( mean difference , 19.29 ; 95 % CI , 8.75 - 29.83 ; P<.001 ) . Patients in the RDAD group had improved Cornell Depression Scale for Depression in Dementia scores while the patients in the RMC group had worse scores ( mean difference , -1.03 ; 95 % CI , -0.17 to -1.91 ; P = .02 ) . At 2 years , the RDAD patients continued to have better physical role functioning scores than the RMC patients ( mean difference , 10.89 ; 95 % CI , 3.62 - 18.16 ; P = .003 ) and showed a trend ( 19 % vs 50 % ) for less institutionalization due to behavioral disturbance . For patients with higher depression scores at baseline , those in the RDAD group improved significantly more at 3 months on the Hamilton Depression Rating Scale ( mean difference , 2.21 ; 95 % CI , 0.22 - 4.20 ; P = .04 ) and maintained that improvement at 24 months ( mean difference , 2.14 ; 95 % CI , 0.14 - 4.17 ; P = .04 ) . CONCLUSION Exercise training combined with teaching caregivers behavioral management techniques improved physical health and depression in patients with Alzheimer disease STUDY QUESTION Does improved access to community-based care reduce perceived burden and reported levels of depression among primary caregivers of people with dementia ? DATA SOURCES Baseline and periodic caregiver interviews with participants in the Medicare Alzheimer 's Disease Demonstration . Client and caregiver attributes and caregiver outcomes such as depression and burden scores were among the measures . STUDY DESIGN Applicants to the demonstration ( all voluntary ) were r and omly assigned into treatment and control groups . Treatment group cases were eligible for case management and for up to $ 699 per month in community care benefits . ( The actual monthly entitlement varied among the eight demonstration communities due to regional cost differences and inflation adjustments over the four-year demonstration period . ) DATA COLLECTION A total of 5,307 eligible individuals received a baseline assessment at the time of application to the demonstration and at least one semi-annual re assessment . Clients and their caregivers were periodically reassessed producing a total of 20,707 observations . PRINCIPAL FINDINGS Persons in the treatment group had a high exposure to case management and a greater likelihood of community service use relative to those in the control group . Treatment group membership was associated with statistically significant , but very small reductions in caregiver burden ( in four of eight sites ) and depression ( three of eight sites ) over a 36-month tracking period . These findings are not sustained with all cases combined , or among a higher-re source demonstration model considered separately . CONCLUSIONS Both the fact that these programmatic differences did not translate into substantial treatment group reductions in caregiver burden or depression , and the consistency of these findings with those of prior case management evaluations suggest the need to reformulate this programmatic intervention into areas not previously tested : 24-hour care , crisis intervention , coordination with primary care , or chronic disease management OBJECTIVE To describe the theory , elements and practice of a successful caregiver training programme ; and report the 8-year outcome . DESIGN Prospect i ve , r and omized control trial and longitudinal follow-up over approximately 8 years . SETTING Psychiatry unit , general teaching hospital , Sydney , Australia . PARTICIPANTS 96 persons less than 80 years old with mild to moderate dementia and their cohabiting caregivers . INTERVENTIONS All patients received a 10-day structured memory retraining and activity programme . Caregivers in the immediate and wait-list caregiver training groups received a structured , residential , intensive 10-day training programme , boosted by follow-ups and telephone conferences over 12 months . Those in the wait-list group entered the programme after waiting 6 months . The third group of caregivers received 10 days ' respite ( while patients underwent their memory retraining programme ) and 12 months booster sessions as for the other groups . MAIN OUTCOME MEASURES Nursing home admission ; time until patient death . MAIN RESULTS 64 % of patients whose caregivers were in the immediate training group , 53 % of wait-list group patients and 70 % of memory retraining patients had died . Nursing home admission had occurred in 79 % of the immediate training , 83 % of the delayed and 90 % of the memory retraining group . Eight-year survival analysis indicated that patients whose caregivers received training stayed at home significantly longer ( p = 0.037 ) and tended to live longer ( p = 0.08 ) . CONCLUSIONS Caregiver training programmes demonstrably can delay institutionalization of people with dementia OBJECTIVES To determine whether community care of demented patients can be prolonged by means of a 2-year support program based on nurse case management . DESIGN R and omized controlled intervention study with 2-year follow-up . SETTING Demented patients entitled to payments from the Social Insurance Institution for community care , in five municipalities in eastern Finl and . PARTICIPANTS One hundred demented patients , age 65 and older , living at home with the primary support of informal caregivers , allocated at r and om to the intervention ( n = 53 ) or control group ( n = 47 ) . INTERVENTION Intervention patients and their caregivers were provided with a 2-year intervention program of systematic , comprehensive support by a dementia family care coordinator . MEASUREMENTS Time to institutionalization ( period in community care ) from enrollment of patients in the study to their placement in long-term institutional care . RESULTS During the first months , the rate of institutionalization was significantly lower in the intervention group than in the control group ( P = .042 ) , but the benefit of the intervention decreased with time ( P = .028 ) . Estimated probability of staying in community care up to 6 , 12 , and 24 months was 0.98 , 0.92 , and 0.63 in the intervention group and 0.91 , 0.81 , and 0.68 in the control group , respectively . Results also suggest that the intervention used in the study might be especially beneficial to patients with severe dementia and those with problems threatening the continuity of community care . CONCLUSIONS The placement of demented patients in long-term institutional care can be deferred with the support of a dementia family care coordinator . However , by the end of the 2-year intervention , the number of patients institutionalized was similar in the intervention and control group . It seems to be beneficial to direct this type of intensive support at severely demented patients and their caregivers . On the basis of our experiences , we suggest that intervention by a dementia family care coordinator should be targeted especially at patients with problems threatening the continuity of community care This 3-year r and omized clinical trial tested the effectiveness of an interdisciplinary psychoeducational family group intervention in decreasing the caregivers ' perceptions of the frequency and severity of behavioral problems in persons with dementia and their reactions to those problems , and in decreasing caregiver burden and depression . The intervention consisted of seven weekly , 2-hour multimedia training sessions that included education , family support , and skills training for 94 primary caregivers and their families . Repeated measures ANOVA was used to test for significant differences between the intervention and waiting list control groups over a 5-month period . The intervention was successful in reducing caregivers ' negative reactions to disruptive behaviors and in reducing caregiver burden over time |
12,422 | 27,640,992 | CONCLUSIONS Based on this review , sufficiently vali date d QIs can be selected for measuring the quality of CKD care . | BACKGROUND AND OBJECTIVES Quality indicators ( QIs ) can be used for measuring the quality of actions of healthcare providers .
This systematic review gives an overview of such QIs measuring processes of care for chronic kidney disease ( CKD ) , and identifies the QIs that have content , face , operational and /or predictive validity . | Background Quality indicators ( QIs ) are an important tool for improving clinical practice and are increasingly being developed from evidence -based guideline recommendations . We aim ed to identify , select and apply guideline recommendations to develop a set of QIs to measure the implementation of evidence -based practice using routinely recorded clinical data in United Kingdom ( UK ) primary care . Methods We review ed existing national clinical guidelines and QIs and used a four-stage consensus development process to derive a set of ‘ high impact ’ QIs relevant to primary care based upon explicit prioritisation criteria . We then field tested the QIs using remotely extracted , anonymised patient records from 89 r and omly sample d primary care practice s in the Yorkshire region of Engl and . Results Out of 2365 recommendations and QIs originally review ed , we derived a set of 18 QIs ( 5 single , 13 composites – comprising 2–9 individual recommendations ) for field testing . QIs predominantly addressed chronic disease management , in particular diabetes , cardiovascular and renal disease , and included both processes and outcomes of care . Field testing proved to be critical for further refinement and final selection . Conclusions We have demonstrated a rigorous and transparent methodology to develop a set of high impact , evidence -based QIs for primary care from clinical guideline recommendations . While the development process was successful in developing a limited set of QIs , it remains challenging to derive robust new QIs from clinical guidelines in the absence of established systems for routine , structured recording of clinical care BACKGROUND Patients with chronic kidney disease ( CKD ) are at significant risk for cardiovascular disease ( CVD ) . The National Kidney Foundation developed clinical practice guidelines ( Kidney Disease Outcomes Quality Initiative ) for targeting low-density lipoprotein cholesterol ( LDL-C ) goals . OBJECTIVE This study evaluated the extent to which these guidelines were adhered to among patients with CKD and to examine factors associated with the attainment of LDL-C goals . METHODS In this cross-sectional study we evaluated patients with a glomerular filtration rate of 15 to 59 mL/min per 1.73 m² . Patients with previous CVD , who were receiving dialysis , or were post kidney transplant were excluded . Administrative data bases were used to determine the percentage of patients with a fasting lipid profile performed within the previous year , the percentage who attained a LDL-C goal less than 100 mg/dL , and to determine lipid-lowering medications prescribed . Logistic regression analysis was used to identify factors associated with LDL-C goal attainment . RESULTS Of the 4541 patients evaluated , 3157 ( 69.5 % ) had a fasting lipid profile performed within the previous year . Overall , 60.8 % attained a LDL-C less than 100 mg/dL. Among patients at goal , 72.2 % were taking lipid-lowering therapy compared with 37.9 % of those not at goal ( P < .01 ) . Characteristics independently associated with LDL-C goal attainment were increasing age , male gender , increasing chronic disease score , history of diabetes , and statin use . CONCLUSION Although most patients were screened and attained LDL-C goal , there was room for improvement . Statin use was independently associated with LDL-C goal attainment . Future prospect i ve studies should focus on evaluating clinical outcomes of lipid-lowering interventions within the CKD population AIMS The study aim ed to assess the prevalence , quality of screening and treatment of chronic kidney disease ( CKD ) , and their trends between 2001 and 2007 , in French adults with type 2 diabetes ( T2D ) . METHODS The 2007 ENTRED survey r and omly selected , from French medical insurance fund data bases , 8926 adults treated for diabetes who had been reimbursed at least three times over the previous 12 months for oral hypoglycaemic agents or insulin . Medical reimbursement data were extracted and two sets of question naires were mailed , one to all patients ( 48 % response rate ) and the other to their doctors ( 62 % ) . Analyses were restricted to the 3894 responders with T2D ( 2232 with data from their doctors ) . Trends between the 2001 and 2007 ENTRED surveys were studied . RESULTS Participants ' mean age was 66 years . The prevalence of CKD was estimated to be at least 29 % , based on doctors ' data ( missing data included ) . Overall , only 17 % had no cl aims for serum creatinine measurements during the year , and 71 % had no cl aims for albuminuria tests ; nonetheless , both figures had decreased from 2001 . Older people , those who lived alone and those who felt poorly informed about diabetes were more likely to have made no cl aims for CKD screening . Assessment of quality of care ( prescribing antihypertensive treatment when indicated ) was possible for 66 % of responders , of whom 25 % did not receive such treatment . CONCLUSION CKD is frequently seen in patients with T2D and is likely to be underestimated because albuminuria screening remains inadequate , despite significant improvements since 2001 . Further efforts are needed to improve CKD screening , patient and doctor awareness , and adequate use of antihypertensive/nephroprotective medications Cardiovascular disease ( CVD ) is a major cause of morbidity and mortality among patients with chronic renal insufficiency ( CRI ) . beta-Adrenergic blockers , acetylsalicylic acid ( ASA ) , angiotensin-converting enzyme ( ACE ) inhibitors , and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) all reduce CVD mortality , but little is known about the extent to which these medications are used in patients with CRI . This study , a prospect i ve cross-sectional study of consecutive patients seen by nephrologists in four Canadian centers for follow-up of progressive CRI in 1999 , was performed to investigate the prevalence of coronary risk factors and use of cardioprotective medications among patients with CRI . Patients had creatinine clearances of 75 mL/min or less but were not on dialysis therapy . Three hundred four consecutive patients meeting the inclusion criteria were enrolled . Mean age was 60.8 + /- 15.7 years , mean creatinine clearance was 30.3 + /- 18 mL/min , and the case mix of kidney diseases was similar to that in the Canadian Organ Replacement Registry data . One hundred seventeen of 304 patients ( 38.5 % ) had a history of previous CVD , and the prevalence of CVD was greater in patients with more severe CRI . Two hundred forty-three patients ( 79.9 % ) had a history of hypertension , 132 patients ( 43.4 % ) had hyperlipidemia , 114 patients ( 37.5 % ) had diabetes mellitus , and 71 patients ( 27.3 % ) were smokers . Thirty-five percent of the patients with CVD had blood pressures greater than 140/90 mm Hg ; 103 patients ( 33.9 % ) were administered beta-blockers ; 196 patients ( 64.5 % ) , ACE inhibitors or angiotensin-receptor blockers ; 83 patients ( 27.3 % ) , ASA ; and 56 patients ( 18.4 % ) , statins . Patients with diabetes were not more likely than those without diabetes to be prescribed cardioprotective medications . CVD is common in the predialysis population , and its prevalence increases with more severe kidney failure . Despite this , the use of cardioprotective medications is relatively low , and many patients had suboptimal blood pressure control . Given the high burden of disease in these patients , beta-blockers and ACE inhibitors should be used to control hypertension and /or for cardioprotection , and the increased use of ASA and statins should be considered BACKGROUND Current recommendations for the management of chronic renal insufficiency ( CRI ) include the use of angiotensin-converting enzyme inhibitors ( ACEI ) and achieving target blood pressure control . We design ed this study to describe the use of these therapeutic strategies , and to investigate barriers to their implementation . METHODS This was a prospect i ve study of 304 consecutive CRI patients , seen at follow-up in four nephrology clinics across Canada . The use of blood pressure control and antihypertensive medication ( AHM ) in each of these clinics was recorded , and a question naire was administered to nephrologists to determine the basis for decisions concerning AHM regimens and ACEI use/non-use . RESULTS Mean age was 60.8+/-15.7 years , mean creatinine clearance was 30.3+/-18 ml/min , and underlying renal diseases were similar to registry data . Mean arterial pressure ( MAP ) achieved was 99.4+/-14.4 and 98.9+/-11.9 mmHg in individuals with > 1 and < /=1 g/day proteinuria , respectively . When similarly stratified by proteinuria , mean systolic blood pressures were 141.4+/-23.5 and 140.9+/-20.3 mmHg , and mean diastolic blood pressures were 78.4+/-14.0 and 77.9+/-11.4 mmHg , respectively . Blood pressure control , according to published guidelines , was achieved in 128 patients ( 42.1 % ) . A further 86 ( 28.3 % ) patients had their AHM increased . The remaining 90 ( 29.6 % ) did not have their AHM increased . Of these , 40 were labelled ' at target blood pressure ' ( mean MAP 100.5+/-5.4 mmHg ) , 19 ' office hypertension ' and 11 ' unfavourable risk/benefit ratios ' . There were 108/304 ( 35.5 % ) patients who were not taking ACEI or ARB ( angiotensin receptor antagonist ) : 34/108 ( 31 % ) had previous ACEI failure due to hyperkalaemia ( 21/108 , 19 % ) or acute renal failure ( 17/108 , 16 % ) , and 61/108 ( 55 % ) were felt ' unlikely to benefit ' ( categories not mutually exclusive ) . Miscommunication with the primary physician and medication costs were not identified as significant barriers to improved blood pressure control or ACEI use . CONCLUSIONS Approximately 40 % of CRI patients are achieving current blood pressure goals and 64 % are prescribed ACEI/ARB in tertiary care nephrology clinics . Although the use of these strategies may be increasing , there remains room for improvement . Physicians should remain aware of the need to use these proven strategies in patients with CRI BACKGROUND The implementation of national estimated glomerular filatration rate reporting and the inclusion of renal-specific indicators in a primary care pay for performance ( P4P ) system since April 2006 has promoted identification and better management of risk factors related to chronic kidney disease ( CKD ) . In the UK , the P4P framework is known as the Quality and Outcomes Framework ( QOF ) . One of the key targets for intervention in primary care was hypertension . It is clear that hypertension is a major predictor of development and progression of CKD ; thus , targeting better blood pressure control is likely to have a positive impact on outcomes in CKD . The aim of this study was to evaluate the effectiveness of renal indicators outlined in P4P on the management of hypertension in primary care . To estimate the cost implication s of the result ing changes in prescribing patterns of antihypertensive medication following introduction of such indicators . METHODS We performed a prospect i ve cohort study using a large primary care data base . This cohort was taken from a data base collated as part of a clinical decision support system used to assist the management of CKD in primary care . We investigated a total population of 90 250 individuals on general practitioner ( GP ) registers with a valid serum creatinine estimation in the 6-year study period . A total of 10 040 patients had confirmed stage 3 - 5 CKD in the 2 years pre-QOF and formed the study cohort . Patients were studied over three time periods , pre-QOF ( 1 April 2004 to 31 March 2006 ) , 2 years post-QOF ( 1 April 2006 to 31 March 2008 ) and finally the two subsequent years ( 1 April 2008 to 31 March 2010 ) . The mean systolic and diastolic blood pressures ( BP ) together with antihypertensive medication were analysed over the three time periods . Cost calculation was based on 2009 British National Formulary list prices for antihypertensives . RESULTS The mean age of the cohort at the start of the study period was 64.8 years , 55 % were female . In those patients with stage 3 - 5 CKD 83.9 % were hypertensive , defined by a pre-P4P BP of > 140/85 or currently taking antihypertensive medication . The proportion of patients with CKD 3 - 5 attaining the BP target of 145/80 increased from 41.5 % in the pre-QOF period to 50.0 % in the post-QOF period . This increase was even more marked for those with hypertension in the pre-QOF period ( 28.8 - 45.1 % ) . In the hypertensive patients , mean BP fell from 146/79 mmHg to 140/76 in the first 2 years post-P4P [ P < 0.01 , analysis of variance ( ANOVA ) ] . This BP reduction was sustained in the last 2 years of the study , 139/75 ( P < 0.01 , ANOVA ) . The proportion of hypertensive patients taking angiotensin-converting enzyme inhibitors or angiotensin blockers increased , this was also sustained in the third time period . An increase in the prescribing of diuretics , calcium channel blockers and β-blockers was also observed . The additional cost of increased prescribing was calculated to be € 25.00 per hypertensive patient based on GP prescription data . CONCLUSIONS Population BP control has improved since the introduction of P4P renal indicators , and this improvement has been sustained . This was associated with a significant increase in the use of antihypertensive medication , result ing in increased prescription cost . Longer-term follow-up will establish whether or not this translates to improved outcomes in terms of progression of CKD , cardiovascular disease and patient mortality BACKGROUND Explicit criteria for judging medication safety and use issues in patients with chronic kidney disease ( CKD ) are lacking . STUDY DESIGN Quality improvement report . SETTING & PARTICIPANTS Nephrologists ( n = 4 ) , primary care physicians ( n = 2 ) , hospital pharmacists with expertise in nephrology ( n = 4 ) , and community pharmacists ( n = 2 ) . The PAIR ( Pharmacotherapy Assessment in Chronic Renal Disease ) criteria were applied retrospectively to 90 patients with CKD in a r and omized study . QUALITY IMPROVEMENT PLAN Development of an explicit set of criteria to enable rapid and systematic detection of drug-related problems ( DRPs ) . Using a R AND method , experts judged the clinical significance of DRPs and the appropriateness of a community pharmacist intervention . The PAIR criteria include 50 DRPs grouped into 6 categories . OUTCOMES DRPs detected using the PAIR criteria compared with implicit clinical judgment by nephrology pharmacists . MEASUREMENTS Prevalence of DRPs and reliability , validity , and responsiveness of the PAIR criteria . RESULTS A mean of 2.5 DRPs/patient ( 95 % CI , 2.0 - 3.1 ) was identified based on the PAIR criteria compared with 3.9 DRPs/patient ( 95 % CI , 3.4 - 4.5 ) based on clinical judgment of nephrology pharmacists . Inter-rater reliability coefficients ( κ ) by PAIR category varied from 0.80 - 1.00 , with an intraclass correlation coefficient ( ICC ) of 0.93 ( 95 % CI , 0.89 - 0.95 ) for total DRPs per patient . Test-retest reliability coefficients by category varied from 0.74 - 1.00 , with an ICC of 0.91 ( 95 % CI , 0.82 - 0.96 ) for total DRPs per patient . During the study , the mean number of DRPs per patient did not change significantly when assessed using the PAIR criteria and clinical judgment . LIMITATION The prevalence of PAIR DRPs may be underestimated due to the retrospective nature of the validation . CONCLUSION The prevalence of DRPs requiring the intervention of community pharmacists is high in patients with CKD . The PAIR criteria are reliable , but their responsiveness remains to be shown |
12,423 | 25,115,635 | Some GLP-1RAs , especially liraglutide—1.8 mg once daily and liraglutide—1.2 mg once daily , were associated with a significant reduction in waist circumference | Glucagon-like peptide-1 receptor agonists ( GLP-1RAs ) are increasingly used in patients with type 2 diabetes .
However , the effect on abdominal obesity has not yet been confirmed .
The study aim ed to systematic ally evaluate the effect of GLP-1RAs on waist circumference in patients with type 2 diabetes . | OBJECTIVE Study the effects of exenatide ( EXE ) plus rosiglitazone ( ROSI ) on β-cell function and insulin sensitivity using hyperglycemic and euglycemic insulin clamp techniques in participants with type 2 diabetes on metformin . RESEARCH DESIGN AND METHODS In this 20-week , r and omized , open-label , multicenter study , participants ( mean age , 56 ± 10 years ; weight , 93 ± 16 kg ; A1C , 7.8 ± 0.7 % ) continued their metformin regimen and received either EXE 10 μg b.i.d . ( n = 45 ) , ROSI 4 mg b.i.d . ( n = 45 ) , or EXE 10 μg b.i.d . + ROSI 4 mg b.i.d . ( n = 47 ) . Seventy-three participants underwent clamp procedures to quantitate insulin secretion and insulin sensitivity . RESULTS A1C declined in all groups ( P < 0.05 ) , but decreased most with EXE+ROSI ( EXE+ROSI , −1.3 ± 0.1 % ; ROSI , −1.0 ± 0.1 % , EXE , −0.9 ± 0.1 % ; EXE+ROSI vs. EXE or ROSI , P < 0.05 ) . ROSI result ed in weight gain , while EXE and EXE+ROSI result ed in weight loss ( EXE , −2.8 ± 0.5 kg ; EXE+ROSI , −1.2 ± 0.5 kg ; ROSI , + 1.5 ± 0.5 kg ; P < 0.05 between and within all groups ) . At week 20 , 1st and 2nd phase insulin secretion was significantly higher in EXE and EXE+ROSI versus ROSI ( both P < 0.05 ) . Insulin sensitivity ( M value ) was significantly higher in EXE+ROSI versus EXE ( P = 0.014 ) . CONCLUSIONS Therapy with EXE+ROSI offset the weight gain observed with ROSI and elicited an additive effect on glycemic control with significant improvements in β-cell function and insulin sensitivity OBJECTIVE Glucagon-like peptide (GLP)-1 is a gut hormone that exerts incretin effects and suppresses food intake in humans , but its therapeutic use is limited due to its short half-life . This was a r and omized , double-blind , parallel-group , placebo-controlled trial investigating the effect of the long-acting GLP-1 derivative liraglutide ( NN2211 ) on glycemic control , body weight , body composition , and 24-h energy expenditure in obese subjects with type 2 diabetes . RESEARCH DESIGN AND METHODS Thirty-three patients ( mean + /- SD ) aged 60.0 + /- 9.5 years , with HbA(1c ) 7.5 + /- 1.2 % and BMI 36.6 + /- 4.1 kg/m(2 ) , were r and omized to treatment with a single daily subcutaneous dose of 0.6 mg liraglutide ( n = 21 ) or placebo ( n = 12 ) for 8 weeks . In addition to weight and glycemic parameters , body composition was assessed by dual-energy X-ray absorptiometry ( DEXA ) scanning and 24-h energy expenditure in a respiratory chamber . RESULTS After 8 weeks , liraglutide reduced fasting serum glucose ( liraglutide , -1.90 mmol/l , and placebo , 0.27 mmol/l ; P = 0.002 ) and HbA(1c ) ( liraglutide , -0.33 % , and placebo , 0.47 % ; P = 0.028 ) compared with placebo . No change in body weight was detected ( liraglutide , -0.7 kg , and placebo , -0.9 kg ; P = 0.756 ) . There was a nonsignificant trend toward a decrease in total fat mass ( liraglutide , -0.98 % , and placebo , -0.12 % ; P = 0.088 ) and toward an increase in lean body mass ( liraglutide , 1.02 % , and placebo , 0.23 % ; P = 0.118 ) in the liraglutide group compared with the placebo group . Twenty-four-hour energy expenditure was unaffected by the treatment ( liraglutide , -12.6 kJ/h , and placebo , -13.7 kJ/h ; P = 0.799 ) . CONCLUSIONS Eight weeks of 0.6-mg liraglutide treatment significantly improved glycemic control without increasing weight in subjects with type 2 diabetes compared with those on placebo . No influence on 24-h energy expenditure was detected Aim The aim of this study was to compare the efficacy and safety of once-daily human glucagon-like peptide-1 analogue liraglutide with dipeptidyl peptidase-4 inhibitor sitagliptin , each added to metformin , over 52 weeks in individuals with type 2 diabetes . Methods In an open-label , parallel-group trial , metformin-treated participants were r and omised to liraglutide 1.2 mg/day ( n= 225 ) , liraglutide 1.8 mg/day ( n= 221 ) or sitagliptin 100 mg/day ( n= 219 ) for 26 weeks ( main phase ) . Participants continued the same treatment in a 26-week extension . Results Liraglutide ( 1.2 or 1.8 mg ) was superior to sitagliptin for reducing HbA1c from baseline ( 8.4–8.5 % ) to 52 weeks : −1.29 % and −1.51 % vs. −0.88 % respectively . Estimated mean treatment differences between liraglutide and sitagliptin were as follows : −0.40 % ( 95 % confidence interval −0.59 to −0.22 ) for 1.2 mg and −0.63 % ( −0.81 to −0.44 ) for 1.8 mg ( both p < 0.0001 ) . Weight loss was greater with liraglutide 1.2 mg ( −2.78 kg ) and 1.8 mg ( −3.68 kg ) than sitagliptin ( −1.16 kg ) ( both p < 0.0001 ) . Diabetes Treatment Satisfaction Question naire scores increased significantly more with liraglutide 1.8 mg than with sitagliptin ( p = 0.03 ) . Proportions of participants reporting adverse events were generally comparable ; minor hypoglycaemia was 8.1 % , 8.3 % and 6.4 % for liraglutide 1.2 mg , 1.8 mg and sitagliptin respectively . Gastrointestinal side effects , mainly nausea , initially occurred more frequently with liraglutide , but declined after several weeks . Conclusion Liraglutide provides greater sustained glycaemic control and body weight reduction over 52 weeks . Treatment satisfaction was significantly greater with 1.8 mg liraglutide , similar to 26-week results . The safety profiles of liraglutide and sitagliptin are consistent with previous reports OBJECTIVE This multicenter , open-label , parallel-arm study compared the efficacy and safety of exenatide once weekly ( EQW ) with titrated insulin detemir in patients with type 2 diabetes inadequately controlled with metformin ( with or without sulfonylureas ) . RESEARCH DESIGN AND METHODS Patients were r and omized to EQW ( 2 mg ) or detemir ( once or twice daily , titrated to achieve fasting plasma glucose ≤5.5 mmol/L ) for 26 weeks . The primary outcome was proportion of patients achieving A1C ≤7.0 % and weight loss ≥1.0 kg at end point , analyzed by means of logistic regression . Secondary outcomes included measures of glycemic control , cardiovascular risk factors , and safety and tolerability . RESULTS Of 216 patients ( intent-to-treat population ) , 111 received EQW and 105 received detemir . Overall , 44.1 % ( 95 % CI , 34.7–53.9 ) of EQW-treated patients compared with 11.4 % ( 6.0–19.1 ) of detemir-treated patients achieved the primary outcome ( P < 0.0001 ) . Treatment with EQW result ed in significantly greater reductions than detemir in A1C ( least-square mean ± SE , −1.30 ± 0.08 % vs. −0.88 ± 0.08 % ; P < 0.0001 ) and weight ( −2.7 ± 0.3 kg vs. + 0.8 ± 0.4 kg ; P < 0.0001 ) . Gastrointestinal-related and injection site – related adverse events occurred more frequently with EQW than with detemir . There was no major hypoglycemia in either group . Five ( 6 % ) patients in the EQW group and six ( 7 % ) patients in the detemir group experienced minor hypoglycemia ; only one event occurred without concomitant sulfonylureas ( detemir group ) . CONCLUSIONS Treatment with EQW result ed in a significantly greater proportion of patients achieving target A1C and weight loss than treatment with detemir , with a low risk of hypoglycemia . These results suggest that EQW is a viable alternative to insulin detemir treatment in patients with type 2 diabetes with inadequate glycemic control using oral antidiabetes drugs Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed OBJECTIVE We recently reported that after 26 weeks , exenatide once weekly ( EQW ) result ed in superior A1C reduction , reduced hypoglycemia , and progressive weight loss compared with daily insulin glargine ( IG ) in patients with type 2 diabetes who were taking metformin alone or with sulfonylurea . This 84-week extension study assessed the long-term safety and efficacy of EQW versus IG . RESEARCH DESIGN AND METHODS This multicenter , open-label , r and omized , two-arm , parallel trial assessed change in A1C , proportions of patients achieving A1C < 7.0 and ≤6.5 % , body weight , incidence of hypoglycemia , and overall safety . RESULTS Of 415 patients who completed 26 weeks , 390 ( 194 EQW and 196 IG patients ) entered the extension study . At 84 weeks , A1C decreased from baseline ( 8.3 % ) by −1.2 % for EQW vs. −1.0 % for IG ( P = 0.029 ) . The proportions of patients who achieved end point A1C targets < 7.0 and ≤6.5 % were 44.6 % for EQW patients vs. 36.8 % for IG patients ( P = 0.084 ) and 31.3 % for EQW patients vs. 20.2 % for IG patients ( P = 0.009 ) , respectively . Patients taking EQW lost 2.1 kg of body weight , whereas those taking IG gained 2.4 kg ( P < 0.001 ) . Among patients taking metformin plus sulfonylurea , the incidence of minor hypoglycemia was 24 % for EQW patients vs. 54 % for IG patients ( P < 0.001 ) ; among patients taking metformin alone , it was 8 % for EQW patients vs. 32 % for IG patients ( P < 0.001 ) . Among adverse events occurring in ≥5 % of patients , diarrhea and nausea occurred more frequently ( P < 0.05 ) in the EQW group than in the IG group ( 12 vs. 6 % and 15 vs. 1 % , respectively ) . CONCLUSIONS After 84 weeks , patients treated with EQW continued to experience better glycemic control with sustained overall weight loss and a lower risk of hypoglycemia than patients treated with IG OBJECTIVE To determine the effect of a lifestyle modification program plus exenatide versus lifestyle modification program plus placebo on weight loss in overweight or obese participants with type 2 diabetes treated with metformin and /or sulfonylurea . METHODS In this 24-week , multicenter , r and omized , double-blind , placebo-controlled study , 194 patients participated in a lifestyle modification program , consisting of goals of 600 kcal/day deficit and physical activity of at least 2.5 hours/week . Participants were r and omized to 5 microg exenatide twice daily injection + lifestyle modification program ( n = 96 ) or placebo + lifestyle modification program ( n = 98 ) , and after 4 weeks increased their exenatide dose to 10 microg twice daily or volume equivalent of placebo . RESULTS Baseline characteristics : ( mean + /- st and ard deviation ) age , 54.8 + /- 9.5 years ; weight , 95.5 + /- 16.0 kg ; hemoglobin A(1c ) , 7.6 + /- 0.8 % . At 24 weeks ( least squares mean + /- st and ard error ) , treatments showed similar decreases in caloric intake ( -378 + /- 58 vs -295 + /- 58 kcal/day , exenatide + lifestyle modification program vs placebo + lifestyle modification program , P = .27 ) and increases in exercise-derived energy expenditure . Exenatide + lifestyle modification program showed greater change in weight ( -6.16 + /- 0.54 kg vs -3.97 + /- 0.52 kg , P = .003 ) , hemoglobin A(1c ) ( -1.21 + /- 0.09 % vs -0.73 + /- 0.09 % , P < .0001 ) , systolic ( -9.44 + /- 1.40 vs -1.97 + /- 1.40 mm Hg , P < .001 ) and diastolic blood pressure ( -2.22 + /- 1.00 vs 0.47 + /- 0.99 mm Hg , P = .04 ) . Nausea was reported more for exenatide + lifestyle modification program than placebo + lifestyle modification program ( 44.8 % vs 19.4 % , respectively , P < .001 ) , with no difference in withdrawal rates due to adverse events ( 4.2 % vs 5.1 % , respectively , P = 1.0 ) or rates of hypoglycemia . CONCLUSIONS When combined with lifestyle modification , exenatide treatment led to significant weight loss , improved glycemic control , and decreased blood pressure compared with lifestyle modification alone in overweight or obese participants with type 2 diabetes on metformin and /or sulfonylurea treatment OBJECTIVE To study the effect of exenatide on body composition and circulating cardiovascular risk biomarkers . RESEARCH DESIGN AND METHODS Metformin-treated patients with type 2 diabetes ( N = 69 ) were r and omized to exenatide or insulin glargine and treated for 1 year . Body composition was evaluated by dual-energy X-ray absorptiometry . Additionally , body weight , waist circumference , and cardiovascular biomarkers were measured . RESULTS Treatment with exenatide for 1 year significantly reduced body weight , waist circumference , and total body and trunkal fat mass by 6 , 5 , 11 , and 13 % , respectively . In addition , exenatide increased total adiponectin by 12 % and reduced high-sensitivity C-reactive protein by 61 % . Insulin glargine significantly reduced endothelin-1 by 7 % . These changes were statistically independent of the change in total body fat mass and body weight . CONCLUSIONS Exenatide treatment for 1 year reduced body fat mass and improved the profile of circulating biomarkers of cardiovascular risk . No significant changes were seen with insulin glargine except a trend for reduced endothelin-1 levels Objective To assess the efficacy and safety of adding liraglutide to established insulin therapy in poorly controlled Chinese subjects with type 2 diabetes and abdominal obesity compared with increasing insulin dose . Methods A 12-week , r and omized , parallel-group study was carried out . A total of 84 patients completed the trial who had been r and omly assigned to either the liraglutide-added group or the insulin-increasing group while continuing current insulin based treatment . Insulin dose was reduced by 0 - 30 % upon the initiation of liraglutide . Insulin doses were subsequently adjusted to optimized glycemic control . Glycosylated hemoglobin ( HbA1c ) values , blood glucose , total daily insulin dose , body weight , waist circumference , and the number of hypoglycemic events and adverse events were evaluated . Results At the end of study , the mean reduction in HbA1c between the liraglutide-added group and the insulin-increasing group was not significantly different ( 1.9 % vs. 1.77 % , p>0.05 ) . However , the percentage of subjects reaching the composite endpoint of HbA1c ≤ 7.0 % with no weight gain and no hypoglycemia , was significantly higher in the liraglutide-added group than in the insulin-increasing group ( 67 % vs. 19 % , p<0.001 ) . Add-on liraglutide treatment significantly reduced mean body weight ( 5.62 kg , p<0.01 ) , waist circumference ( 5.70 cm , p<0.01 ) , body mass index ( BMI ) ( 1.93 kg/m2 , p<0.01 ) and daily total insulin dose ( dropped by 66 % ) during 12-week treatment period , while all of these significantly increased with insulin increasing treatment . Add-on liraglutide treated patients had lower rate of hypoglycemic events and greater insulin and oral antidiabetic drugs discontinuation . Gastrointestinal disorders were the most common adverse events in the liraglutide added treatment , but were transient . Conclusions Addition of liraglutide to abdominally obese , insulin-treated patients led to improvement in glycemic control similar to that achieved by increasing insulin dosage , but with a lower daily dose of insulin and fewer hypoglycemic events . Adding liraglutide to insulin also induced a significant reduction in body weight and waist circumference . Liraglutide combined with insulin may be the best treatment option for poorly controlled type 2 diabetes and abdominal obesity Abstract Aims / Introduction : To evaluate the efficacy and safety of the glucagon‐like peptide‐1 receptor agonist , exenatide , in Japanese patients with type 2 diabetes mellitus suboptimally controlled despite therapeutic doses of a sulfonylurea alone or combined with a biguanide or thiazolidinedione . Material s and Methods : Patients were r and omized to a placebo or exenatide , either 5 or 10 μg , given subcutaneously b.i.d . in addition to oral therapy . Patients r and omized to 10 μg exenatide received 5 μg b.i.d . for the first 4 weeks , followed by 10 μg b.i.d . for the last 20 weeks . Results : A total of 179 patients received the study drug and composed the full analysis set ( n = 35 , placebo ; n = 72 , exenatide 5 μg ; n = 72 , exenatide 10 μg ; 68 % male ; 58 ± 10 years ; body mass index 25.5 ± 4.1 kg/m2 ; HbA1c 8.2 ± 0.9 % ; means ± st and ard deviations ) . Baseline to end‐point ( least‐squares means ± st and ard errors ) HbA1c changes ( % ) were −0.28 ± 0.15 ( placebo ) , −1.34 ± 0.11 ( exenatide 5 μg ) and −1.62 ± 0.11 ( exenatide 10 μg ) ( both P < 0.001 , exenatide vs placebo ) . Baseline to end‐point bodyweight changes ( kg ) were −0.47 ± 0.39 ( placebo ) , −0.39 ± 0.28 ( exenatide 5 μg ) and −1.54 ± 0.27 ( exenatide 10 μg ; P = 0.026 , exenatide 10 μg vs placebo ) . Nausea , generally mild to moderate , was reported in 8.6 % ( placebo ) , 25.0 % ( exenatide 5 μg ) and 36.1 % ( exenatide 10 μg ) of patients . Mild to moderate hypoglycemia was reported in 22.9 % ( placebo ) , 51.4 % ( exenatide 5 μg ) and 58.3 % ( exenatide 10 μg ) of patients . Conclusions : Over 24 weeks , exenatide vs the placebo improved glycemic control , reduced bodyweight ( 10 μg ) and was well tolerated in Japanese patients with type 2 diabetes mellitus suboptimally controlled , despite oral therapy including a sulfonylurea . This trial was registered with Clinical Trials.gov ( no. NCT00577824 ) . ( J Diabetes Invest , doi : 10.1111/j.2040‐1124.2010.00084.x , 2011 AIMS The aim of this study was to investigate the vascular effects of liraglutide in patients well controlled on metformin monotherapy . METHODS Forty-four patients with Type 2 diabetes were included in the study . Main inclusion criteria were : pretreatment with metformin on a stable dosage , HbA(1c ) < 53 mmol/mol ( 7.0 % ) , age 30 - 65 years . Patients were r and omized to receive additional liraglutide or to remain on metformin monotherapy . After 6 weeks ( 1.2 mg ) and after 12 weeks ( 1.8 mg ) , venous blood was taken for the measurement of several laboratory markers characterizing vascular and endothelial function . In addition , retinal microvascular endothelial function and arterial stiffness were measured . RESULTS HbA(1c ) levels declined from 45 ± 4 mmol/mol ( 6.3 ± 0.4 % ; mean ± SD ) to 40 ± 3 mmol/mol ( 5.8 ± 0.3 % ) during liraglutide treatment . Asymmetric dimethylarginin was reduced by liraglutide treatment from 0.39 ± 0.08 to 0.35 ± 0.06 μmol/l , E-selectin from 43.6 ± 15.4 to 40.8 ± 15.1 ng/ml , plasminogen activator inhibitor 1 from 861.6 ± 584.3 to 666.1 ± 499.4 ng/ml and intact proinsulin from 9.0 ± 7.2 to 7.0 ± 4.8 pmol/l at 12 weeks of treatment . The microvascular response to flicker light increased from 7.0 ± 15.1 to 15.4 ± 11.5 % after 6 weeks and to 11.1 ± 9.9 % after 12 weeks . No change could be observed for high-sensitivity C-reactive protein , monocyte chemotactic protein 1 , vascular cell adhesion molecule or arterial stiffness parameters . CONCLUSIONS In patients with Type 2 diabetes , well controlled with metformin monotherapy , addition of liraglutide improves several cardiovascular risk markers beyond glycaemic control OBJECTIVE This study assessed the efficacy and safety of once-weekly taspoglutide in patients with type 2 diabetes mellitus inadequately controlled with metformin plus pioglitazone compared with placebo . DESIGN In this r and omized , double-blind , parallel-group , placebo-controlled trial ( T-emerge 3 ) , 326 patients were r and omized to once-weekly sc injections of taspoglutide 10 mg , taspoglutide 20 mg ( 10 mg for first 4 wk ) , or placebo . The primary endpoint was change from baseline in glycosylated hemoglobin ( HbA1c ) at 24 wk . RESULTS A significant reduction in HbA1c was observed with taspoglutide 10 mg and 20 mg vs. placebo ( least square mean -1.35 and -1.40 % vs. -0.45 % , respectively ; P < 0.0001 ) . A greater proportion of taspoglutide-treated patients reached HbA1c target 7 % or less ( 69.8 and 76.1 % vs. 35.1 % ) . With taspoglutide 10 mg and 20 mg vs. placebo , significantly greater reductions in fasting plasma glucose [ -1.87 mmol/liter ( -34 mg/dl ) and -2.12 mmol/liter ( -38 mg/dl ) vs. -0.57 mmol/liter ( -10 mg/dl ) ; P < 0.0001 ] , improvements in homeostasis model assessment of β-cell function score ( 20.65 and 33.52 vs. -2.03 ; P < 0.0001 ) , and significant weight loss ( -0.64 kg and -1.04 kg vs. 0.59 kg ; P < 0.01 ) were observed . Adverse events were generally mild to moderate ; the most frequent adverse events with taspoglutide 10 mg , taspoglutide 20 mg , and placebo were nausea ( 35 , 44 , and 10 % ) , vomiting ( 21 , 24 , and 2 % ) , and injection site reactions ( 24 , 24 , and 5 % ) . CONCLUSIONS Taspoglutide provided glycemic control with weight loss as add-on therapy to metformin plus pioglitazone for inadequately controlled type 2 diabetes mellitus BACKGROUND Insulin replacement in diabetes often requires pr and ial intervention to reach hemoglobin A₁(c ) ( HbA₁(c ) ) targets . OBJECTIVE To test whether twice-daily exenatide injections reduce HbA₁(c ) levels more than placebo in people receiving insulin glargine . DESIGN Parallel , r and omized , placebo-controlled trial , blocked and stratified by HbA₁(c ) level at site , performed from October 2008 to January 2010 . Participants , investigators , and personnel conducting the study were masked to treatment assignments . ( Clinical Trials.gov registration number : NCT00765817 ) SETTING 59 centers in 5 countries . PATIENTS Adults with type 2 diabetes and an HbA₁(c ) level of 7.1 % to 10.5 % who were receiving insulin glargine alone or in combination with metformin or pioglitazone ( or both agents ) . INTERVENTION Assignment by a central ized , computer-generated , r and om-sequence interactive voice-response system to exenatide , 10 µg twice daily , or placebo for 30 weeks . MEASUREMENTS The primary outcome was change in HbA₁(c ) level . Secondary outcomes included the percentage of participants with HbA₁(c ) values of 7.0 % or less and 6.5 % or less , 7-point self-monitored glucose profiles , body weight , waist circumference , insulin dose , hypoglycemia , and adverse events . RESULTS 112 of 138 exenatide recipients and 101 of 123 placebo recipients completed the study . The HbA₁(c ) level decreased by 1.74 % with exenatide and 1.04 % with placebo ( between-group difference , -0.69 % [ 95 % CI , -0.93 % to -0.46 % ] ; P < 0.001 ) . Weight decreased by 1.8 kg with exenatide and increased by 1.0 kg with placebo ( between-group difference , -2.7 kg [ CI , -3.7 to -1.7 ] ) . Average increases in insulin dosage with exenatide and placebo were 13 U/d and 20 U/d . The estimated rate of minor hypoglycemia was similar between groups . Thirteen exenatide recipients and 1 placebo recipient discontinued the study because of adverse events ( P < 0.010 ) ; rates of nausea ( 41 % vs. 8 % ) , diarrhea ( 18 % vs. 8 % ) , vomiting ( 18 % vs. 4 % ) , headache ( 14 % vs. 4 % ) , and constipation ( 10 % vs. 2 % ) were higher with exenatide than with placebo . LIMITATIONS The study was of short duration . There were slight imbalances between groups at baseline in terms of sex , use of concomitant glucose-lowering medications , and HbA₁(c ) levels , and more exenatide recipients than placebo recipients withdrew because of adverse events . CONCLUSION Adding twice-daily exenatide injections improved glycemic control without increased hypoglycemia or weight gain in participants with uncontrolled type 2 diabetes who were receiving insulin glargine treatment . Adverse events of exenatide included nausea , diarrhea , vomiting , headache , and constipation . PRIMARY FUNDING SOURCE Alliance of Eli Lilly and Company and Amylin Pharmaceuticals BACKGROUND Glucagon-like peptide 1 ( GLP-1 ) has been proposed as a treatment for type 2 diabetes . We have investigated the long-term effects of continuous administration of this peptide hormone in a 6-week pilot study . METHODS 20 patients with type 2 diabetes were alternately assigned continuous subcutaneous infusion of GLP-1 ( n=10 ) or saline ( n=10 ) for 6 weeks . Before ( week 0 ) and at weeks 1 and 6 , they underwent beta-cell function tests ( hyperglycaemic clamps ) , 8 h profiles of plasma glucose , insulin , C-peptide , glucagon , and free fatty acids , and appetite and side-effect ratings on 100 mm visual analogue scales ; at weeks 0 and 6 they also underwent dexascanning , measurement of insulin sensitivity ( hyperinsulinaemic euglycaemic clamps ) , haemoglobin A(1c ) , and fructosamine . The primary endpoints were haemoglobin A(1c ) concentration , 8-h profile of glucose concentration in plasma , and beta-cell function ( defined as the first-phase response to glucose and the maximum insulin secretory capacity of the cell ) . Analyses were per protocol . FINDINGS One patient assigned saline was excluded because no veins were accessible . In the remaining nine patients in that group , no significant changes were observed except an increase in fructosamine concentration ( p=0.0004 ) . In the GLP-1 group , fasting and 8 h mean plasma glucose decreased by 4.3 mmol/L and 5.5 mmol/L ( p<0.0001 ) . Haemoglobin A(1c ) decreased by 1.3 % ( p=0.003 ) and fructosamine fell to normal values ( p=0.0002 ) . Fasting and 8 h mean concentrations of free fatty acids decreased by 30 % and 23 % ( p=0.0005 and 0.01 , respectively ) . Gastric emptying was inhibited , bodyweight decreased by 1.9 kg , and appetite was reduced . Both insulin sensitivity and beta-cell function improved ( p=0.003 and p=0.003 , respectively ) . No important side-effects were seen . INTERPRETATION GLP-1 could be a new treatment for type 2 diabetes , though further investigation of the long-term effects of GLP-1 is needed AIM The effect on body composition of liraglutide , a once-daily human glucagon-like peptide-1 analogue , as monotherapy or added to metformin was examined in patients with type 2 diabetes ( T2D ) . METHODS These were r and omized , double-blind , parallel-group trials of 26 [ Liraglutide Effect and Action in Diabetes-2 ( LEAD-2 ) ] and 52 weeks ( LEAD-3 ) . Patients with T2D , aged 18 - 80 years , body mass index ( BMI ) < or = 40 kg/m(2 ) ( LEAD-2 ) , < or = 45 kg/m(2 ) ( LEAD-3 ) and HbA1c 7.0 - 11.0 % were included . Patients were r and omized to liraglutide 1.8 , 1.2 or 0.6 mg/day , placebo or glimepiride 4 mg/day , all combined with metformin 1.5 - 2 g/day in LEAD-2 and to liraglutide 1.8 , 1.2 or glimepiride 8 mg/day in LEAD-3 . LEAD-2/3 : total lean body tissue , fat tissue and fat percentage were measured . LEAD-2 : adipose tissue area and hepatic steatosis were assessed . RESULTS LEAD-2 : fat percentage with liraglutide 1.2 and 1.8 mg/metformin was significantly reduced vs. glimepiride/metformin ( p < 0.05 ) but not vs. placebo . Visceral and subcutaneous adipose tissue areas were reduced from baseline in all liraglutide/metformin arms . Except with liraglutide 0.6 mg/metformin , reductions were significantly different vs. changes seen with glimepiride ( p < 0.05 ) but not with placebo . Liver-to-spleen attenuation ratio increased with liraglutide 1.8 mg/metformin possibly indicating reduced hepatic steatosis . LEAD-3 : reductions in fat mass and fat percentage with liraglutide monotherapy were significantly different vs. increases with glimepiride ( p < 0.01 ) . CONCLUSION Liraglutide ( monotherapy or added to metformin ) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D AIMS This study compared the efficacy and tolerability of taspoglutide versus pioglitazone in subjects with type 2 diabetes inadequately controlled with sulphonylurea ± metformin . METHODS In this double-blind , double-dummy , parallel-group trial , 760 subjects ( 49 % male , age 56.4 years , diabetes duration 8.8 years , body mass index 32.7 kg/m(2 ) and haemoglobin A1c [ HbA1c ] 8.3 % ) were r and omized ( 1 : 1 : 1 ) to subcutaneous injections of taspoglutide 10 or 20 mg once weekly or oral pioglitazone 45 mg daily . The primary endpoint was change in HbA1c after 24 weeks . RESULTS Mean ( ±s.e . ) HbA1c reductions with taspoglutide 10 ( -1.18 ± 0.08 % ) and 20 mg ( -1.36 ± 0.08 % ) were non-inferior to pioglitazone ( -1.30 ± 0.08 % ) ( p = 0.21 and 0.37 , respectively ) ; mean treatment differences were 0.12 ( 95 % confidence interval : -0.03 , -0.26 ) and -0.06 ( -0.20 , 0.08 ) for taspoglutide 10 and 20 mg versus pioglitazone . Mean ( ±s.e . ) changes in body weight ( kg ) were -0.8 ± 0.3 , -1.0 ± 0.3 and 3.6 ± 0.3 for taspoglutide 10 and 20 mg and pioglitazone , respectively ; 8 , 11 and 1 % of patients achieved ≥5 % weight loss . A higher incidence of adverse events ( AEs ) occurred with taspoglutide , predominantly gastrointestinal disturbances and injection-site reactions , result ing in higher rates of discontinuation versus pioglitazone . No treatment differences in serious AEs were observed . CONCLUSIONS Taspoglutide offered good glycaemic control similar to pioglitazone , while achieving beneficial weight loss rather than weight gain , but was associated with more AEs . Due to the higher than expected discontinuation rates , mainly because of gastrointestinal intolerability , the taspoglutide clinical programme was stopped STUDY OBJECTIVE To evaluate the effects of exenatide on some inflammatory markers and to quantify the effect of exenatide on β-cell function . DESIGN A r and omized , double-blind , placebo-controlled trial . SETTING Seven hospitals in Italy . PATIENTS A total of 174 white treatment-naive adults with type 2 diabetes and a glycated hemoglobin ( HbA(1c ) ) level higher than 7.5 % . INTERVENTION After an open-label run-in period of 8 ± 2 months with metformin , patients were r and omized to take exenatide ( 5 μg twice/day for the first 4 weeks , 10 μg twice/day thereafter ) or a placebo volume equivalent for 12 months . MEASUREMENTS AND MAIN RESULTS Body mass index , HbA(1c ) , fasting plasma glucose , postpr and ial plasma glucose , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index , homeostasis model assessment β-cell function index ( HOMA-β ) , fasting plasma proinsulin ( FPPr ) , proinsulin-to-fasting plasma insulin ratio ( Pr : FPI ratio ) , C-peptide , glucagon , vaspin , chemerin , and resistin were evaluated at baseline , at r and omization , and at 3 , 6 , 9 , and 12 months . Patients also underwent a combined euglycemic , hyperinsulinemic , and hyperglycemic clamp with subsequent arginine stimulation to assess insulin sensitivity and insulin secretion . HbA(1c ) was significantly improved with exenatide plus metformin compared with placebo plus metformin . Exenatide plus metformin was also significantly more effective than placebo plus metformin in increasing HOMA-β C-peptide , and all measures of β-cell function after the euglycemic hyperinsulinemic and hyperglycemic clamp . We observed that exenatide plus metformin also reduced resistin compared with placebo plus metformin . No variations in vaspin and chemerin were noted in group-to-group comparisons . We observed a significant correlation between M value increase , an index of insulin sensitivity , and a decrease in inflammatory parameters in the exenatide plus metformin group . CONCLUSIONS The combination of exenatide plus metformin was more effective than metformin alone in improving glycemic control , β-cell function , and inflammatory parameters Glucagon-like peptide 1 ( GLP-1 ) and analogues are being evaluated as a new therapeutic principle for the treatment of type 2 diabetes . GLP-1 suppresses glucagon secretion , which could lead to disturbances of hypoglycemia counterregulation . This has , however , not been tested . Nine healthy volunteers with normal oral glucose tolerance received infusions of regular insulin ( 1 mU x kg(-1 ) x min(-1 ) ) over 360 min on two occasions in the fasting state . Capillary glucose concentrations were clamped at plateaus of 4.3 , 3.7 , 3.0 , and 2.3 mmol/liter for 90 min each ( stepwise hypoglycemic clamp ) ; on one occasion , GLP-1 ( 1.2 pmol x kg(-1 ) x min(-1 ) ) was administered i.v . ( steady-state concentration , approximately 125 pmol/liter ) ; on the other occasion , NaCl was administered as placebo . Glucagon , cortisol , GH ( immunoassays ) , and catecholamines ( radioenzymatic assay ) were determined , autonomous and neuroglucopenic symptoms were assessed , and cognitive function was tested at each plateau . Insulin secretion rates were estimated by deconvolution ( two-compartment model of C-peptide kinetics ) . At insulin concentrations of approximately 45 mU/liter , glucose infusion rates were similar with and without GLP-1 ( P = 0.26 ) . Only during the euglycemic plateau ( 4.3 mmol/liter ) , GLP-1 suppressed glucagon concentrations ( 4.1 + /- 0.4 vs. 6.5 + /- 0.7 pmol/liter ; P = 0.012 ) ; at all hypoglycemic plateaus , glucagon increased similarly with GLP-1 or placebo , to maximum values greater than 20 pmol/liter ( P = 0.97 ) . The other counterregulatory hormones and autonomic or neuroglucopenic symptom scores increased , and cognitive functions decreased with decreasing glucose concentrations , but there were no significant differences comparing experiments with GLP-1 or placebo , except for a significant reduction of GH responses during hypoglycemia with GLP-1 ( P = 0.04 ) . GLP-1 stimulated insulin secretion only at plasma glucose concentrations of at least 4.3 mmol/liter . In conclusion , the suppression of glucagon by GLP-1 does occur at euglycemia , but not at hypoglycemic plasma glucose concentrations ( < or = 3.7 mmol/liter ) . GLP-1 does not impair overall hypoglycemia counterregulation except for a reduction in GH responses , which is in line with other findings demonstrating pituitary actions of GLP-1 . Below plasma glucose concentrations of 4.3 mmol/liter , the insulinotropic action of GLP-1 is negligible OBJECTIVE Therapies that lower blood glucose and provide weight loss may provide meaningful benefits for obese patients with type 2 diabetes mellitus ( T2DM ) . This study assessed the efficacy of taspoglutide compared with placebo on glycemic control and weight in obese patients with T2DM inadequately controlled with metformin monotherapy . DESIGN AND METHODS In a 24-week , r and omized , double-blind , placebo-controlled , multicenter trial , obese adults with T2DM were r and omized ( 1:1 ) to weekly subcutaneous taspoglutide 20 mg ( 10 mg for first 4 weeks ) ( n = 154 ) or placebo ( n = 151 ) for 24 weeks . Efficacy measures included hemoglobin A1c ( HbA1c ) levels , body weight , percentage of patients achieving HbA1c ≤6.5 and ≤7.0 % , and fasting plasma glucose ( FPG ) . Adverse events ( AEs ) were assessed . RESULTS Mean baseline HbA1c was 7.55 % and mean baseline BMI was 36.7 kg/m(2 ) . HbA1c reductions from baseline were significantly greater with taspoglutide than placebo ( least square mean [ LSMean ] , -0.81 % vs. -0.09 % ; P < 0.0001 ) . Weight loss at week 24 was significantly greater with taspoglutide than placebo ( LSMean , -3.16 vs. -1.85 kg ; P < 0.01 ) . In the taspoglutide and placebo groups , target HbA1c levels ( ≤6.5 % ) were achieved by 49 and 16 % of patients , respectively , while 72 and 36 % achieved HbA1c levels ≤7 % . Decreases in FPG were significantly greater with taspoglutide than placebo ( -23.59 vs. 0.09 mg/dl ; P < 0.0001 ) . Nausea and vomiting were the most common AEs associated with taspoglutide , but tended to be transient and generally mild or moderate . CONCLUSIONS In obese patients with T2DM , once-weekly taspoglutide provided the combined benefits of glycemic control and weight loss |
12,424 | 22,872,146 | : Studies to date suggest there are few clinical differences in outcomes with immediate compared with delayed pushing in the second stage of labor , especially when high- quality studies are pooled .
Effects on maternal and neonatal outcomes remain uncertain | OBJECTIVE : To estimate whether immediate or delayed pushing in the second stage of labor optimizes spontaneous vaginal delivery and other perinatal outcomes . | Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To compare perinatal outcomes among women with epidural anesthesia who were encouraged to push at complete dilatation with those who had a period of rest before pushing began . METHODS After a power analysis to determine appropriate sample size ( based upon an α error rate of .05 % and 80 % power ) , a prospect i ve r and omized trial of 252 women with epidural anesthesia was conducted . Patients were r and omized to a rest period or immediate pushing at complete dilatation . Variables measured included rate of fetal descent , length of time of pushing , the number and type of fetal heart rate decelerations , Apgar scores , arterial cord pH values , perineal injuries , type of delivery , length of second stage , maternal fatigue , and endometritis . RESULTS When a period of rest was used before pushing , we found a longer second stage , decreased pushing time , fewer decelerations , and , in primiparous women , less fatigue compared with control patients . Apgar scores , arterial cord pH values , rates of perineal injury , instrument delivery , and endometritis were similar in both groups . CONCLUSION Delayed pushing was not associated with demonstrable adverse outcome , despite second‐stage length of up to 4.9 hours . In select patients , such delay may be of benefit OBJECTIVE This study was undertaken to determine whether a policy of delayed pushing for nulliparous women with continuous-infusion epidural analgesia reduces the risk of difficult delivery ( cesarean delivery , operative delivery from a midpelvic position , low-pelvic procedures with rotation > 45 degrees ) . STUDY DESIGN In this multicenter , r and omized , controlled trial women in the delayed pushing group ( n = 936 ) were advised to wait > or = 2 hours after full dilatation before commencement of pushing . Women in the early pushing group ( n = 926 ) were advised to commence pushing as soon as they had been r and omly assigned . RESULTS Difficult delivery was reduced with delayed pushing ( relative risk , 0.79 ; 95 % confidence interval , 0.66 - 0.95 ) . The greatest effect was on midpelvic procedures ( relative risk , 0.72 ; 95 % confidence interval , 0.55 - 0.93 ) . Although there was little evidence for an effect on low-pelvic procedures , spontaneous delivery was more frequent among women who practice d delayed pushing ( relative risk , 1.09 ; 95 % confidence interval , 1.00 - 1.18 ) . Abnormal umbilical cord blood pH ( < 7.15 venous value or < 7.10 arterial value ) was more frequent in the delayed pushing group ( relative risk , 2.45 , 95 % confidence interval , 1.35 - 4 . 43 ) . However , scores for a summary indicator , the Neonatal Morbidity Index , were similarly distributed in the 2 groups . CONCLUSION Delayed pushing is an effective strategy to reduce difficult deliveries among nulliparous women OBJECTIVE To determine if waiting for a strong urge to push in nulliparas with continuous low-concentration epidural analgesia shortens the pushing duration in the second stage . METHODS Nulliparas with st and ardized patient-controlled epidural analgesia ( 0.0625 % bupivacaine with fentanyl 2 μg/mL ) were r and omly assigned to pushing immediately upon complete cervical dilatation ( n = 85 ) or waiting for a strong urge to push ( n = 117 ) . Urge to push and patient satisfaction were quantified on 100-mm visual analogue scales . Duration of pushing and total duration of the second stage were analyzed as survival time data . RESULTS Women who delayed pushing and those who pushed immediately were similar with respect to maternal characteristics . Women who delayed pushing had a stronger urge to push ( P < .01 ) and a longer second stage ( P < .05 ) than women who pushed immediately . There was no significant difference in the time spent pushing ( median 57 versus 62 minutes , respectively ) or the median level of patient satisfaction ( 80 mm for both groups ) . There were no significant differences in the overall rates of cesarean delivery ( 6 % versus 12 % , respectively ) , cesarean delivery during the second stage ( 2 % in each group ) , spontaneous vaginal delivery ( 70 % versus 69 % , respectively ) , or neonatal or maternal morbidity . CONCLUSION In nulliparas with continuous low-concentration epidural analgesia , delaying pushing until a strong urge is felt does not reduce the duration of pushing in the second stage of labor Objective To identify the obstetric factors relating to anal sphincter injury at first vaginal delivery by prospect i ve cohort study of primiparous women . Methods We compared the results of a bowel function question naire and anal vector manometry before and 6 weeks after delivery in 184 primiparous women . Postpartum , pudendal nerve conduction latency was measured in all women , and anal endosonography was performed in 81 with altered fecal continence or abnormal physiology . Results Sixteen ( 9 % ) women , none of whom had altered fecal continence , were delivered by cesarean . After vaginal delivery , 42 of 168 ( 25 % ) women had impairment of fecal continence and 76 of 168 ( 45 % ) women had abnormal anal physiology . Instrumental vaginal delivery was associated with an 8.1-fold ( 95 % confidence interval [ CI ] 2.7 , 24.0 ; P < .001 ) risk of anal sphincter injury and a 7.2-fold ( 95 % CI 2.8 , 18.6 ; P < .001 ) risk of symptoms . Duration of the second stage of labor beyond 60 minutes led to a 1.7-fold ( 95 % CI 1.14 , 2.48 ; P ; < .01 ) risk of anal sphincter injury and a 1.6-fold ( 95 % CI 1.03 , 2.6 , P = .01 ) risk of symptoms . Epidural analgesia , used in 58 % of vaginal deliveries , prolonged the second stage of labor ( P = .004 ; odds ratio [ OR ] 7.7 ; 95 % CI 4.0 , 14.7 ) and was associated with increased risk of sphincter injury ( P = .02 ; OR 2.1 ; 95 % CI 1.1 , 4.0 ) and of symptoms ( P = .02 ; OR 2.0 ; 95 % CI 1.1 , 3.7 ) . Conclusion Instrumental delivery and a second stage of labor prolonged by epidural analgesia are the obstetric factors that pose the greatest risk of injury to the anal sphincter mechanism in primiparous vaginal delivery Seventy-six primigravidae with epidural analgesia were r and omly assigned to one of two groups for management in the second stage . In one group the women delayed pushing and in the other they were managed conventionally . The two groups were well matched for maternal and infant characteristics , including position and level of the presenting part at full dilatation and fetal scalp blood pH. The mean waiting time in the second stage before pushing was increased from 27 min in the conventional group to 123 min in the delayed group . This delay was not associated with an increase in abnormal fetal heart rate abnormalities or any decrease in umbilical cord pH or Apgar scores . In contrast , the delay was associated with an increase in spontaneous deliveries and a decrease in forceps deliveries ( P = 0.06 ) . These findings suggest a need for redefining the management of the second stage of labour with epidural analgesia OBJECTIVE To determine if the use of delayed pushing after the onset of the second stage of labor decreases the time of active pushing and decreases maternal fatigue . DESIGN R and omized clinical trial . SETTING Labor and delivery unit of a not-for-profit community hospital . PATIENTS / PARTICIPANTS Convenience sample of nulliparous laboring women with epidural anesthesia . INTERVENTIONS Immediate or delayed pushing ( 2 hours ) during the second stage of labor at the time of complete cervical dilatation . MAIN OUTCOME MEASURES The length of pushing , total length of the second stage , and maternal fatigue . RESULTS A total of 77 women were studied ( immediate pushing group=39 ; delayed pushing=38 ) . The immediate pushing group averaged 94 ( ± 57 ) minutes in active pushing , while the delayed pushing group averaged 68 ( ± 46 ) minutes , a statistically significant difference ( p=.04 ) . No significant differences were found in fatigue scores between the immediate and delayed pushing groups ( p>.05 ) . CONCLUSIONS We found that by delaying the onset of active pushing for 2 hours after the beginning of the second stage of labor , the time that nulliparous women with epidural anesthesia spent in active pushing was significantly decreased by 27 % . Although the delayed pushing group rested for up to 2 hours , the total time in the second stage of labor averaged only 59 minutes longer than the immediate pushing group OBJECTIVE To compare outcomes between women receiving epidural anesthesia assigned to a group following either a 1-hour " delayed " pushing protocol or directed to initiate pushing at full cervical dilation . STUDY DESIGN Using a r and omized , controlled design , multivariate analyses were used to evaluate second stage labor duration and Apgar scores . An estimated odds ratio equation evaluated fetal descent progress . RESULTS A 13.68-minute difference occurred in second stage labor length ( p = 0.225 ) . No differences were found in Apgar scores ( p > 0.09 ) . An estimated odds ratio , that progress in terms of one fetal station unit would occur for control group subjects as compared with subjects with similar progress in the experimental group , was 1.51 ( 95 % confidence interval : 1.16 , 1.95 ) . CONCLUSION Second stage labor was not significantly lengthened , and a similar rate of fetal descent occurred in the absence of directed pushing . Findings support further research on the potential advantages of minimizing the duration of pushing in labor Objective To assess the effects of delayed vs immediate pushing in second stage of labour with epidural analgesia on delivery outcome , postpartum faecal continence and postpartum anal sphincter and pudendal nerve function Background Although there are two methods of caring for women with epidural anesthesia during second-stage labor ( coached closed-glottis pushing immediately at 10-cm cervical dilation or delayed pushing until the woman feels the urge to push , passive fetal descent , and encouragement of open-glottis pushing when the woman has the urge to push ) , there are limited data concerning which method is most optimal for fetal well-being . Objective To evaluate effects on fetal well-being , as measured by fetal oxygen saturation , of two different methods of second-stage labor nursing care for women with epidural anesthesia . Methods Forty-five nulliparous women who had progressed to the second stage were r and omized to 1 of 2 groups ( immediate or delayed pushing ) . Fetal oxygen saturation was continuously monitored and values at 10 cm , initiation of pushing and immediately prior to birth , as well as the amount of time that fetal oxygen saturation values were abnormal ( ≤30 % ) were compared between groups . Also evaluated were additional measures of fetal well-being such as fetal heart rate patterns , Apgar scores , and umbilical cord blood gases and maternal outcomes including length of labor , method of birth , and perineal status . Results There was a significant difference between groups in fetal oxygen desaturation during the second stage ( immediate : M = 12.5 ; delayed : M = 4.6 ) F(1 , 43 ) = 12.24 , p = .001 , and in the number of ≥2-min epochs of fetal oxygen saturation < 30 % ( immediate : M = 7.9 ; delayed : M = 2.7 ) , F(1 , 43 ) = 6.23 , p = .02 . There were more variable decelerations of the fetal heart rate in the immediate pushing group ( immediate : M = 22.4 ; delayed : M = 15.6 ) F(1 , 43 ) = 5.92 , p = .02 . There were no differences in length of labor , method of birth , Apgar scores , or umbilical cord blood gases . Women who pushed immediately had more perineal lacerations ( immediate : n = 13 ; delayed : n = 5 ) χ2(1 , N = 45 ) = 6.54 , p = .01 . Discussion Delayed pushing results in less fetal oxygen desaturation and less ≥2-min epochs of fetal oxygen saturation < 30 % during second-stage labor than the immediate pushing method ; thus , delayed pushing is more favorable for fetal well-being as measured by fetal oxygen saturation OBJECTIVES This study was undertaken to examine the national and regional rates of operative delivery among almost one quarter million births in a single year in the nation 's largest healthcare delivery system , using variation as an arbiter of the quality of decision making . STUDY DESIGN We compared the variation in rates of primary cesarean and operative vaginal delivery in facilities of the Hospital Corporation of America during the year 2004 . RESULTS In 124 facilities representing almost 220,000 births during a 1-year period , the primary cesarean and operative vaginal delivery rates were 19 % + /- 5 % ( range 9 - 37 ) and 7 % + /- 4 % ( range 1 - 23 ) . Within individual geographic regions , we consistently found variations of 200 - 300 % in rates of primary cesarean delivery and variations approximating an order of magnitude for operative vaginal delivery . CONCLUSION Within broad upper and lower limits , rates of operative delivery in the United States are highly variable and suggest a pattern of almost r and om decision making . This reflects a lack of sufficient reliable , outcomes -based data to guide clinical decision making Objective To test the hypothesis that a policy of delaying active pushing in nulliparous women with epidural analgesia in labour reduces operative vaginal deliveries Purpose : Comparison of two different methods for management of second stage of labor : immediate pushing at complete cervical dilation of 10 cm and delayed pushing 90 minutes after complete cervical dilation . Study Design and Methods : This study was a r and omized clinical trial in a labor and delivery unit of a not-for-profit community hospital . A sample of 44 nulliparous mothers with continuous epidural anesthesia were studied after r and om assignment to treatment groups . Subjects were managed with either immediate or delayed pushing during the second stage of labor at the time cervical dilation was complete . The primary outcome measure was the length of pushing during second stage of labor . Secondary outcomes included length of second stage of labor , maternal fatigue and perineal injuries , and fetal heart rate decelerations . Two-tailed , unpaired Student 's t-tests and Chi-square analysis were used for data analysis . Level of significance was set at p < .01 following a Bonferroni correction for multiple t-tests . Results : A total of 44 subjects received the study intervention ( N = 28 immediate pushing ; N = 16 delayed pushing ) . The delayed pushing group had significantly shorter amount of time spent in pushing compared with the immediate pushing group ( 38.9 ± 6.9 vs. 78.7 ± 7.9 minutes , respectively , p = .002 ) . Maternal fatigue scores , perineal injuries , and fetal heart rate decelerations were similar for both groups . Clinical Implication s : Delaying pushing for up to 90 minutes after complete cervical dilation result ed in a significant decrease in the time mothers spent pushing without a significant increase in total time in second stage of labor . In clinical practice , healthcare providers sometimes resist delaying the onset of pushing after second stage of labor has begun because of a belief it will increase labor time . This study 's finding of a 51 % reduction in pushing time when mothers delay pushing for up to 90 minutes , with no significant increase in overall time for second stage of labor , disputes that concern |
12,425 | 19,821,428 | AUTHORS ' CONCLUSIONS In the absence of evidence of efficacy , at present , for oral nabumetone in acute postoperative pain , its use in this indication is not justified . | BACKGROUND Nabumetone is a non-steroidal anti-inflammatory drug ( NSAID ) used mainly in treating pain associated with arthritis .
The usual oral dose for osteoarthritis is 1000 mg daily , and higher doses are not advised in older patients .
There are no known systematic review s of its analgesic efficacy in acute postoperative pain .
This review sought to evaluate the efficacy and safety of oral nabumetone in acute postoperative pain , using clinical studies of patients with established pain , and with outcomes measured primarily over 6 hours using st and ard methods .
This type of study has been used for many decades to establish whether drugs have analgesic properties .
OBJECTIVES To assess the efficacy of single dose oral nabumetone in acute postoperative pain , and any associated adverse events . | Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale |
12,426 | 17,054,282 | Mild ' to ' moderate ' tooth sensitivity and gingival irritation were the most common side effects .
The whitening strips and products with high concentrations of HP caused more users to complain from tooth sensitivity .
There is evidence that whitening products work when compared with placebo/no treatment .
There are differences in efficacy between the products , mainly due to the levels of active ingredients , hydrogen peroxide and carbamide peroxide . | BACKGROUND During the last decade tooth whitening products have become widely available in the USA for sale over-the-counter or dispensed by dentists for use at home .
With the current rapid growth in dem and for tooth whitening it is imperative that the dental community base its recommendations to patients on sound scientific evaluations conducted in well- design ed and independent studies .
OBJECTIVES To evaluate the effectiveness ( versus a placebo or another active product ) and side effects of over-the-counter or dentist-dispensed chemically-based tooth whitening products design ed for home use . | The conservative technique of professionally dispensed and supervised , home-administered vital bleaching is now a routine treatment in the dental profession . This double-blind study evaluated the Rembr and t Lightening Gel and Whitening Toothpaste for shade change , colorimeter shade change . As well , it evaluated soft tissue health by periodontal probing , plaque index , and bleeding index . A patient question naire evaluated perception of whitening , perception of oral hygiene , average hours per day , and average days per week . Bleaching trays were worn over a 4-week period . The bleaching system showed definitive whitening effects as evaluated with the Vita shade guide and the colorimeter . The bleaching system had no deleterious effects on the soft tissue . The Rembr and t toothpaste alone demonstrated two-shade lightening . This vital bleaching system shows definitive whitening of the teeth in short periods of time with no adverse effects To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results PURPOSE To compare the clinical response of two self-directed vital bleaching systems under market use conditions . MATERIAL S AND METHODS A r and omized , parallel-group clinical trial was conducted . A total of 20 healthy adults were r and omized to either a 6.0 % hydrogen peroxide strip-based bleaching system or a combination system involving a 10 % carbamide peroxide gel in a stock tray along with an anticavity whitening dentifrice and after-bleaching whitening mouthrinse . Only the maxillary arch was bleached over a 14-day period . Subjects were evaluated at 3 , 8 and 15 days . Efficacy was measured objective ly using digital image analysis to derive individual color parameters ( L*a*b * ) and overall color change ( deltaE * ) . RESULTS After 14 days , the adjusted mean reduction in yellow ( Ab * ) was -2.23 + /- 0.157 for the whitening strips compared to -0.97 + /- 0.188 for the combination system . This represented a highly statistically significant ( P < 0.0001 ) , two-fold superior reduction in yellowness for the whitening strip group compared to the marketed control . Similar results were seen for other color parameters , with the whitening strip group exhibiting two-fold color improvement relative to the tray/dentifrice/rinse combination . With respect to tolerability , tooth sensitivity and oral irritation were the most common findings . Considering event duration and severity , median bleaching tolerability severity-days scores were 0.07 and 0.58 for the strip and combination systems respectively , with these treatments differing statistically ( P= 0.04 1 ) favoring the whitening strips A r and omized , parallel , examiner-blind clinical trial was conducted to compare two professionally dispensed vital bleaching systems . A total of 20 subjects were r and omized to either the Crest Professional Whitestrips system or the Nite White Excel 2 tray system , balancing for baseline tooth color . During the 2-week treatment period , subjects were instructed to use the strip system for one-half hour twice daily ( 14 contact hours ) and the tray system for 2 hours daily ( 28 contact hours ) . Only the maxillary teeth were treated , and all bleaching was unsupervised . Whitening was measured objective ly by comparing digital images of the maxillary anterior dentition at pretreatment and posttreatment . Compared with baseline , both the strip and tray systems exhibited statistically significant decreases ( P < 0.05 ) in yellowness ( delta b * ) and increases in brightness ( delta L * ) . Compared with the tray-system group , the strip-system group experienced significant additional whitening ( P < 0.03 ) , as evidence d by a 62 % to 209 % improvement in tooth color ( delta b * , delta L * , and delta E * ) after 14 days . Both systems were generally well tolerated , and none of the subjects discontinued treatment early because of an adverse event . Under the conditions tested , this clinical trial demonstrates that the 14-contact-hour treatment with the strip system result ed in superior whitening efficacy compared with the 28-contact-hour treatment with the tray system This clinical study compared the efficacy of three different bleaching techniques with respect to the bleaching times required in order to achieve six grade s of whitening in human teeth . Any side effects that were noted and the patients ' acceptance of the method were recorded by a visual analog scale ranging from 0 to 10 . Moreover , epoxy casts from the study teeth were analyzed by scanning electron microscopy in order to detect any potential changes in the enamel surface due to treatments . Thirty-nine volunteers participated in the study and were allocated r and omly to one of three different bleaching treatments : Group A ( n=13 ) used Whitestrips ( over-the-counter technique ; one cycle=30 minutes ) , Group B ( n=13 ) used Opalescence PF 10 % ( at-home bleaching technique ; one cycle=8 hours ) and Group C ( n=13 ) used Opalescence Xtra Boost ( in-office bleaching technique ; one cycle=15 minutes ) until a defined whitening of six tabs compared to the baseline were reached ( assessed by the VITA shade guide ) . All three methods achieved six grade s of whitening . The mean treatment time required to reach the defined level of whitening was 31.85 + /- 6.63 cycles in Group A , 7.15 + /- 1.86 cycles in Group B and 3.15 + /- 0.55 cycles in Group C. All products differed significantly from each other in terms of treatment cycles and required treatment time ( p<0.001 by ANOVA and Mann-Whitney-U-test ) . Using the VA scale , side effects noted within the three groups were minimal . Tooth hypersensitivity ranged from 2.62 ( Whitestrips ) to 3.38 ( Opalescence PF ) , and gingival irritation ranged between 0.23 ( Opalescence Xtra Boost ) and 0.85 ( Whitestrips ) . The most accepted method was the at-home bleaching technique . None of the teeth studied showed detectable enamel surface changes in the subsequent SEM analysis using 200x and 2000x magnification This study tested the hypothesis that beveling and /or etching enamel does not affect the 6-month clinical performance of the self-etch adhesive Clearfil SE Bond in class V noncarious lesions . With Institutional Review Board approval , 34 patients were enrolled in this study . A total of 120 noncarious cervical lesions were selected and assigned to 4 groups : ( 1 ) Clearfil SE Bond was applied without any cavity preparation ; ( 2 ) After the enamel was beveled , Clearfil SE Bond was applied ; ( 3 ) After the enamel was etched for 15 seconds with 35 % phosphoric acid , Clearfil SE Bond was applied ; ( 4 ) After the enamel was beveled and etched with 35 % phosphoric acid for 15 seconds , Clearfil SE Bond was applied . A microfilled composite resin was used for all restorations . Six months after initial placement , 120 restorations ( a 100 % recall rate ) were re-evaluated . Retention rates at 6 months were 100 % for all groups . Sensitivity to air improved from baseline to 6 months , but the overall difference was not statistically significant . The 6-month retention rate of the self etch dentin adhesive system Clearfil SE Bond was not improved by enamel beveling or by enamel etching . For the self-etch material Clearfil SE Bond , instrumentation or etching of enamel may not be critical for its clinical performance at 6 months A r and omized and controlled , parallel-group clinical trial compared the whitening benefits of a novel 5.3 % hydrogen peroxide bleaching strip to 10 % , 15 % , and 20 % carbamide peroxide tray-based bleaching systems . A total of 36 healthy adults were r and omized to a 14-day regimen in which both arches were whitened for 1 hour per day in the whitening-strip group or 2 hours per day in the tray groups . Efficacy was measured objective ly using digital images of the anterior teeth at baseline and after 14 days of treatment . Overall tooth color ( L*a*b * ) was derived from individual pixel values , and then mean levels of delta b * , delta L * , and composite color ( delta E * ) were compared using analysis of covariance . After 14 days of treatment , all groups experienced a greater than 1-unit mean improvement in delta b * , delta L * , and delta E * relative to baseline . For the primary study variable , reduction of yellow ( delta b * ) outcomes after 14 hours of using the experimental strip were comparable to those observed with the 10 % tray group after 28 hours of use . These two treatment groups did not differ statistically with respect to any of the color measurements used in this study . For the tray groups , there was a reasonable dose relationship for the primary end point , delta b * , with the 15 % and 20 % tray groups averaging 17 % and 68 % improvements in yellow , respectively , over the 10 % group . Except for the 20 % carbamide peroxide system , where sensitivity was relatively common , all test products were well tolerated . In this first comparative evaluation vs marketed controls , use of the whitening strips twice daily for 14 days yielded a highly significant improvement in tooth color vs baseline This clinical trial tested the efficacy and safety of a professional strip-based whitening system ( Crest Whitestrips Supreme ) using the manufacturer 's recommended 3-week treatment regimen . These strips have a higher concentration , but a similar amount of hydrogen peroxide relative to Crest Professional Whitestrips , because the thickness of the gel on strips is reduced . Tooth whitening was measured using the value-oriented VITA Classic Shade Guide before and after treatment . Twenty-nine subjects were treated with either Crest Whitestrips Supreme or placebo strips that did not contain hydrogen peroxide . Participants in the experimental group achieved a mean lightening of nearly eight VITA shades relative to placebo , with minimal side effects A 2-week study was conducted to compare the tooth-whitening efficacy of two 10 % carbamide peroxide products : Colgate Platinum Professional Toothwhitening System and Rembr and t Lighten Bleaching Gel . Fifty subjects were divided into two groups and assigned a product to use for 2 weeks . Change in tooth color was measured by reflectance spectroscopy at the initiation of study , at 1 week , and at 2 weeks into the study . Color change was calculated using the color-difference equation established by the Commission International de L'Eclairage . Results showed that Colgate Platinum was 62 % more effective at tooth whitening after 1 week and 83 % more effective after 2 weeks of treatment vs Rembr and t. At the termination of the study , the mean color difference ( deltaE ) for Colgate Platinum was 4.29 and 2.34 for Rembr and t. Statistical analysis demonstrated that the Colgate product is significantly superior at increasing tooth whiteness , increasing tooth lightness , reducing redness , and reducing yellowness . In this study , no adverse reactions were noted on clinical examination and none were reported by panelists with normal healthy dentition PURPOSE To evaluate objective and subjective whitening responses of two marketed vital bleaching systems under intended use conditions . MATERIAL SA ND METHODS : The r and omized clinical trial evaluated 50 adults who received either a combination system with a 3 % hydrogen peroxide bleaching gel , pre-formed dual arch tray , dentifrice and oral rinse ( Rapid White ) , or 6 % hydrogen peroxide whitening strips ( Crest Whitestrips ) . Efficacy was assessed objective ly from L*a*b * tooth color at Days 7 & 14 , while subjective , first-person whitening perception was measured by question naire . A cumulative multinomial probability model was generated to predict subjective responses from objective ly measured tooth color . RESULTS At end-of-treatment , adjusted mean deltab * was -2.05 + /- 0.158 for the whitening strip group compared to -0.69 + /- 0.141 for the combination group , with these groups differing significantly ( P < 0.0001 ) . This response held across every color parameter and time point in this study . Relative to the combination system , subjects in the whitening strip group rated that product significantly ( P < 0.01 ) more favorably with respect to the amount of whiteness improvement , as well as whitening satisfaction and overall impression . These subjective responses were correlated with objective changes in tooth color measured during treatment . When the deltab * effect was included in a cumulative multinomial probability model , deltaL * , deltaa * , and treatment were non-significant predictors . Odds ratios demonstrate that a subject had 3.3 times ( 1/0.3003 = 3.33 ) greater odds of selecting a higher whiteness rating when the value of deltab * was decreased by 1.0 unit ( less yellowness ) . Similar results were noted for whitening satisfaction and overall impression of treatment PURPOSE The purpose of this study was to evaluate the 2-year effectiveness of a carbamide peroxide at-home bleaching gel used to provide tooth lightening treatment . MATERIAL AND METHODS Twenty-nine patients participated in the original study , during which they treated their maxillary teeth with a 10 % carbamide peroxide gel nightly for 2 weeks . Shades were determined before and after treatment by comparison with a Vita shade guide . Twenty-four patients ( a recall rate of 83 % ) were recalled for evaluation 2 years after the initial bleaching treatment . The shade of the maxillary incisors was evaluated and compared with shades before , immediately after , and at 6 months and 2 years after initial treatment . Data were analyzed using a repeated- measures analysis of variance . RESULTS At 2 years after bleaching with a 10 % carbamide peroxide gel , the median shade was D2 , a six-increment difference from the baseline median of D3 . Twenty of 24 patients ( 83.3 % ) had a shade change of two or more units , which is the threshold value for bleaching efficacy using American Dental Association guidelines . The lightening result remained statistically significant ( p < .0001 ) at 2 years . CLINICAL SIGNIFICANCE Although some reversal of the lightening effect occurs over time following the original bleaching treatment , loss of the lighter color appears to be gradual for most patients . Although the longevity of the lightening effect remains to be determined , this clinical trial indicates that the majority of patients have a satisfactory result 2 years after treatment NUPRO Gold Tooth Whitening System was evaluated for efficacy according to the proposed ADA guidelines for acceptance . Sixty participants with discolored anterior teeth participated in a 14-day , double-blind , clinical trial . The participants were matched for age , gender , and oral health status and were given either a placebo gel without the active agent or the NUPRO Gold active gel , which they wore in a custom-fabricated mouth guard for home use . The shade of each participant 's maxillary anterior teeth was evaluated using a value-oriented Vita Lumin Vacuum Shade Guide before the study . The same shade guide was used to determine shade changes . Time of use of the agent and potential side effects , such as tooth and gingival hypersensitivity and tissue irritation , were assessed at all recall examinations and were recorded by participants in daily diaries . The average shade change for the placebo users was less than one shade . The average shade change for the NUPRO Gold users was 6.96 shades . Tooth hypersensitivity varied from none to severe . Tissue irritation was minimal . The results of these evaluations indicate that NUPRO Gold is effective as a tooth-whitening system , when administered properly under the supervision of a dentist , with commonly reported side effects of transient tooth sensitivity and minimal gingival sensitivity . Little or no change in tissue health was noted . This study was supported by Dentsply Preventive Care ( York , Pennsylvania ) The methods used to lighten tooth discolouration while conserving the tooth structure have attracted much attention in a society which places a high value on esthetics . The purpose of this article is to present a home bleaching agent that uses a film-forming preparation containing carbamide peroxide ( CP ) which , while degrading , serves as a slow release delivery system of the bleaching agent . The efficacy of the preparation containing 3 % CP and 10 % CP on reduction of tooth discolouration is evaluated by a Chromameter in a double-blind placebo-controlled study . The effect of the tested bleaching agent on the gingival status , plaque accumulation and pulp sensitivity is also assessed The IntelliClean System from Sonicare and Crest combines a rechargeable sonic power toothbrush and a novel liquid toothpaste into one integrated system , providing the opportunity to re-dose with toothpaste during the brushing cycle . The purpose of this study was to investigate cleaning effects from in-mouth re-dosing with toothpaste during the brushing cycle vs conventional bolus dosing . This was a r and omized , examiner-blind , six-period , crossover clinical study . Eighteen adult subjects used an experimental integrated system employing either a re-dosing regimen ( 2 doses at the start of brushing with 1 additional in-mouth dose during the last 30 seconds of brushing [ 2 + 1 ] ) or a conventional regimen ( 2 doses at the start of brushing only [ 2 + 0 ] ) . Gingival crevicular fluid ( GCF ) was sample d at the final brushing quadrant from a preselected site in the gingival sulcus using filter strips at baseline and at 4 , 15 , and 120 minutes postbrushing . Mean change from baseline in the concentrations of total facultative anaerobes ( TFAs ) and gram-negative anaerobes ( GNAs ) in the GCF at 120 minutes posttreatment were modeled separately using general linear mixed models . Area under the curve of surfactant ( sodium dodecyl sulfate [ SDS ] ) in GCF over 2 hours postbrushing was calculated and modeled using an analysis of variance model . All hypotheses were tested 2-sided at the 5 % significance level . Relative to the conventional regimen , the re-dosing ( 2 + 1 ) regimen produced a significantly greater reduction in log10 ( TFA colony-forming units [CFU]/microL GCF ) after brushing , 0.99+/-0.12 vs 0.65+/-0.12 ( mean change + /- st and ard error ) , and a significantly greater reduction in log10 ( GNA CFU/microL GCF ) after brushing , 0.75 + /-0.14 vs 0.45 + /- 0.14 . The re-dosing regimen led to significantly more SDS in GCF relative to the conventional regimen over the 2-hour time period . Re-dosing of liquid toothpaste during the brushing cycle with the IntelliClean System leads to a significantly increased cleaning effect , as defined by a reduced bacterial count in GCF , and significantly higher levels of surfactant in the GCF up to 2 hours after the brushing event PURPOSE A r and omized , double blind clinical trial was conducted to evaluate initial color improvement and post-treatment color retention following vital bleaching with a strip-based tooth whitening system . MATERIAL S AND METHODS After balancing for baseline color , 57 healthy adults were r and omized to either whitening strips with a 5.3 % hydrogen peroxide bleaching gel ( Crest Whitestrips ) or placebo strips without hydrogen peroxide . Maxillary and m and ibular anterior teeth were treated twice daily for 30 minutes each over a 2-week period , and efficacy was measured objective ly by comparing digital images of teeth collected at baseline , end-of-treatment ( Week 2 ) and 6 months after treatment ( Month 6 ) . RESULTS The whitening strip group experienced a highly significant ( P < 0.0001 ) reduction in yellow of -2.0 deltab * units versus baseline and -1.95 deltab * units versus placebo , with similar results noted for the other color parameters in the study . Most of the initial color change remained at 6 months post-treatment , with the whitening strip group continuing to demonstrate highly significant ( P < 0.0001 ) improvements in tooth color relative to baseline and placebo . Age was found to significantly contribute to initial color improvement , with younger subjects experiencing a greater initial reduction in yellowness compared to older participants , but not to post-treatment color retention . The whitening strips were well tolerated , with minor tooth sensitivity and oral irritation representing the most common findings during treatment . There were no persistent or new treatment-related adverse events during the 6-month monitoring period OBJECTIVE This in vitro study compared the shade changes in extracted teeth during 2 weeks ' whitening with 5 % , 10 % , or 16 % carbamide peroxide . METHOD AND MATERIAL S After color calibration , the sole examiner selected 110 extracted unrestored , noncarious teeth , shade A3 or darker on a value-oriented guide . The teeth were r and omly distributed into equal color groups . The control group ( 11 teeth ) was treated with 0.9 % saline , while the experimental groups ( 33 teeth each ) were treated with 5 % , 10 % , or 16 % carbamide peroxide . The solutions remained on the teeth for 8 hours . The teeth and tray were rinsed with tap water for 2 minutes , then rehydrated in 0.9 % saline for 16 hours in the humidifier . The shade was assessed , and the process was repeated daily for 2 weeks . RESULTS Repeated- measures analysis of variance indicated a significant difference in overall shade values between the control and all carbamide peroxide-treated groups at days 8 and 15 . A Kaplan-Meier Survival Analysis indicated a quicker two-tab color change for the 10 % and 16 % groups than the 5 % group . However , continuation of the 5 % treatment to 3 weeks result ed in shades that approached the 2-week 10 % and 16 % values . CONCLUSION Lower concentrations of carbamide peroxide take longer to whitening teeth but eventually achieve the same result as higher concentrations . Higher concentrations may cause increased sensitivity OBJECTIVE The objective of this r and omized , double-blind , parallel-group clinical study was to compare the tooth whitening efficacy of two tooth whitening gel products -- Colgate Simply White Night Clear Whitening Gel containing either 25 % carbamide peroxide , or 8.7 % hydrogen peroxide -- when used once daily at night . METHODOLOGY Following a baseline tooth shade evaluation using the Vita Shade Guide , qualifying adult male and female subjects from the Central New Jersey area were r and omized into two treatment groups , which were balanced for baseline Vita Shade Guide scores , gender and age . The treatment groups were : 1 ) a tooth whitening gel containing 25 % carbamide peroxide ; or 2 ) a tooth whitening gel containing 8.7 % hydrogen peroxide . All subjects were given a commercially available , non-whitening dentifrice and a soft-bristled toothbrush at the beginning of the study . In addition , they were also given one of the two tooth whitening gel products . All subjects were instructed to brush their teeth for one minute twice daily ( morning and evening ) with the non-whitening toothpaste . The subjects were further instructed to apply their assigned tooth whitening gel product once daily at night , per the instructions provided . Evaluations of tooth shade for each subject were repeated after two weeks , and again after three weeks of product use . RESULTS Fifty-nine ( 59 ) subjects complied with the protocol and completed the three-week study . At both the two-week and three-week examinations , all subjects exhibited statistically significant ( p < 0.05 ) tooth shade lightening relative to baseline tooth shade . Further , there was no statistically significant difference in tooth shade lightening between the two tooth whitening gel products . CONCLUSION The results of this clinical study indicate that after once daily use at night for two or three weeks , a tooth whitening gel containing 25 % carbamide peroxide and a tooth whitening gel containing 8.7 % hydrogen peroxide both provided statistically significant tooth shade lightening relative to baseline tooth shade . The results also showed that there was no statistical difference in tooth whitening efficacy between the two tooth whitening gel products This clinical trial compared the effects of hydrogen peroxide concentration and toothbrushing on clinical response to vital bleaching . Tooth bleaching was accomplished with a flexible , polyethylene strip coated with a hydrogen peroxide bleaching gel worn for 30 minutes twice daily over a 14-day period . A total of 36 subjects were r and omized to 1 of 3 treatment groups : 5.3 % hydrogen peroxide strip plus prebrushing , 6.5 % hydrogen peroxide strip plus prebrushing , or 6.5 % hydrogen peroxide strip without prebrushing . Two groups brushed with regular anticavity toothpaste immediately before bleaching , while the other group performed ad libitum brushing only . Tooth color was measured over a 14-day period using digital images of the anterior dentition . Over the 14-day treatment period , all 3 strip groups experienced highly significant ( P < 0.001 ) whitening as evidence d by decreased yellowness ( delta b * ) and increased brightness ( delta L * ) , as well as composite color change ( delta E * ) relative to baseline . Keeping brushing constant , the 6.5 % hydrogen peroxide strip plus prebrushing group experienced a 31 % to 60 % improvement in whitening relative to the 5.3 % hydrogen peroxide st and ard . Keeping concentration constant at 6.5 % hydrogen peroxide , the prebrushing group experienced a directional 5 % to 33 % improvement in whitening relative to no prebrushing . All treatments were generally well tolerated . This study demonstrates that for strip-based delivery , increasing hydrogen peroxide concentration to 6.5 % results in a significant improvement in efficacy with few tolerability trade-offs BACKGROUND Agents with carbamide peroxide , or CP , in various concentrations are widely prescribed for at-home tooth whitening . It is not clear , however , if the more concentrated gels will whitening teeth to a greater extent , as no controlled clinical trials have been reported . The authors conducted a double-blind study of human subjects to evaluate whether a 15 percent CP tooth-whitening system was more effective than a 10 percent CP system , and to determine if tooth sensitivity increased with use of the higher concentration . METHODS The authors recruited 57 subjects with maxillary anterior teeth of shade A3 or darker ( as gauged against a value-oriented shade guide ) . The subjects were 18 to 65 years of age and in good general and dental health . After matching the subjects by sex and age , the authors r and omly assigned them to either a control group , which used a 10 percent CP whitening agent , or an experimental group , which used a 15 percent CP agent . RESULTS The results indicated that there was no significant difference in shade change between the groups after one week of treatment ( t = 1.455 , P = .05 ) , but there was a significant difference at the end of the treatment period ( t = 2.303 , P < .05 ) , as well as two weeks after treatment concluded ( t = 2.248 , P < .05 ) . There was no significant difference in sensitivity ( t = 1.399 , P > .05 ) . CONCLUSIONS There was a significant difference in color change between the 10 percent CP and 15 percent CP groups at the end of the study period . There was no significant difference in level of tooth sensitivity between the two groups , and the incidence was equal ; there was , however , a significant difference in variability of tooth sensitivity between the two groups . CLINICAL IMPLICATION S If performed under the careful guidance of a dentist , at-home whitening is an effective treatment , regardless of whether 10 percent CP or 15 percent CP is used . There may be added color change and varying sensitivity with the use of 15 percent CP BACKGROUND Use of higher peroxide concentrations for professional at-home vital bleaching often balances two factors in patient compliance : whitening and tolerability . Development of a polyethylene strip coated with a very thin ( 0.10-millimeter ) layer of 14 percent hydrogen peroxide gel ( Crest Whitestrips Supreme , Procter & Gamble , Cincinnati)--which represents an increase in concentration and a decrease in amount of gel -- was believed to allow for greater at-home whitening with little additional oral soft-tissue exposure to peroxide . METHODS The authors conducted a r and omized , double-blind , two-week clinical trial with 38 adults to evaluate the safety and efficacy of twice-daily use of the thin , concentrated bleaching gel strip versus the effects of a control product ( Crest Whitestrips , Procter & Gamble ) . The two products differed only in concentration ( 14 percent versus 6 percent ) and gel layer thickness ( 0.10 mm versus 0.20 mm ) . The authors measured efficacy from digital images using the Commission Internationale de l'Eclairage L*a*b * color scale . They assessed safety via subject interviews and clinical examination and compared treatments using analysis of covariance . RESULTS Relative to baseline color , both strip groups exhibited significant ( P < .001 ) improvement in yellowness , brightness and composite color change . Between-group comparisons after two weeks demonstrated significant ( P < .003 ) color improvement for the experimental strip relative to the control . Both products were well-tolerated generally . Despite the concentration differences , clinical examination of each group showed a similar low level ( 11 percent ) of " minor oral irritation . " CONCLUSION Use of the thin 14 percent hydrogen peroxide gel strip result ed in greater whitening , including 42 to 49 percent greater improvement in tooth color and faster whitening onset than that seen with a 6 percent hydrogen peroxide whitening strip , without clinical evidence of increased oral-tissue irritation . CLINICAL IMPLICATION S Use of whitening strips with a thin , concentrated layer of hydrogen peroxide gel may represent a useful approach for professionally directed at-home vital bleaching PURPOSE To evaluate in a r and omized , double-blind , placebo-controlled clinical trial the initial , cumulative and sustained whitening with a brush-applied , peroxide-based , overnight tooth whitener . METHODS 50 adults were r and omized to Crest Night Effects , a 19 % sodium percarbonate gel that dries to form an adherent film , or a placebo gel without any peroxide source . The treatments were brush-applied at night , and removed the next morning with normal toothbrushing . Subjects were evaluated biweekly during the 6-week treatment period to evaluate initial and cumulative color change , and again , 4 weeks after completion of treatment to evaluate color relapse . Efficacy was determined by evaluating reduction in tooth yellowness ( delta b * ) , increase in tooth brightness ( delta L * ) and overall change relative to white ( delta W * ) from st and ardized digital images . Tolerability was assessed by examination and interview conducted at treatment and post-treatment visits . RESULTS Relative to baseline , the 19 % sodium percarbonate film group had significantly ( P < or = 0.013 ) whiter teeth after 2 weeks overnight use . For maxillary teeth , delta b * and delta L * means ( SD ) were : -1.35 ( 0.858 ) and 1.06 ( 0.886 ) , respectively . For m and ibular teeth , delta b * and delta L * means ( SD ) were : -1.27 ( 0.903 ) and 0.56 ( 0.790 ) , respectively . Relative to placebo , the 19 % sodium percarbonate group was significantly ( P < 0.005 ) better than placebo for delta b * , delta L * , and delta W*. There was a cumulative benefit with additional treatment , as evidence d by significant ( P < 0.0001 ) improvement in mean delta b * after the initial 2 weeks of treatment . Approximately 90 % of the 6-week cumulative color improvement was still evident after 4 weeks post-treatment . Tooth sensitivity ( 20 % of the peroxide group ) represented the only adverse event with increased occurrence over placebo , and these events were mild and fully resolved during/after treatment Tooth whitening is one of the most widely accepted esthetic procedures in dentistry . Various treatment options include in-office and prescribed at-home bleaching procedures , over-the-counter bleaching kits , and whitening dentifrices . This study evaluated and compared a 6 % hydrogen peroxide tooth bleaching gel delivered on polyethylene film ( HP ) with an 18 % carbamide peroxide brush-applied liquid gel ( CP ) . A total of 59 subjects completed this 2-week , examiner blind , r and omized , parallel group study . Both treatments were applied twice daily for 2 weeks according to the manufacturer 's instructions . Evaluations for oral safety and Vita tooth shade were conducted by a dental examiner at baseline and 2 weeks after product use . In addition , the ShadeVision System was used to determine changes in Vita shade and L*a*b * values . Based on both the examiner and ShadeVision System assessment s , both treatments significantly improved tooth shade . Improvements in Vita tooth shade based on the adjusted mean for HP were 2.64 ( P < 0.001 ) and 2.33 ( P < 0.001 ) for the examiner and ShadeVision System assessment s , respectively , compared with improvements of 1.04 ( P = .004 ) and 0.42 ( P = 0.029 ) for CP users , respectively . The difference between treatments was found to be significant for both the examiner ( P = .005 ) and ShadeVision ( P = .001 ) assessment s. Findings from the L*a*b * data derived from the ShadeVision System were in agreement with Vita assessment s , with significant differences for changes in L * , a * , and b * in favor of HP users ( P = .001 ) . In this study , the ShadeVision method of color analysis was relatively easy to use and demonstrated significant differences between 2 OTC whitening products using both Vitapan and L*a*b * means of assessment OBJECTIVES Transient sensitivity during bleaching is generally reported to affect 67 % of patients . While most people tolerate this sensitivity , some find it impossible to continue treatment . The purpose of this study was to determine the safety and efficacy of an experimental , low-sensitivity bleaching agent . METHOD AND MATERIAL S Twenty-two participants bleached for a minimum of 6 hours per night over a 2-week period . The bleaching agent used , Experimental Product E , is a 10 % carbamide peroxide gel containing potassium nitrate and sodium fluoride . Evaluations were performed at baseline and 1,2,13 , and 26 weeks . Color change was measured using a value-ordered Vita classic shade guide and a colorimeter . Sensitivity of the teeth , gingiva , tongue , and /or throat was measured daily using a patient log . RESULTS The median color change after 2 weeks was eight tabs . Approximately 36 % reported sensitivity during the active whitening phase of the study . As a group , participants reported sensitivity during 13.7 % of the total days spent whitening . CONCLUSION Experimental Product E was shown to be safe . Participants experienced minor sensitivity during the active bleaching phase only . Experimental Product E was shown to be an effective bleaching agent for the subjects tested in this study BACKGROUND The scientific literature is lacking in long-term clinical data on the duration of efficacy and post-treatment side effects of nightguard vital bleaching . PURPOSE This longitudinal clinical study was undertaken ( 1 ) to determine the clinical efficacy and duration of efficacy at 3 , 6 , and 47 months post treatment of a peroxide-containing whitening solution ; ( 2 ) to evaluate safety issues with respect to using a peroxide whitening solution ; and ( 3 ) to determine patients ' perceptions of the whitening technique . MATERIAL S AND METHODS This project was part of a nightguard vital bleaching study involving human participants . The study teeth for efficacy and duration of efficacy when using a 10 % carbamide peroxide solution were the four maxillary central and lateral incisors , with the tooth shade being taken from the middle third of the tooth . Safety issues evaluated were the changes in gingival index ( GI ) , plaque index ( PI ) , nonmarginal gingival index ( NMGI ) , nongingival oral mucosal index ( NGOMI ) , and tooth vitality ( TV ) . Radiographic changes of the study teeth and the patients ' perceptions of tooth sensitivity ( TS ) or gingival irritation ( Girr ) during treatment and post treatment were also evaluated . RESULTS The active 10 % carbamide peroxide whitening solution used in this study was effective in lightening teeth ( 98 % ) , and this effect was sustained at a mean of 47 months post treatment in 82 % of the participants . When evaluating safety issues , 66 % of the participants using the active solution reported TS or Girr . No one reported TS or Girr or any other adverse effects at the end of the study . CONCLUSIONS The results of this study concur with those of previously reported studies that nightguard vital bleaching using a 10 % carbamide peroxide whitening solution according to the manufacturer 's instructions is efficacious and safe , with minimal side effects . In addition , long-term shade retention was reported by 82 % of the participants at the end of the study , with no adverse side effects . CLINICAL SIGNIFICANCE Results of this study should reassure dentists that nightguard vital bleaching is a safe , effective , and predictable method to lighten teeth . The whitening effect lasted up to 47 months in 82 % of the patients , with no adverse side effects reported at the end of the study PURPOSE To clinical ly evaluate a new system for at-home tooth whitening ( Colgate Simply-White Whitening Gel ) , by comparing tooth color improvement and adverse event incidence after 14-days treatment . MATERIAL S AND METHODS 22 subjects ( aged 21 - 46 years ) were enrolled into the study . Tooth color and safety assessment s were conducted at baseline and following a 2-week at-home treatment . Efficacy was assessed using VITA shade scores . Safety evaluations were performed including the examination of plaque index ( PI ) , bleeding index ( BOP ) , gingival recession and dentin hypersensitivity . Statistical analysis was performed to determine the mean change from baseline . RESULTS The new whitening gel releasing 5.9 % hydrogen peroxide was significantly effective in lightening tooth shade . After only 2 weeks , patients enrolled in the study exhibited an overall mean 3.56-shade improvement from baseline , far superior than minimum values established in ADA Guidelines for the acceptance of peroxide-containing oral hygiene products . Periodontal health ( PI and BOP ) improved with time overall . Dentin hypersensitivity slightly increased , but it was very well tolerated . No patient discontinued study participation due to such an adverse event . Therefore , it was concluded that the new Colgate Simply White Clear Whitening Gel provided clinical ly proven , safe and effective at-home tooth whitening PURPOSE The purpose of this r and omized double-blind investigation was to clinical ly evaluate the effectiveness of a commercially available 3 % hydrogen peroxide tooth-whitening material ( ADS Tooth Whitening Gel , Applied Dental Sciences , Inc. , Lee , MA ) . The material was used over 2 weeks in a dentist-supervised , patient-applied application . MATERIAL S AND METHODS The evaluation was carried out in accordance with American Dental Association ( ADA ) Council on Scientific Affairs Acceptance Program Guidelines for Home-Use Tooth Whitening Products ( May 1998 ) . Sixty-five participants were r and omized into two groups ( active and placebo ) for a double-blind , placebo-controlled study . A custom application tray , scalloped without reservoirs , was fabricated for each participant . Tooth shades were documented by matching with the Vita shade guide ordered according to value and assigned a numeric ranking from 1 to 16 , darkest to lightest . Participants were supplied with the treatment solutions to use in the application tray . Duration of active treatment was 30 minutes 3 times a day for 2 weeks . Participants were evaluated at baseline , 1 week and 2 weeks treatment , and 12 and 26 weeks post-treatment . The statistical analysis used at each time point to determine the difference between the active and placebo groups based on the change in value was the two- sample t-test . Plaque and soft tissue indices were also recorded . RESULTS The teeth treated with 3 % hydrogen peroxide were significantly lighter at 2 , 12 , and 26 weeks ( p < or = .0140 , .0004 , and .0001 , respectively ) compared with the placebo group . The mean shade change was 4.2 Vita shade tabs at 2 weeks . At 26 weeks ( 6 months ) , the degree of whitening was 4.1 tabs PURPOSE Prescribed , patient-applied tooth lightening agents , or nightguard vital bleaching , typically utilizes a 10 % carbamide peroxide agent applied during nocturnal hours . The purpose of this r and omized double-blind study was to compare the amount of tooth color change in two groups of subjects using dentist-supervised , patient-applied 10 % carbamide peroxide gel . MATERIAL S AND METHODS One group used Opalescence ( Ultradent Products Inc. , South Jordan , Utah ) and the other NiteWhite Excel ( Discus Dental , Inc. , Los Angeles , California ) . Evaluation of tooth color for the six maxillary anterior teeth was done using a Vita shade guide at baseline , 1 , 2 , and 4 weeks . Subjects were instructed to apply the gel nocturnally using a custom-made soft tray 8 hours per day for 2 weeks . The 16 tabs of the shade guide were ranked according to value from darkest to lightest . The number ( 1 - 16 ) that correlated to the shade tab selected as the match for each tooth was the outcome variable . A Kruskal-Wallis one way analysis of variance on ranks was used . RESULTS The test revealed no statistically significant difference between Opalescence and NiteWhite Excel for lightening the teeth ( p = .807 ) . The color change was still significant after 2 weeks without further bleaching activity . The baseline evaluation of the maxillary incisors and canines for all subjects , regardless of group , demonstrated a significant shade difference , with the canines being darker . This difference was not seen after 2 weeks of active bleaching or at the 4-week evaluation . CLINICAL SIGNIFICANCE In this study comparing bleaching products , patients using Opalescence and NiteWhite Excel experienced a significant change in the color of their teeth relative to baseline values after 2 weeks of active treatment A 2-week , three-cell study was conducted to evaluate the tooth-whitening efficacy of the Colgate Platinum Professional Toothwhitening System vs Rembr and t Gel Plus ( a regimen of products consisting of a 10 % carbamide peroxide gel , a whitening toothpaste , and a mouthrinse ) , and a placebo paste . Seventy subjects completed this parallel , single-blind , three-compartment , r and omized clinical study . The subjects were balanced into two groups based on a minimal shade of A3 on the Vita shade guide and assigned a product . The duration of product usage was 1 hour twice daily for 2 weeks . Change in tooth color was measured by reflectance spectroscopy using a colorimeter . The readings were taken in the L * , a * , b * color space at the initiation , at 1 week , and at 2 weeks of the study . Calculation of color change ( delta E ) was performed using the color difference equation established by the Commission Internationale de L'Eclairage . Visual evaluation of shade changes was performed using the Vita shade guide . Results from this clinical study showed that Colgate Platinum was 77.7 % more effective at tooth whitening after 1 week and 41.8 % more effective after 2 weeks of treatment vs the Rembr and t regimen . Results showed that the Colgate product is significantly superior vs Rembr and t at increasing tooth whiteness ( increase in delta E ) . Shade guide changes showed an overall improvement of 7.08 Vita tabs for the Colgate product and 5.12 Vita tabs for the Rembr and t regimen In this clinical trial of nightguard vital bleaching for six weeks , 92 percent of the patients experienced some lightening of treated teeth . About 97 percent of patients with teeth stained through aging , inherent discoloration , brown fluorosis or trauma experienced lightening , as did 75 percent with tetracycline-stained teeth . Sixty-six percent experienced side effects , which resolved in 24 to 48 hours . Earliest re-treatment was done after one year in less time . Minimal color change occurred for 74 percent after 1 1/2 years and 62 percent after three years PURPOSE To evaluate the clinical response of a low peroxide concentration bleaching system with a desensitizing agent relative to a marketed control . MATERIAL S AND METHODS After balancing for baseline color and age , 34 healthy adult volunteers were r and omized to one of two marketed bleaching systems , 5 % carbamide peroxide bleaching gel + potassium nitrate in a custom tray ( Colgate Platinum Gentle Plus ) or 6.0 % hydrogen peroxide bleaching strips ( Crest Whitestrips ) . Daily contact time was 6 - 8 hours for the tray system compared to 1 hour for the strip system , following manufacturers ' instructions . Whitening was measured objective ly using digital image analysis to assess L*a*b * after 7 days , while tolerability was assessed through interview and examination . RESULTS The predominantly female ( 85 % ) and non-smoking ( 91 % ) study population ranged from 20 - 47 years of age . Both treatments yielded a statistically significant ( P < 0.001 ) whitening benefit with respect to reduction in yellowness ( Ab * ) and improvements in other color endpoints ( deltaL * , deltaE * , and a new parameter , deltaW * ) compared to baseline . The strip group experienced greater color improvement on average for all color parameters in the study . After 7 days treatment , the adjusted mean deltab * was -1.24 in the strip group and -0.65 in the tray group , with these groups differing significantly ( P = 0.04 ) . Tooth sensitivity was reported by 13 % of subjects using the hydrogen peroxide strips , compared to 22 % of subjects using the carbamiide peroxide potassium nitrate tray system . No subjects discontinued treatment early due to an adverse event Professionally dispensed , at-home tooth whitening began with 10 % carbamide peroxide gels applied to the dentition with custom-made trays . In the 1990s , higher-concentration carbamide peroxide gels were introduced to achieve faster results . Today , 15 % and 20 % carbamide peroxide gels are commonly used . Recently , a new vital tooth-whitening technique that uses a flexible strip rather than a tray to apply a 5.3 % hydrogen peroxide whitening gel was introduced . The new strip-based product was shown to provide whitening equivalent to a 10 % carbamide peroxide tray with half the wear time . In addition , the strip eliminated the need to custom fabricate trays for each patient . This article provides an overview of a professionally distributed strip-based whitening system and review s some of the clinical data which supports the efficacy of the product . This new whitening system includes 42 m and ibular and 42 maxillary strips at a higher concentration of 6.5 % hydrogen peroxide . In addition , the system also includes a novel dual-action whitening dentifrice to prevent future staining postbleaching and an extrasoft toothbrush . Clinical ly , the professionally distributed strip-based whitening system provided 96 % more efficacy than a popular carbamide plus hydrogen peroxide ( equivalent to 10 % carbamide peroxide ) tray system and 52 % more whitening than the 5.3 % hydrogen peroxide strip system OBJECTIVES The aim of this study was to compare the effect on oral soft tissue of a self-applied tooth whitening gel containing 6 % hydrogen peroxide ( Xtra White ) with a marketed paint-on whitening gel containing 18 % carbamide peroxide ( Colgate Simply White ) after 2-weeks of using products four times daily . METHODS A 2-week , examiner-blind , stratified , parallel design clinical trial was conducted . Twenty subjects were divided into two groups , balanced according to age and gender . Subjects followed a 2-week , twice-daily regimen of brushing with st and ard fluoride toothpaste and applied gel product to facial aspects of six upper and six lower incisors/canines , twice in succession with 30 min between applications . Soft tissue examinations were performed on Day 1 , before the first application of the test products , and on Day 2 , 5 , 8 and 15 . RESULTS During the 2-week treatment period , twelve adverse reactions were recorded as potentially attributable to the study products , evenly split between the two test groups . All reports were mild in symptoms and resolved without the need of medical intervention . None of the subjects experiencing an adverse event requested to be withdrawn from the study . CONCLUSIONS Under the exaggerated use conditions of this test , there was no evidence to suggest that either of the whitening gels produced irritation that was building or developing during the course of the study . It is concluded that both products are safe for their intended use PURPOSE To compare the whitening effectiveness of two professional vital bleaching systems in a r and omized clinical trial . MATERIAL S AND METHODS Balancing for baseline color , 6 9 adult volunteers were r and omized to either a whitening strip containing 6.5 % hydrogen peroxide ( Professional Crest Whitestrips ) or a custom tray-based system using both hydrogen and carbamide peroxide ( Nite White Excel2 ) . Total contact time was 21 hours for the strip system and 28 hours for the 10 % carbamide peroxide equivalent tray system . Whitening response was measured objective ly as L*a*b * from digital images of the maxillary anterior teeth . RESULTS Both treatments result ed in significant ( P < 0.01 ) improvements in yellowness ( deltab * ) , brightness ( deltaL * ) and overall color ( deltaE * ) . For between group comparisons , strip subjects had a statistically significant or directionally favorable whitening response relative to the tray system at intermediary time points , while at the end-of-treatment , the strip group had highly statistically significant ( P < or = 0.005 ) , superior whitening response for all color parameters measured in the study . Both treatments were generally well tolerated , with 35 - 40 % of the subjects in each group reporting minor tooth sensitivity or gingival irritation Bleaching offers a non-interventive way of improving the appearance of sound , yet discolored anterior teeth . Until recently , the whitening agent was applied using a tray , but now other methods of delivering whitening agents , such as those using brush applicators , are available . This study investigated the tooth whitening efficacy of two novel , self-applied tooth whitening systems containing either 18 % ( Group 1 ) or 16.4 % ( Group 2 ) carbamide peroxide . Ninety-five subjects , ranging in age from 18 to 70 with anterior teeth A3 or darker , were recruited and r and omly allocated to a group . The subjects were instructed to apply the formulation to all maxillary anterior teeth after brushing in the morning and evening . At baseline , two weeks and six months the upper six anterior teeth of the subjects were measured using the Vita shade guide tab system . In addition , the gingival health of the labial surfaces of the upper six anterior teeth was assessed using the Loee and Silness Gingival index ( Loee & Silness , 1963 ) at baseline and at two weeks . The mean ( SD ) reduction in shade guide scores was 4.1 ( 2.4 ) shade guide tabs for subjects in Group 1 , compared to 3.7 ( 2.6 ) shades for those in Group 2 . This difference was not statistically significant ( p=0.5 ) . During the course of study , the gingivitis scores reduced from a mean ( SD ) of 0.91 ( 0.62 ) at baseline to 0.44 ( 0.55 ) at final examination ( 48 % reduction ) . At the six-month recall , the mean ( SD ) reduction in shade guide scores was 2.3 ( 2.7 ) shade guide tabs for subjects in Group 1 , compared to 2.5 ( 2.5 ) shades for those in Group 2 . The different concentrations tested were found to be equally effective in improving the whiteness of upper anterior teeth by approximately four shades over a two-week period and the majority of the whitening benefit ( c.60 % ) was sustained at six-month recall OBJECTIVE The purpose of this study was to evaluate the degree of color change , any rebound effect , and sensitivities associated with using 2 different concentrations of carbamide peroxide in vivo . METHOD AND MATERIAL S Twenty-five subjects used 10 % and 15 % agents in trays for 14 days on different sides of their maxillary arches . Subjects returned in 3 days and at 1 , 2 , 3 , and 6 weeks for evaluation of color change and rebound effect . Shade matching , photographic means , and a colorimeter were used for evaluation . Subjects self-reported gingival and tooth sensitivity on a scale of 1 ( no sensitivity ) to 5 ( severe sensitivity ) . RESULTS After 2 weeks , delta L * , delta a * , delta b * , delta E * and delta shade guide rank means for the 10 % whitening agent were 6.50 , -1.37 , -4.63 , 8.79 , and -15.40 , respectively ; for the 15 % agent , they were 8.72 , -1.63 , -5.90 , 11.03 , and -16.59 , respectively . After 6 weeks , delta L * , delta a * , delta b * , delta E * , and delta shade guide rank means for the 10 % whitening agent were 3.04 , -0.99 , -3.19 , 5.13 , and -13.13 , respectively ; for the 15 % agent , they were 3.48 , -1.01 , -3.60 , 5.58 , and -13.65 , respectively . Means for gingival sensitivity were 1.18 and 1.21 for the 10 % and 15 % agents , respectively ; means for tooth sensitivity were 1.21 and 1.26 for the 10 % and 15 % agents , respectively . CONCLUSION All 3 methods of evaluation revealed a significant difference in the tooth lightness achieved by 10 % and 15 % products at 2 weeks but no significant difference at 6 weeks . No statistically significant difference was found in gingival or tooth sensitivity A new approach to assess color change in teeth involves application of the Minolta CR-221 Chroma Meter . The process has been assessed in vitro by Dr. Stephen Rosenstiel of Ohio University and by Dr. Robert Seghi of the University of California School of Dentistry . The purpose of this study was to develop a technique to assess the tooth-whitening effects of peroxides on teeth in vivo , using a small-area colorimeter . Twenty male and female subjects participated . Study casts were made from alginate impressions . Two maxillary , white , polyvinyl siloxane , custom-postioning splints were fabricated for each subject . Each splint was modified to accept exactly the head of the colorimeter to a window exposing the middle one third of the facial surface of one central incisor . The coloimeter converts all colors within the range of human perception into a common numerical code . The use of the positioning splint allowed the research ers to reposition the colorimeter precisely for multiple reading each time measuremehts were taken . The color parameters were recorded in the L*a*b * color space . This method shows that multiple measurements on the same subject are consistent and statistically accurate . The st and ard deviation for L * ( lightness ) values was 0.22 . This technique showed quantitatively the whitening effect on teeth to be increase in L * and a decrease in a * ( red ) and b * ( yellow ) . The mean color difference ( deltaE ) for the 3-week study was 5.07 A double-blind , 3-week , r and omized , placebo-controlled , parallel-group clinical trial was conducted to evaluate the tooth-whitening efficacy of a novel nontray , " paint-on " liquid whitening gel containing 18 % carbamide peroxide ( Colgate Simply White Clear Whitening Gel ) . Efficacy was based on measured Vita tooth-shade scores collected at baseline and after 2 and 3 weeks of product use . Eighty healthy volunteers were balanced into 2 groups based on gender , age , and shade scores ( A3 or higher ) . The duration of product usage was 30 minutes , twice daily , for 3 weeks . Results from this clinical study showed that subjects ' teeth in the liquid whitening gel-treated group exhibited an overall mean 3.84-shade improvement and a 3.5-shade difference compared with teeth in the placebo gel group ( statistically significant , P < .05 ) after 3 weeks . Furthermore , this improvement exceeds the minimum requirement to cl aim " clinical efficacy " as established by the " Guidelines for the Acceptance of Peroxide-Containing Oral Hygiene Products , " published by the American Dental Association in 1994 . Therefore , it can be concluded that Colgate Simply White Clear Whitening Gel significantly whitens teeth A r and omized , examiner-blind , parallel-group , 3-week clinical trial evaluated the efficacy and safety of 3 , popular , direct-to-consumer whitening products : a paint-on gel , a whitening dentifrice , and whitening strips . Both the paint-on gel ( 18 % carbamide peroxide ) and the whitening strips ( 6 % hydrogen peroxide ) were peroxide-based systems , while the dual-phase whitening dentifrice incorporated surface cleaning agents and sodium fluoride , but contained no peroxide . Treatment consisted of twice-daily use over 3 weeks following label instructions , except that strips were applied only during the first 14 days as per the manufacturer 's instructions . Tooth color was measured on the maxillary anterior teeth from polarized digital images . Safety was assessed by examination and subject report . A total of 48 healthy adults were r and omized , and 42 completed 1 or more post-baseline visits . For the primary efficacy variable delta b * , the adjusted mean + /- st and ard error reduction in yellowness was -0.06 + /- 0.131 for the dentifrice with no peroxide and -0.21 + /- 0.109 for the 18 % carbamide peroxide paint-on gel , compared with -2.53 + /- 0.244 for the whitening strip control . Only the strip group exhibited significant ( P < 0.0001 ) delta b * improvement . Between-group comparisons demonstrated significant and improved whitening for the strip treatment compared with the whitening dentifrice or paint-on peroxide gel , as evidence d by the more than 2-unit improvement in delta b * at week 3 . Regardless of the parameter ( delta b * , delta L * , delta a * , or delta E * ) , this represented a significant ( P < 0.0001 ) color improvement for the whitening strips relative to both of the comparative treatments . There were no significant differences in color improvement for the 18 % carbamide peroxide paint-on gel used for up to 3 weeks continuously , compared with normal brushing with a dual-phase whitening dentifrice . All products were well tolerated , with no subjects discontinuing treatment early because of adverse events . In head-to-head testing conditions , 14-day use of the 6 % hydrogen peroxide whitening strips result ed in superior improvement in tooth color compared with either of the experimental controls BACKGROUND Vital tooth bleaching for esthetic reasons has gained in popularity during the last few years . However , few studies have investigated the efficacy of daytime bleaching products . The purpose of this double-blind in vivo study was to evaluate the efficacy of 20 percent carbamide peroxide , or CP , and 7.5 percent hydrogen peroxide , or HP , during daytime use . The degree of color change , any color relapse , and tooth or gingival sensitivity were evaluated . METHODS Twenty-four patients participated in this study . The bleaching gels were r and omly applied to the right and left maxillary anterior teeth . Patients were shown how to place the two bleaching agents in a custom tray for one hour , twice a day for two weeks . Patients returned in one , two , three , six and 12 weeks for color evaluation with the colorimeter and shade guides as well as to have color slide photographs taken . The authors evaluated sensitivity by asking the patients to record daily for 21 days any tooth or gingival sensitivity they experienced . RESULTS Use of the 20 percent CP result ed in significantly more lightness than the 7.5 percent HP during the first 14 days of the study , but at the end of the study , there was no significant difference between products with regard to tooth lightness . In addition , the authors found no statistically significant difference between products with regard to gingival or tooth sensitivity . CONCLUSIONS Both CP and HP are effective at-home bleaching agents when daytime bleaching is preferred . CLINICAL IMPLICATION S Dentists who choose to use daytime bleaching can select either CP or HP BACKGROUND A profusion of commercial bleaching systems exists on the market today , but there are few clinical comparisons of these systems . METHODS In this study , three different commercial 10 % carbamide peroxide bleaching systems were used by 24 patients in an overnight protocol for two weeks . Each patient used two of the bleaching products simultaneously in a side-by-side comparison . RESULTS The mean onset of tooth whitening was 2.4 + /- 1.7 days . Tooth sensitivity was the most frequent side effect , as 64 % of the patients reported tooth sensitivity occurring after 4.8 + /- 4.1 days and lasting for 5.0 + /- 3.8 days . Although intrapatient differences were recorded for the three commercial 10 % carbamide peroxide bleaching systems by the patients , there were no statistical differences in the time of onset of subjective tooth whitening and the onset , frequency and duration of tooth sensitivity among the three commercial bleaching systems when compared pairwise or independently ( p < 0.05 ) . CONCLUSION Selection of which bleaching product to use should be based on the concentration of the active ingredient , the viscosity of the product and other marketing features . Further research is needed to investigate the causes of tooth sensitivity and methods to reduce its severity and frequency PURPOSE This r and omized clinical trial compared the clinical efficacy and tolerability of 2 marketed self-directed vital tooth-whitening systems . MATERIAL S AND METHODS Balancing for baseline tooth color , self-reported coffee/tea use , and age , 57 adult volunteers were r and omized to either a whitening strip containing 6 % hydrogen peroxide or a tray-based 10 % carbamide peroxide/dentifrice/mouth rinse combination system . Following the manufacturer 's directions , the strip group bleached twice daily for 30 minutes , whereas the tray group bleached twice daily for 20 - 30 minutes , preceded by tooth brushing with a whitening dentifrice and followed by mouth rinsing with a whitening solution . Treatment extended for 14 days , with evaluation at day 7 and again at day 14 . Whitening response was measured objective ly as L*a*b * from st and ardized digital images of maxillary anterior teeth . Tolerability was assessed by oral examination and subject interview . Efficacy comparisons were made using analysis of covariance , whereas tolerability was compared using the nonparametric Wilcoxon rank-sum test . RESULTS Both treatments result ed in statistically significant ( P < 0.01 ) improvements from baseline for all color parameters . For between-group comparisons , the 6 % hydrogen peroxide strips yielded a nearly 3-fold reduction in yellowness ( deltab * ) , a nearly 2-fold improvement in lightness ( deltaL * ) , 2.6 times greater redness reduction ( deltaa * ) , and a more than 2-fold change in overall color ( deltaE * ) compared to the tray-based combination system . Between-group comparisons were statistically significant for the all color parameters at both the day 7 and day 14 evaluations ( P < 0.001 ) . In general , 7-day use of the whitening strips provided significantly greater color improvement relative to the combination dentifrice/gel/rinse system at day 14 . In addition , the groups differed significantly ( P < 0.05 ) in bleaching tolerability severity-days , with the strip system demonstrating better overall tolerability compared to the combination system . CONCLUSIONS The single-step 6 % hydrogen peroxide strips demonstrated better overall clinical response , in terms of both tooth-whitening efficacy and tolerability , than the multiple-step tray-based combination system A double-blind experiment assessed the efficacy , longevity and safety of a tooth whitener in young adults . Significant color changes occurred after active treatment but were substantially reversed after one week . No permanent changes were found in either pulpal or gingival health PURPOSE The research evaluated the peroxide concentration whitening response following self-directed use of whitening strips over a 28-day period . METHODS A r and omized , double-blind , parallel group clinical study was conducted . 37 healthy adult volunteers were r and omly assigned to one of three groups based on tooth color at screening : 1.8 % hydrogen peroxide strips ( HPS ) , 3.3 % HPS or 5.3 % HPS . Subjects applied the assigned maxillary strips twice per day for 30 minutes over 28 days . Tooth color was evaluated at day 7 , 14 and 28 from digital images of the maxillary six anterior teeth using a st and ard method . Treatments were compared using analysis of covariance ( adjusting for baseline ) at a 0.05 level of significance . RESULTS Hydrogen peroxide at concentrations ranging from 1.8 - 5.3 % result ed in significant ( P < 0.05 ) color improvement versus baseline as early as Day 7 . There was a concentration-response for reduction in yellowness ( deltab * ) and lightness improvement ( deltaL * ) at all timepoints , favoring the higher concentrations . While the concentration-whitening relationship approached a linear response at Day 7 , continued treatment result ed in incremental color improvement . All three peroxide concentrations were well tolerated , and no subjects discontinued early due to a treatment-related adverse event A r and omized , single-center , double-blind , parallel-group , placebo-controlled trial evaluated the whitening efficacy and safety of 2-week , twice-daily use of a 5.3 % hydrogen peroxide tooth-bleaching gel delivered on polyethylene film . Efficacy was based on change in Vita shade scores from baseline to the end of treatment . Thirty-three patients in each group completed treatment . Use of the peroxide-containing gel led to a mean change in baseline Vita shade score of -3.70 + /- 0.35 , compared with a change of -0.87 + /- 0.24 after use of a placebo gel . After adjustment for baseline scores , the mean difference in shade change between the peroxide gel-treated group and placebo-treated group was -2.85 + /- 0.41 ( P < 0.0001 ) . Both treatments were generally well tolerated . The strips offer ease of use , comfort , and shorter duration of wear compared with other at-home bleaching systems A three-cell , r and omized , parallel , investigator-blinded clinical trial was conducted to compare the efficacy and safety of three professional at-home tooth whitening systems , including Crest Professional Whitestrips ( 6.5 % H2O2 ) , Day White 2 ( 7.5 % H2O2 ) and Nite White Excel 2 ( 16 % carbamide peroxide equivalent ) . Ninety subjects were r and omly assigned to three groups ( 30/group ) . Subjects were instructed to use the assigned whitener following the manufacturers ' instructions . Clinical examinations at baseline , and on days 3 , 7 , 14 , and 18 ( Day White ) , or 21 ( Crest Professional Whitestrips and Nite White ) included the following parameters : 1 ) oral tissues ; 2 ) tooth shade by the Vitapan Classical shade guide ; 3 ) tooth shade by a chromameter with a jig ; and , 4 ) tooth sensitivity and gingival irritation . The results showed significant shade reductions with time in all three groups . Nite White result ed in significantly greater shade reductions in periods between days 7 , 14 , or 21 and baseline than did the other two systems . Tooth sensitivity and gingival irritation , which were mostly mild and transient , occurred in all groups . It is concluded that all three whitening systems evaluated are effective and safe . Nite White Excel is superior to the other two systems because it provides a greater whitening efficacy with comparable or lower incidence of tooth sensitivity and gingival irritation This in vivo study evaluated the variation of tray fabrication ( trays constructed with or without reservoirs ) on the degree of color change of teeth and sensitivities associated with using a 15 % carbamide peroxide bleaching agent for two hours once daily for 14 days . Patients returned in one , two , three , six and 12 weeks . Color changes were evaluated by subjective shade matching , comparing clinical photographs and through measurements obtained using a color-measuring device . Subjects were asked to keep a daily record of any tooth and gingival sensitivity on the right and left side of their maxillary dental arch for three weeks . Colorimeter data showed that teeth lightened with agent with reservoirs were significantly lighter than teeth lightened with the same agent without reservoirs . However , the amount of lightening was below the threshold of visual differentiation . Shade guide and slide photography data showed no significant differences between teeth lightened with agent with reservoirs compared to teeth lightened with the same agent without reservoirs . In addition , no significant differences in tooth and gingival sensitivity were found between the tray side with reservoirs and those without reservoirs OBJECTIVE Recently , a novel paint-on liquid whitening gel -- Colgate Simply White Clear Whitening Gel -- which contains 18 % carbamide peroxide , has been developed as a self-administered tooth bleaching system . The purpose of the present study was to determine the efficacy and safety of this product using alternate exaggerated or simplified treatment regimens . METHODOLOGY This was a three-week clinical trial using a parallel , double-blind , stratified protocol with three different instructions for application : 1 ) twice-daily , no air-drying , and 15 minutes without eating/drinking ; 2 ) three times daily , 30-second air-drying and 30 minutes without eating/drinking ; or 3 ) four times daily , 30-second air-drying and 30 minutes without eating/drinking . One-hundred and twenty ( 120 ) healthy volunteers were balanced into three equal groups based on shade scores ( A3 or darker ) . Clinical evaluations ( shade guide , oral tissue health , gingival index and visual analog sensitivity score ) were performed on each group at baseline and weekly for the next 21 days . At the conclusion of the study , a survey of the subjects ' opinions on their assigned product regimen was also conducted . RESULTS Subjects who used Colgate Simply White Clear Whitening Gel three and four times daily achieved the greatest shade improvement ( 5.88 + /- 1.53 shades , and 5.57 + /- 1.54 , respectively ) . However , these values were only about one shade better than the value observed for the more convenient , twice-daily , " no-dry " regimen ( 4.51 + /- 1.77 shades ) , though they were statistically significant ( p < 0.05 ) . The result for the four-times daily protocol was not statistically different from the three-times group . Also , no differences were observed between the groups concerning oral tissue health , gingival index or tooth sensitivity , and no adverse effects were observed or reported regardless of the regimen used . Surveys completed by the subjects showed that those who used the twice-daily , " no-dry " regimen found the product to be the easiest to use , the most comfortable and the most pleasant tasting . CONCLUSION It can be concluded from the clinical data that three or four applications of Colgate Simply White Clear Whitening Gel per day provided better efficacy . In addition , the use of the whitening gel twice daily , even without " dry time " and only 15 minutes without eating/drinking , yielded results that were comparable to previously reported results using the original on-label directions . The potential additional benefit to the " simplified regimen " is that it was perceived to be the most convenient and comfortable . The use of Colgate Simply White Clear Whitening Gel up to four times daily for up to three weeks is also safe , and the tendency of abusing the product with more frequent daily use may be deterred by the inconvenience reported by the study subjects OBJECTIVE A 6-month , double-blind study was undertaken to assess the efficacy and safety of a 10 % carbamide peroxide gel design ed for at-home tooth bleaching . METHOD AND MATERIAL S Sixty patients were r and omized into two equal subgroups balanced by age , gender , and oral health status . Shade guide measurements , color transparency photographs , and colorimeter readings were taken and evaluated at baseline and 1 , 2 , 3 , 6 , 12 , and 24 weeks . The active phase of treatment lasted 14 days . RESULTS At 22 weeks postbleaching ( week 24 of the study ) , patients receiving the active agent had a 14.1 rank order difference in the shade guide from baseline , and 66 % had a clinical ly observable color change as determined by photographic assessment . They also had a measurable , statistically significant color change from baseline to 6 months of delta E * = 5.0 . The tooth color of maxillary incisors stabilized at week 6 and maxillary canines at week 12 . The mean color change lost from weeks 2 to 24 was 45 % ( in delta E * ) . Transient tissue and tooth sensitivity , noted in some patients , resolved after treatment was completed . CONCLUSION The product tested is an effective and safe tooth-whitening agent This double-blind , r and omized , controlled clinical trial was design ed to evaluate the efficacy and soft tissue effects of nightguard ( mouthguard ) vital bleaching . Subjects were assigned to one of two treatment groups , overnight ( insertion of mouthguard at bedtime ) or 3-hour ( replenishment of test solution at hourly intervals for a total of 3 hours exposure daily ) . The experimental solutions included two products that are specifically design ed for tooth bleaching , one product that is marketed as an oral antiseptic , and a control solution ( glycerin ) . Each subject participated for a 3-week period . Tooth color analysis ( shade determination ) was done at baseline and the end of the treatment . Gingival and Plaque Indices were recorded at baseline and at the end of each week of study . Results indicated that the bleaching treatment was effective in most cases and caused no tissue inflammation or significant tooth sensitivity . The mean Gingival and Plaque Indices were generally lower ( denoting improvement ) at the end of treatment . Patient satisfaction with the procedure was high PURPOSE To evaluate the efficacy and safety of a new 5.9 % hydrogen peroxide liquid , invisible gel , ( Colgate Simply-White Whitening Gel ) . METHODS A total of 30 subjects were enrolled into the study and divided into two treatment groups ( Colgate vs. placebo gel ) . Efficacy was assessed using VITA shade scores and safety evaluations were performed including the examination of plaque index ( PI ) , bleeding index ( BOP ) , gingival recession and dentin hypersensitivity . Statistical analysis was performed to determine the mean change from baseline . RESULTS The new whitening gel containing 5.9 % hydrogen peroxide was significantly effective in lightening tooth shade . After only 2 weeks , patients enrolled in the study exhibited an overall mean 4.48-shade improvement from baseline , which was significantly greater than placebo group and far exceeded the ADA minimum requirements to cl aim " clinical efficacy " . In the new Colgate Simply White Clear Whitening Gel group , periodontal health ( PI and BOP ) improved with time overall . Moreover , dentin hypersensitivity did not significantly increase , and all treatments were generally well tolerated . CLINICAL SIGNIFICANCE The new Colgate Simply White whitening gel containing 5.9 % hydrogen peroxide allowed consistent bleaching using minimal contact time , without adversely impacting overall tolerability The objective of this r and omized , controlled , examiner-blind , parallel-group clinical study was to determine whether a tooth-whitening gel ( Colgate Simply White Night Clear Whitening Gel ) can significantly lighten teeth when used once daily at night , as compared with a commercially available dentifrice . Following a baseline tooth shade evaluation using the VITA Shade Guide , qualifying adult male and female subjects from the Buffalo , New York area were r and omized into 2 treatment groups , which were balanced for baseline VITA Shade Guide scores , gender , and age . The treatment groups were : ( 1 ) a commercially available dentifrice only ; and ( 2 ) a tooth-whitening gel in addition to a commercially available dentifrice . Subjects assigned to the 2 groups were given the dentifrice and a soft-bristled toothbrush . In addition , subjects in one of the groups were given the tooth-whitening gel . All subjects were instructed to brush their teeth for 1 minute twice daily ( morning and evening ) with the dentifrice . The subjects in the group also using the tooth-whitening gel were further instructed to apply the gel once daily at night , as per manufacturer instructions . Evaluations of tooth shade for each subject were repeated after 2 weeks , and again after 3 weeks of product use . In addition , evaluations of tooth shade for subjects using the tooth-whitening gel were later conducted at 6 months after product use . Seventy-five subjects complied with the protocol and completed the study . At the 2-week and 3-week examinations , subjects using the tooth-whitening gel and dentifrice exhibited statistically significant ( P < .05 ) tooth shade lightening relative to baseline tooth shade . Furthermore , at the 2-week and 3-week examinations , subjects using the tooth-whitening gel exhibited statistically significant ( P < .05 ) tooth shade lightening relative to subjects using only the dentifrice . In addition , the 6-month-postuse examination showed that subjects using the tooth-whitening gel exhibited statistically significant ( P < .05 ) tooth shade lightening relative to baseline , thereby maintaining the tooth shade lightening that was evident at 3 weeks . The results of this clinical study indicate that after once-daily use at night for 2 or 3 weeks , the tooth-whitening gel provided statistically significant tooth shade lightening relative to baseline tooth shade for up to at least 6 months and also provided statistically significant tooth shade lightening relative to a commercially available dentifrice after 2 and 3 weeks of product use The safety and efficacy of a home-use carbamide peroxide tooth-whitening procedure were evaluated in a double-blind experimental design . Fifty-two adults were r and omly assigned to experimental and control ( placebo gel ) groups . The products were applied in a custom-fitted tray and used for 5 consecutive nights in accordance with the manufacturer 's recommendations . Tooth color changes from baseline were measured with a small-area colorimeter . Concurrently , electric pulp test and periodontal indices were measured . At the end of 6 months , the teeth in the active group had a statistically significant greater mean color change that did the placebo controls . The mean color change differed significantly by tooth type . No statistically significant changes in vitality , sulcus depth , or Gingival Index were found in the treatment group |
12,427 | 29,942,576 | Results Review of these texts reveals ambivalence in the appraisal of mHealth ; essentially , the critical stance in general analyses/overviews is absent from project assessment s. Especially weak evidence concerning sustainability and scalability is stressed in overviews .
Project assessment s are more optimistic .
Their analysis suggests a causal connection between simplicity and success .
Effective interventions are thus characterized by straightforward design and modest objectives .
Greatest impediments of impact are general technology-related issues and intervention inappropriateness due to insufficient underst and ing of beneficiaries and specific context of use ( circumstantial complications ) .
Conclusion Distinguishing between these two categories of complications helps to break the deadlock that marks the mHealth debate and add nuance to cl aims that mHealth 's evidence base is weak . | Background Africa is labelled the world 's fastest-growing ‘ mobile region ’ .
Considering such growth and the fragility of the continent 's healthcare , mHealth has flourished .
This review explores mHealth for community health in Africa in order to assess its still ambivalent evidence base . | Background The WelTel Kenya1 trial demonstrated that text message support improved adherence to antiretroviral therapy ( ART ) and suppression of HIV-1 RNA load . The intervention involved sending weekly messages to patients inquiring how they were doing ; participants were required to respond either that they were well or that there was a problem . Objectives 1 ) Describe problems participants identified through mobile phone support and reasons why participants did not respond to the messages ; 2 ) investigate factors associated with indicating a problem and not responding ; and 3 ) examine participant perceptions of the intervention . Design Secondary analysis of WelTel Kenya1 trial data . Methods Reasons participants indicated a problem or did not respond were extracted from the study log . Negative binomial regression was used to determine participant characteristics associated with indicating a problem and non-response . Data from follow-up question naires were used to describe participant perceptions of the intervention . Results Between 2007 and 2009 , 271 participants generated 11,873 responses ; 377 of which indicated a problem . Health issues were the primary reason for problem responses ( 72 % ) . Rural residence ( adjusted incidence rate ratio [ IRR ] 1.96 ; 95%CI 1.19–3.25 ; p = 0.009 and age were associated with indicating a problem ( adjusted IRR 0.63 per increase in age group category ; 95%CI 0.50–0.80 ; p<0.001 ) . Higher educational level was associated with a decreased rate of non-response ( adjusted IRR 0.81 ; 95%CI 0.69–0.94 ; p = 0.005 ) . Of participants interviewed , 62 % ( n = 129 ) stated there were no barriers to the intervention ; cell phone issues were the most common barrier . Benefits included reminding patients to take medication and promoting a feeling that “ someone cares ” . Conclusions The WelTel intervention enabled frequent communication between clinicians and patients during the WelTel Kenya1 trial . Many patients valued the service for the support it provided , with health-related concerns comprising the majority of problems identified by participants . Few sociodemographic characteristics were associated with participant engagement in the intervention Background The World Health Organization now recommends parasitological confirmation for malaria case management . Rapid diagnostic tests ( RDTs ) for malaria are an accurate and simple diagnostic to confirm parasite presence in blood . However , where they have been deployed , adherence to RDT results has been poor , especially when the test result is negative . Few studies have examined adherence to RDTs distributed or purchased through the private sector . Methods The Rapid Examination of Malaria and Evaluation of Diagnostic Information ( REMEDI ) study assessed the acceptability of and adherence to RDT results for patients seeking care from private sector drug retailers in two cities in Oyo State in south-west Nigeria . In total , 465 adult participants were enrolled upon exit from a participating drug shop having purchased anti-malaria drugs for themselves . Participants were given a free RDT and the appropriate treatment advice based on their RDT result . Short Message Service ( SMS ) text messages reiterating the treatment advice were sent to a r and omly selected half of the participants one day after being tested . Participants were contacted via phone four days after the RDT was conducted to assess adherence to the RDT information and treatment advice . Results Adherence to RDT results was 14.3 percentage points ( P-val < 0.001 ) higher in the treatment group who were sent the SMS . The higher adherence in the treatment group was robust to several specification tests and the estimated difference in adherence ranged from 9.7 to 16.1 percentage points . Further , the higher adherence to the treatment advice was specific to the treatment advice for anti-malarial drugs and not other drugs purchased to treat malaria symptoms in the RDT-negative participants who bought both anti-malarial and symptom drugs . There was no difference in adherence for the RDT-positive participants who were sent the SMS . Conclusions SMS text messages substantially increased adherence to RDT results for patients seeking care for malaria from privately owned drug retailers in Nigeria and may be a simple and cost-effective means for boosting adherence to RDT results if and when RDTs are introduced as a commercial retail product Background Low rates of adherence to artemisinin-based combination therapy ( ACT ) regimens increase the risk of treatment failure and may lead to drug resistance , threatening the sustainability of current anti-malarial efforts . We assessed the impact of text message reminders on adherence to ACT regimens . Methods Health workers at hospitals , clinics , pharmacies , and other stationary ACT distributors in Tamale , Ghana provided flyers advertising free mobile health information to individuals receiving malaria treatment . The messaging system automatically r and omized self-enrolled individuals to the control group or the treatment group with equal probability ; those in the treatment group were further r and omly assigned to receive a simple text message reminder or the simple reminder plus an additional statement about adherence in 12-hour intervals . The main outcome was self-reported adherence based on follow-up interviews occurring three days after treatment initiation . We estimated the impact of the messages on treatment completion using logistic regression . Results 1140 individuals enrolled in both the study and the text reminder system . Among individuals in the control group , 61.5 % took the full course of treatment . The simple text message reminders increased the odds of adherence ( adjusted OR 1.45 , 95 % CI [ 1.03 to 2.04 ] , p-value 0.028 ) . Receiving an additional message did not result in a significant change in adherence ( adjusted OR 0.77 , 95 % CI [ 0.50 to 1.20 ] , p-value 0.252 ) . Conclusion The results of this study suggest that a simple text message reminder can increase adherence to antimalarial treatment and that additional information included in messages does not have a significant impact on completion of ACT treatment . Further research is needed to develop the most effective text message content and frequency . Trial Registration Clinical Trials.gov This paper presents the results of a qualitative study to investigate the perceptions and experiences of health workers involved in a a cluster-r and omized controlled trial of a novel intervention to improve health worker malaria case-management in 107 government health facilities in Kenya . The intervention involved sending text-messages about paediatric outpatient malaria case-management accompanied by “ motivating ” quotes to health workers ’ mobile phones . Ten malaria messages were developed reflecting recommendations from the Kenyan national guidelines . Two messages were delivered per day for 5 working days and the process was repeated for 26 weeks ( May to October 2009 ) . The accompanying quotes were unique to each message . The intervention was delivered to 119 health workers and there were significant improvements in correct artemether-lumefantrine ( AL ) management both immediately after the intervention ( November 2009 ) and 6 months later ( May 2010 ) . In-depth interviews with 24 health workers were undertaken to investigate the possible drivers of this change . The results suggest high acceptance of all components of the intervention , with the active delivery of information in an on the job setting , the ready availability of new and stored text messages and the perception of being kept ‘ up to date ’ as important factors influencing practice . Applying the construct of stages of change we infer that in this intervention the SMS messages were operating primarily at the action and maintenance stages of behaviour change achieving their effect by creating an enabling environment and providing a prompt to action for the implementation of case management practice s that had already been accepted as the clinical norm by the health workers . Future trials testing the effectiveness of SMS reminders in creating an enabling environment for the establishment of new norms in clinical practice as well as in providing a prompt to action for the implementation of the new case-management guidelines are justified Objective : There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy ( ART ) . This study tested the efficacy of short message service ( SMS ) reminders on adherence to ART among patients attending a rural clinic in Kenya . Design : A r and omized controlled trial of four SMS reminder interventions with 48 weeks of follow-up . Methods : Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and r and omly assigned to a control group or one of the four intervention groups . Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency . Adherence was measured using the medication event monitoring system . The primary outcome was whether adherence exceeded 90 % during each 12-week period of analysis and the 48-week study period . The secondary outcome was whether there were treatment interruptions lasting at least 48 h. Results : In intention-to-treat analysis , 53 % of participants receiving weekly SMS reminders achieved adherence of at least 90 % during the 48 weeks of the study , compared with 40 % of participants in the control group ( P = 0.03 ) . Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group ( 81 vs. 90 % , P = 0.03 ) . Conclusion : These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in re source -limited setting INTRODUCTION We will be unable to achieve sustained impact on health outcomes with community health worker (CHW)-based interventions unless we bridge the gap between small scale efficacy studies and large scale interventions . Effective strategies to support the management of CHWs are central to bridging the gap . Mobile phones are broadly available , particularly in low and middle income countries ( LAMIC 's ) , where the penetration rate approaches 100 % . In this article we describe how mobile phones may be combined with mobile web-based technology to assist in the management of CHWs in two projects in South Africa . METHODS This paper is a descriptive one , drawing lessons from two R and omised Controlled Trials ( RCT ' s ) , outlining how a mobile phone information system can be utilized to enhance the quality of health interventions . We organized our comprehensive management and supervision system around a previously published management framework . The system is composed of mobile phones utilized by CHWs and a web-based interface utilized by CHW supervisors . Computerized algorithms were design ed with intervention and assessment protocol s to aid in the real-time supervision and management of CHWs . RESULTS CHWs used mobile phones to initiate intervention visits and trigger content to be delivered during the course of intervention visits . Supervisors used the web-based interface for real-time monitoring of the location , timing , and content of intervention visits . Additional real-time support was provided through direct support calls in the event of crises in the field . CONCLUSION Mobile phone-based information system platforms offer significant opportunities to improve CHW-delivered interventions . The extent to which these efficiency gains can be translated into realized health gains for communities is yet to be tested OBJECTIVE South Africa has one of the highest human immunodeficiency virus ( HIV ) prevalence rates in the world , but despite the well-established benefits of HIV counseling and testing ( HCT ) , there is low uptake of HCT . The study aim ed to investigate the effectiveness of using short message services ( SMSs ) to encourage HCT while interrogating the impact of altering SMS content and dosage ( the number of SMSs ) . MATERIAL S AND METHODS About 2,533 participants were recruited via an SMS sent to 24,000 mobiles r and omly sample d from a pre-existing data base . Recruits were r and omly allocated to four intervention groups that received 3 or 10 informational ( INFO ) or motivational ( MOTI ) SMSs , and a control group . After the intervention , participants were prompted to go for HCT , and postintervention assessment was done after 3 weeks . RESULTS In comparison with the control , receipt of 10 MOTI messages had the most impact on uptake of HCT with a 1.7-fold increased odds of testing ( confidence interval 95 % ; p=0.0036 ) . The lack of efficacy of three SMSs indicates a threshold effect , that is , a minimum number of MOTI SMSs is required . INFO SMSs , whether 3 or 10 were sent , did not have a statistically significant effect . The cost can be calculated for the marginal effect of the SMSs , that is , the cost to get people to test over and above those who were likely to test without the intervention . Use of 10 MOTI SMSs yielded a cost-per-tester of $ 2.41 . CONCLUSIONS While there are method ological issues apparent in our study , the results demonstrate the potential of SMSs to influence the uptake of HCT , the importance of appropriate content , and the need to determine a threshold for SMS-based interventions . These results indicate a potential for SMSs to be used more generally for interventions encouraging people to take health-related actions , and the need for further research in this field . The reasonable cost-per-tester is promising for the scale-up of such an intervention Background Effective use of proven treatments for high blood pressure , a preventable health risk , is challenging for many patients . Prompts via mobile phone SMS-text messaging may improve adherence to clinic visits and treatment , though more research is needed on impact and patient perceptions of such support interventions , especially in low-re source setting s. Method An individually-r and omised controlled trial in a primary care clinic in Cape Town ( 2012–14 ) , tested the effect of an adherence support intervention delivered via SMS-texts , on blood pressure control and adherence to medication , for hypertensive patients . ( Trial registration : Clinical Trials.gov NCT02019823 ) . We report on a qualitative evaluation that explored the trial participants ’ experiences and responses to the SMS-text messages , and identified barriers and facilitators to delivering adherence support via patients ’ own mobile phones . Two focus groups and fifteen individual interviews were conducted . We used comparative and thematic analysis approaches to identify themes and triangulated our analysis amongst three research ers . Results Most participants were comfortable with the technology of using SMS-text messages . Messages were experienced as acceptable , relevant and useful to a broad range of participants . The SMS-content , the respectful tone and the delivery ( timing of reminders and frequency ) and the relational aspect of trial participation ( feeling cared for ) were all highly valued . A subgroup who benefitted the most , were those who had been struggling with adherence due to high levels of personal stress . The intervention appeared to coincide with their readiness for change , and provided practical and emotional support for improving adherence behaviour . Change may have been facilitated through increased acknowledgement of their health status and attitudinal change towards greater self-responsibility . Complex interaction of psycho-social stressors and health service problems were reported as broader challenges to adherence behaviours . Conclusion Adherence support for treatment of raised blood pressure , delivered via SMS-text message on the patient ’s own phone , was found to be acceptable , relevant and helpful , even for those who already had their own reminder systems in place . Our findings begin to identify for whom and what core elements of the SMS-text message intervention appear to work best in a low-re source operational setting , issues that future research should explore in greater depth Background Despite investments in infrastructure and evidence for high acceptability , few mHealth interventions have been implemented in sub-Saharan Africa . Objective We sought to ( 1 ) identify predictors of uptake of an mHealth application for a low-literacy population of people living with HIV ( PLWH ) in rural Ug and a and ( 2 ) evaluate the efficacy of various short message service ( SMS ) text message formats to optimize the balance between confidentiality and accessibility . Methods The trial evaluated the efficacy of a SMS text messaging app to notify PLWH of their laboratory results and request return to care for those with abnormal test results . Participants with a normal laboratory result received a single SMS text message indicating results were normal . Participants with an abnormal test result were r and omized to 1 of 3 message formats design ed to evaluate trade-offs between clarity and privacy : ( 1 ) an SMS text message that stated results were abnormal and requested return to clinic ( “ direct ” ) , ( 2 ) the same message protected by a 4-digit PIN code ( “ PIN ” ) , and ( 3 ) the message “ ABCDEFG ” explained at enrollment to indicate abnormal results ( “ coded ” ) . Outcomes of interest were ( 1 ) self-reported receipt of the SMS text message , ( 2 ) accurate identification of the message , and ( 3 ) return to care within 7 days ( for abnormal results ) or on the date of the scheduled appointment ( for normal results ) . We fit regression models for each outcome with the following explanatory variables : sociodemographic characteristics , CD4 count result , ability to read a complete sentence , ability to access a test message on enrollment , and format of SMS text message . Results Seventy-two percent ( 234/385 ) of participants successfully receiving a message , 87.6 % ( 219/250 ) correctly identified the message format , and 60.8 % ( 234/385 ) returned to clinic at the requested time . Among participants with abnormal tests results ( 138/385 , 35.8 % ) , the strongest predictors of reported message receipt were the ability to read a complete sentence and a demonstrated ability to access a test message on enrollment . Participants with an abnormal result who could read a complete sentence were also more likely to accurately identify the message format ( AOR 4.54 , 95 % CI 1.42 - 14.47 , P=.01 ) and return to clinic appropriately ( AOR 3.81 , 95 % CI 1.61 - 9.03 , P=.002 ) . Those who were sent a PIN-protected message were less likely to identify the message ( AOR 0.11 , 95 % CI 0.03 - 0.44 , P=.002 ) or return within 7 days ( AOR 0.26 , 95 % CI 0.10 - 0.66 , P=.005 ) . Gender , age , and socioeconomic characteristics did not predict any outcomes and there were no differences in outcomes between those receiving direct or coded messages . Conclusions Confirmed literacy at the time of enrollment was a robust predictor of SMS text message receipt , identification , and appropriate response for PLWH in rural Ug and a. PIN-protected messages reduced odds of clinic return , but coded messages were as effective as direct messages and might augment privacy . Trial Registration Clinical trials.gov NCT 01579214 ; https:// clinical trials.gov/ct2/show/NCT01579214 ( Archived by WebCite at http://www.webcitation.org/6Ww8R4sKq ) Mobile phone access in low and middle-income countries is rapidly exp and ing and offers an opportunity to leverage limited human re sources for health . We conducted a mixed methods evaluation of a cluster-r and omized trial exploratory sub study on the impact of a mHealth ( mobile phone ) support intervention used by community-based peer health workers ( PHW ) on AIDS care in rural Ug and a. 29 PHWs at 10 clinics were r and omized by clinic to receive the intervention or not . PHWs used phones to call and text higher level providers with patient-specific clinical information . 970 patients cared for by the PHWs were followed over a 26 month period . No significant differences were found in patients ’ risk of virologic failure . Qualitative analyses found improvements in patient care and logistics and broad support for the mHealth intervention among patients , clinic staff , and PHWs . Key challenges identified included variable patient phone access , privacy concerns , and phone maintenance Background Using two-way mobile phone text messages to improve adherence to antiretroviral medication enhances communication between patients and health workers . We describe the implication s of participants ’ responses to text messages in the Cameroon Mobile Phone SMS ( CAMPS ) trial . Findings This is a cross-sectional analysis of data from the intervention arm of the CAMPS trial . CAMPS was a r and omized controlled trial of motivational text messaging versus usual care to improve adherence to antiretroviral medication among people living with HIV in Yaounde , Cameroon ( n = 200 ) over a 6 month period . Participants in the intervention arm ( n = 101 ) were given a contact phone number , but were not required to respond to their reminder messages . If they did , their responses were noted and reported as counts and percentages . We received 99 phone calls and 55 text messages ( 154 responses ) from 48 participants during the study period . The median number of responses was 1 ( first quartile [ Q1 ] : 1 ; third quartile [ Q3 ] : 3 ) . Half ( n = 79 , 51.1 % ) of them were expressions of gratitude . The rest included requests for logistical ( n = 21 , 13.6 % ) , medical ( n = 20 , 12.9 % ) and financial ( n = 11 , 7.1 % ) support . Conclusion Initiating two-way mobile communication opens more channels for people living with HIV to express unmet needs . Research ers , policy makers and clinicians should be ready to respond to the needs expressed by patients who respond to text messages . Trial registration Pan-African Clinical Trials Registry : PACTR201011000261458 Clinical trials.gov : Background Adequate antenatal care is important to both the health of a pregnant woman and her unborn baby . Given South Africa ’s high rate of cellphone penetration , mobile health interventions have been touted as a potentially powerful means to disseminate health information . This study aim ed to increase antenatal health knowledge and awareness by disseminating text messages about clinic procedures at antenatal visits , and how to be healthy during pregnancy . Methods Participants recruited were pregnant women attending a primary health care facility in Cape Town . A controlled clinical trial was carried out where the intervention group ( n = 102 ) received text messages staggered according to the week of pregnancy at the time of recruitment . The control group ( n = 104 ) received no text messages . These text messages contained antenatal health information , and were delivered in English , Xhosa or Afrikaans , according to the preference of each participant . A baseline knowledge question naire with nine questions was administered prior to the intervention . The same question naire was used with added health-related behaviour questions for the intervention group at exit . A modified intention-to-treat analysis was done . To compare the control and intervention group ’s knowledge , Fisher ’s exact tests and two- sample t-tests tests were carried out for binary and continuous outcomes , respectively . A focus group of seven participants from the intervention group was then conducted to gain more insight into how the text messages were perceived . Results There was substantial loss to follow-up during the study with only 57 % of the participants retained at exit . No statistically significant difference was detected between the control and intervention group in any of the nine knowledge questions at exit ( all p > 0.05 ) . Responses from the focus group indicated that the text messages acted as a welcome reminder and a source of positive motivation , and were perceived as extended care from the health care provider . Conclusions While the intervention failed to improve antenatal health knowledge , evidence from self-reported behaviour and the focus group suggests that text messages have the potential to motivate change in health-seeking behaviour . One should be mindful of loss to follow-up when rolling out mobile health interventions in developing country setting s . Trial registration Pan African Clinical Trials Registry PACTR201406000841188 . Registered 3 June 2014 Summary Background Health workers ' malaria case-management practice s often differ from national guidelines . We assessed whether text-message reminders sent to health workers ' mobile phones could improve and maintain their adherence to treatment guidelines for outpatient paediatric malaria in Kenya . Methods From March 6 , 2009 , to May 31 , 2010 , we did a cluster-r and omised controlled trial at 107 rural health facilities in 11 districts in coastal and western Kenya . With a computer-generated sequence , health facilities were r and omly allocated to either the intervention group , in which all health workers received text messages on their personal mobile phones on malaria case-management for 6 months , or the control group , in which health workers did not receive any text messages . Health workers were not masked to the intervention , although patients were unaware of whether they were in an intervention or control facility . The primary outcome was correct management with artemether-lumefantrine , defined as a dichotomous composite indicator of treatment , dispensing , and counselling tasks concordant with Kenyan national guidelines . The primary analysis was by intention to treat . The trial is registered with Current Controlled Trials , IS RCT N72328636 . Findings 119 health workers received the intervention . Case-management practice s were assessed for 2269 children who needed treatment ( 1157 in the intervention group and 1112 in the control group ) . Intention-to-treat analysis showed that correct artemether-lumefantrine management improved by 23·7 percentage-points ( 95 % CI 7·6–40·0 ; p=0·004 ) immediately after intervention and by 24·5 percentage-points ( 8·1–41·0 ; p=0·003 ) 6 months later . Interpretation In re source -limited setting s , malaria control programmes should consider use of text messaging to improve health workers ' case-management practice s. Funding The Wellcome Trust Oral rehydration solution ( ORS ) and zinc are the recommended treatment in developing countries for the management of uncomplicated diarrhoea in children under five ( World Health Organization and UNICEF 2004 ) . However , drug sellers often recommend costly and unnecessary treatments instead . This article reports findings from an experiment to encourage licensed chemical sellers ( LCS ) in Ghana to recommend ORS and zinc for the management of childhood diarrhoea . The intervention consisted of mobile phone text messages ( Short Message Service or SMS ) sent to a r and omly assigned group of LCS who had been trained on the diarrhoea management protocol s recommended by the World Health Organization ( WHO ) . The SMS campaign comprised informational messages and interactive quizzes sent over an 8-week period . The study measured the impact of the SMS messages on both reported and actual practice s. Analysis of data from both face-to-face interviews and mystery client visits shows that the SMS intervention improved providers ' self-reported practice s but not their actual practice s. The study also finds that actual practice s deviate substantially from reported practice The objective of this study was to assess the acceptability and feasibility of a cell phone based case manager intervention targeting HIV-infected pregnant women on highly-active antiretroviral therapy ( HAART ) . Pregnant women ≥36 weeks gestation attending antenatal care and receiving HAART through the Option B+ program at a primary care clinic in South Africa were enrolled into a prospect i ve pilot intervention to receive text messages and telephone calls from a case manager through 6 weeks postpartum . Acceptability and feasibility of the intervention were assessed along with infant HIV testing rates and 10-week and 12-month postpartum maternal retention in care . Retention outcomes were compared to women of similar eligibility receiving care prior to the intervention . Fifty women were enrolled into the pilot from May to July 2013 . Most ( 70 % ) were HAART-naive at time of conception and started HAART during antenatal care . During the intervention , the case manager sent 482 text messages and completed 202 telephone calls , for a median of 10 text messages and 4 calls/woman . Ninety-six percent completed the postpartum interview and 47/48 ( 98 % ) endorsed the utility of the intervention . Engagement in 10-week postpartum maternal HIV care was > 90 % in the pre-intervention ( n = 50 ) and intervention ( n = 50 ) periods ; by 12-months retention fell to 72 % and was the same across periods . More infants received HIV-testing by 10-weeks in the intervention period as compared to pre-intervention ( 90.0 vs. 63.3 % , p < 0.01 ) . Maternal support through a cell phone based case manager approach was highly acceptable among South African HIV infected women on HAART and feasible , warranting further assessment of effectiveness BACKGROUND Mobile ( cell ) phone communication has been suggested as a method to improve delivery of health services . However , data on the effects of mobile health technology on patient outcomes in re source -limited setting s are limited . We aim ed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load . METHODS WelTel Kenya1 was a multisite r and omised clinical trial of HIV-infected adults initiating antiretroviral therapy ( ART ) in three clinics in Kenya . Patients were r and omised ( 1:1 ) by simple r and omisation with a r and om number generating program to a mobile phone short message service ( SMS ) intervention or st and ard care . Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. R and omisation , laboratory assays , and analyses were done by investigators masked to treatment allocation ; however , study participants and clinic staff were not masked to treatment . Primary outcomes were self-reported ART adherence ( > 95 % of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits ) and plasma HIV-1 viral RNA load suppression ( < 400 copies per mL ) at 12 months . The primary analysis was by intention to treat . This trial is registered with Clinical Trials.gov , NCT00830622 . FINDINGS Between May , 2007 , and October , 2008 , we r and omly assigned 538 participants to the SMS intervention ( n=273 ) or to st and ard care ( n=265 ) . Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group ( relative risk [ RR ] for non-adherence 0·81 , 95 % CI 0·69 - 0·94 ; p=0·006 ) . Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group , ( RR for virologic failure 0·84 , 95 % CI 0·71 - 0·99 ; p=0·04 ) . The number needed to treat ( NNT ) to achieve greater than 95 % adherence was nine ( 95 % CI 5·0 - 29·5 ) and the NNT to achieve viral load suppression was 11 ( 5·8 - 227·3 ) . INTERPRETATION Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals . Mobile phones might be effective tools to improve patient outcome in re source -limited setting s. FUNDING US President 's Emergency Plan for AIDS Relief Objective : Many sub-Saharan African countries report high postpartum loss to follow-up of mother – baby pairs . We aim ed to determine whether interactive text messages improved rates of clinic attendance and early infant HIV testing in the Nyanza region of Kenya . Design : Parallel-group , unblinded , r and omized controlled trial . Methods : HIV-positive pregnant women at least 18 years old and enrolled in the prevention of mother-to-child transmission of HIV programme were r and omized to receive either text messages ( SMS group , n = 195 ) or usual care ( n = 193 ) . Messages were developed using formative focus group research informed by constructs of the Health Belief Model . The SMS group received up to eight text messages before delivery ( depending on gestational age ) , and six messages postpartum . Primary outcomes included maternal postpartum clinic attendance and virological infant HIV testing by 8 weeks postpartum . The primary analyses were intention-to-treat . Results : Of the 388 enrolled women , 381 ( 98.2 % ) had final outcome information . In the SMS group , 38 of 194 ( 19.6 % ) women attended a maternal postpartum clinic compared to 22 of 187 ( 11.8 % ) in the control group ( relative risk 1.66 , 95 % confidence interval 1.02–2.70 ) . HIV testing within 8 weeks was performed in 172 of 187 ( 92.0 % ) infants in the SMS group compared to 154 of 181 ( 85.1 % ) in the control group ( relative risk 1.08 , 95 % confidence interval 1.00–1.16 ) . Conclusions : Text messaging significantly improved maternal postpartum visit attendance , but overall return rates for these visits remained low . In contrast , high rates of early infant HIV testing were achieved in both arms , with significantly higher testing rates in the SMS compared to the control infants Background Medical abortion is legal in South Africa but access and acceptability are hampered by the current protocol requiring a follow-up visit to assess abortion completion . Objective To assess the feasibility and efficacy of information and follow-up provided via mobile phone after medical abortion in a r and omized controlled trial ( RCT ) . Methods Mobile phones were used in three ways in the study : ( 1 ) coaching women through medical abortion using short message service ( SMS ; text messages ) ; ( 2 ) a question naire to assess abortion completion via unstructured supplementary service data ( USSD , a protocol used by GSM mobile telephones that allows the user to interact with a server via text-based menus ) and the South African mobile instant message and social networking application Mxit ; and ( 3 ) family planning information via SMS , mobisite and Mxit . A needs and context assessment was done to learn about women ’s experiences undergoing medical abortion and their use of mobile phones . After development , the mobile interventions were piloted . Recruitment was done by field workers at the clinics . In the RCT , women were interviewed at baseline and exit . Computer logs were also analyzed . All study participants received st and ard of care at the clinics . Results In the RCT , 234 women were r and omized to the intervention group . Eight did not receive the intervention due to invalid numbers , mis- registration , system failure , or opt-out , leaving 226 participants receiving the full intervention . Of the 226 , 190 returned and were interviewed at their clinic follow-up visit . The SMSs were highly acceptable , with 97.9 % ( 186/190 ) saying that the SMSs helped them through the medical abortion . In terms of mobile phone privacy , 86.3 % ( 202/234 ) said that it was not likely or possible that someone would see SMSs on their phone , although at exit , 20 % ( 38/190 ) indicated that they had worried about phone privacy . Having been given training at baseline and subsequently asked via SMS to complete the self- assessment question naire , 90.3 % ( 204/226 ) attempted it , and of those , 86.3 % ( 176/204 ) reached an endpoint of the question naire . For the family planning information , a preference for SMS was indicated by study clients , although the publicly available Mxit/mobisite was heavily used ( 813,375 pages were viewed ) over the study duration . Conclusions SMS provided a good medium for timed , " push " information that guided and supported women through medical abortion . Women were able to perform a self- assessment question naire via mobile phones if provided training and prompted by SMS . Phone privacy needs to be protected in similar setting s. This study may contribute to the successful expansion of medical abortion provision aided by mobile phones . Trial Registration Pan African Clinical Trials Registry ( PACTR ) : PACTR201302000427144 ; http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?dar=true&tNo=PACTR201302000427144 ( Archived by WebCite at http://www.webcitation.org/6N0fnZfzm ) Please cite this paper as : Lund S , Hemed M , Nielsen B , Said A , Said K , Makungu M , Rasch V. Mobile phones as a health communication tool to improve skilled attendance at delivery in Zanzibar : a cluster‐r and omised controlled trial . BJOG 2012;119:1256–1264 OBJECTIVE Poor adherence to medications , including psychotropic medications contributes to the burden of disease . Mental health service users ( MHSU ) may also not attend follow-up appointments at their health care facilities where they could discuss adherence with their health care provider . This paper reports on preliminary qualitative research preceding a r and omised controlled trial that aims to improve adherence to psychotropic medication and to follow up treatment visits . The intervention will entail the support of individuals with serious mental disorder by a treatment partner and short message service ( SMS ) text messaging . METHODS The preliminary research reported in this paper aim ed to extract views about the intervention from both mental health service users ( MHSU ) and caregivers through focus group discussion s and individual interviews . Data were analysed using ATLAS TI qualitative software . RESULTS The caregivers interviewed were all mothers of MHSU who took measures to encourage adherence . They held mixed opinions on whether the treatment partner should be a family member . Most participants expressed the view that due to living conditions , family members were natural treatment partners , but others stated that they would prefer a treatment partner who was not a family member . Similarly , while most MHSU supported the idea of a treatment partner , a minority were concerned that a treatment partner may potentially be too controlling and compromise their autonomy . The vast majority of participants supported SMS text messaging as a means of reminding MHSU to take their medication and attend follow-up appointments . One participant mentioned the importance of broader social inclusion issues that should be incorporated in the intervention . CONCLUSION Qualitative research may provide useful insights for the design of interventions of this nature related to social inclusion r and omised control trials with its focus on adherence Many people newly diagnosed with HIV are lost to follow-up before timely initiation of antiretroviral therapy ( ART ) . A r and omised controlled trial ( RCT ) , WelTel Kenya1 , demonstrated the effectiveness of the WelTel text messaging intervention to improve clinical outcomes among patients initiating ART . In preparation for WelTel Retain , an RCT that will evaluate the effect of the intervention to retain patients in care immediately following HIV diagnosis , we conducted an informative qualitative study with people living with HIV ( n = 15 ) and healthcare providers ( HCP ) ( n = 5 ) in October 2012 . Study objectives included exploring the experiences of people living with HIV who have attempted to engage in HIV care , the use of cell phones in everyday life , and perceptions of communicating via text message with HCP . Participants were recruited through convenience sampling . Semi-structured , qualitative interviews were conducted and recorded , transcribed verbatim and analysed using NVivo software . Analysis was guided by the Theory of Reasoned Action and the Technology Acceptance Model . Results indicate that while individuals have many motivators for engaging in care after diagnosis , structural and individual barriers including poverty , depression and fear of stigma prevent them from doing so . All participants had access to a mobile phone , and most were comfortable communicating through text messages , or were willing to learn . Both people living with HIV and HCP felt that increased communication via the text messaging intervention has the potential to enable early identification of problems , leading to timely problem solving that may improve retention and engagement in care during the first year after diagnosis OBJECTIVES Home use of misoprostol for medical abortion is more convenient for many women than in-clinic use but requires management of abortion symptoms at home without provider backup . This study evaluated whether automated text messages to women undergoing medical abortion can reduce anxiety and emotional discomfort , and whether the messages can better prepare women for symptoms they experience . STUDY DESIGN A multisite r and omized controlled trial was conducted in which women undergoing early medical abortion were allocated to receive st and ard of care ( SOC ) only ( n=235 ) or SOC+a messaging intervention ( n=234 ) . Consenting women were interviewed at the clinic after taking mifepristone and again at their follow-up clinic visit 2 - 3 weeks later ; the intervention group received text messages over the duration of this period . Emotional outcomes were evaluated using the Hospital Anxiety and Depression Scale , Adler 's 12-item emotional scale and the Impact of Event Scale-Revised . Preparedness for the abortion symptoms and overall satisfaction with the procedure were assessed using 4-point Likert-type scales . RESULTS Between baseline and follow-up , anxiety decreased more ( p=0.013 ) , and less emotional stress was experienced ( adjusted for baseline anxiety , p=0.015 ) , in the intervention compared to the SOC group . Participants in the intervention group were also more likely to report that they felt very well prepared for the bleeding ( p<0.001 ) , pain ( p=0.042 ) and side effects ( p=0.027 ) they experienced . Acceptability and other negative emotions relating to the abortion did not differ between study groups . Ninety-nine percent of the intervention group stated that they would recommend the messages to a friend having the same procedure . CONCLUSIONS Text messages to women following mifepristone administration for early medical abortion may assist them in managing symptoms and appear highly acceptable to recipients . IMPLICATION STATEMENT This r and omized controlled trial provides evidence for the effectiveness of text messages following mifepristone administration in strengthening medical abortion care . The messages were associated with significant reductions in women 's anxiety and stress during the abortion process ; they improved preparedness for the abortion symptoms experienced and appeared highly acceptable |
12,428 | 30,387,864 | The overall risk difference for CH versus adhesive system in primary teeth was 0.06 [ 95 % CI -0.01 to 0.13 ] , and the overall risk difference for CH versus GIC was 0.10 [ 95 % CI -0.01 to 0.22 ] , with no significant differences between material s. CH liner did not influence the clinical success of treatment for deep caries lesions of primary or permanent teeth . | The aim of this systematic review and meta- analysis was to evaluate whether the use of calcium hydroxide ( CH ) liner improves the clinical success in the treatment of deep caries lesions of primary and permanent teeth . | Concern about the survival of microorganisms in deep carious lesions may often lead to unnecessary exposure of the pulp during final excavation . There are reasons , therefore , to initiate systematic studies on the alternative procedure known as stepwise excavation . Clinical evaluation of stepwise excavation was performed on 31 deep carious lesions considered to result in pulp perforation by traditional excavation . This study examines the clinical and microbiological alterations during the final excavation performed during long intervals ( 6 - 12 months ) after the initial treatment that included peripheral dentine excavation and removal of the central cariogenic biomass and the superficial necrotic dentine . The dentine colour and consistency were assessed by means of st and ardized scales before application of a Ca(OH)2 compound and a temporary sealing for 6 - 12 months . Re assessment s were performed before the after final excavation . Microbiological dentine sample s were obtained in 19 r and omly selected lesions by a sterile bur , transferred to and diluted in reduced transport fluid , and plated on tryptic soy agar . After anaerobic incubation at 37 degrees C for 7 days , total colony-forming units per millilitre were counted from ( 1 ) peripheral excavated and hard dentine ( control ) , ( 2 ) central demineralized dentine before and final excavation , and ( 3 ) central dentine after the final excavation . Six sample s of central demineralized dentine were without any cultivable flora increasing to 9 sample s after the final excavation . The clinical dentine changes occurring during stepwise excavation were characterized by enhanced hardness of the dentine which was associated with a marked reduction in bacterial growth after the final excavation . Despite the presence of bacteria in the excavated dentine none of the carious lesions result ed in pulp perforation , suggesting that the initial removal of the cariogenic biomass appears to be essential for control of caries progression . Stepwise excavation is not only an appropriate treatment of deep carious lesions but is also considered a suitable model for microbiological studies to determine the bacteria persisting in clinical ly excavated lesions Objective This multicenter r and omized controlled clinical trial aim ed to compare the outcomes of stepwise excavation ( SW ) and partial caries removal ( PCR ) regarding the maintenance of pulp vitality in deep caries lesions over 5 years . Methods At baseline , 299 permanent molars with deep caries lesions were r and omly assigned to control or test groups . The control group received the stepwise excavation treatment ( SW ) , while the test group received partial caries removal from the pulpal wall followed by restoration in a single session ( PCR ) . Treatments were conducted in two centers located in the cities of Porto Alegre ( South Brazil ) and Brasília ( Midwest Brazil ) . Survival analysis was performed to compare PCR and SW over time ( Weibull regression models ) . The primary outcome of this study was pulp vitality , determined by the combination of the following characteristics : positive response to cold test , negative response to percussion , absence of spontaneous pain , and absence of periapical lesion ( radiographic examination ) . Results This 5-year study includes data pertaining to 229 teeth : 121 teeth actually examined at the 5-year appointment , and 108 teeth contributed with data collected in previous follow-ups ( 18 months or 3 years ) . Survival analysis showed success rates of 80 % in PCR group and 56 % in SW group ( p < 0.001 ) . Failure was significantly associated with treatment [ PCR , HR=0.38 ; 95%CI=0.23–0.63 ) ] and region [ South , HR=2.22 ; 95%CI=1.21–4.08 ] . Conclusion PCR significantly reduced the occurrence of pulp necrosis when compared with SW . Clinical relevance This study supports the PCR as a single-visit technique to manage deep caries lesions in permanent teeth OBJECTIVE To evaluate the clinical and radiographic outcomes ( 24 months ) of indirect pulp treatment ( IPT ) in primary teeth when a self-etching primer or a calcium hydroxide layer was used over the remaining carious dentin . STUDY DESIGN Primary molar teeth with deep carious lesions without signs and symptoms of irreversible pulpitis were divided into two groups , according to the capping material : Experimental group ( 1 ) : self-etching adhesive system ( Clearfill SE Bond ) ; and Control group ( 2 ) : calcium hydroxide liner ( Dycal ) . Both groups were followed up after application of a resin restoration ( 3 M - Z250 ) . RESULTS After 2 years of clinical and radiographic follow-up , no statistical difference was found between groups ( p = 1 ) . The overall success rate reached 87 % . CONCLUSION These results demonstrate that IPT has a high clinical and radiographic performance in primary teeth and is not dependent on the capping material used over the demineralized dentin PURPOSE The purpose of this study was to investigate dentin rehardening in the remaining carious dentin after indirect pulp treatment ( IPT ) using microhardness analysis after 37 to 71 months . METHODS Eighteen teeth su bmi tted to IPT and capped with calcium hydroxide ( CH ) or gutta-percha ( GP ) were evaluated ( treated group ) . Ten sound molars and 10 molars with deep acute carious lesions were selected to serve as positive and negative control groups , respectively . In the treated group , restorations and pulp-capping material s were removed . In the positive control group , 3- to 4-mm deep cavities were prepared . In the negative control group , the carious tissue was removed . Microhardness analysis was performed at 10- , 35- , 60- , 85- , and 110-microm depths . Data were analyzed using 1-way analysis of variance ( P<.05 ) . RESULTS Microhardness values for sound , carious , and treated groups at 10- , 35- , 60- , 85- , and 110-microm depths showed a statistically significant difference ( P < or=.01 ) among the groups for microhardness . No difference was observed between CH- and GP-treated groups for microhardness . CONCLUSION The results showed a hardness increase in treated teeth when compared to carious teeth in all dentin depths investigated , suggesting mineral gain after treatment PURPOSE The purpose of this study was to evaluate the effect of the material s used for indirect pulp treatment ( IPT ) on the long-term outcome of primary molar teeth . METHODS Forty-eight teeth with deep carious lesions , but without signs and symptoms of irreversible pulpitis , were r and omly divided into 2 groups , according to the material placed on the demineralized dentin remain : ( 1 ) experimental group , adhesive system ( Scotchbond Multi purpose ) ; and ( 2 ) control group , calcium hydroxide liner ( Dycal ) . Both groups were followed by a resin restoration application . RESULTS After 4 to 5 years , the clinical and radiographic success rates between groups were similar ( group 1=14 of 15 ; group 2=8 of 10 ; P=0.350 ) . Subsequent to exfoliation , scanning electron microscopy revealed the presence of a hybrid layer at the resin-dentin interface and a microtensile bond strength of 9.63 MPa ( group 1 ) . Histological analysis showed that the pulp health status was similar in both groups . CONCLUSIONS Indirect pulp treatment has a high clinical and radiographic long-term success rate in primary teeth and is not material -dependent PURPOSE The purpose of this prospect i ve and r and omized in vivo study was to compare the clinical and radiographic outcomes of an adhesive resin system vs a calcium hydroxide liner for protection of the dentin-pulp complex of primary molars treated with indirect pulp treatment . METHODS Forty-eight primary molars with deep occlusal caries , but without preoperative signs and symptoms of irreversible pulpitis , received indirect pulp treatment and were restored with a composite resin ( Z100 ) . The teeth were r and omly divided into 2 groups according to the material used for protection of the dentin-pulp complex : ( 1 ) adhesive resin system ( Scotchbond Multi Purpose ) ; and ( 2 ) calcium hydroxide liner ( Dycal ) . These teeth were evaluated clinical ly and radiographicaly for 2 years . RESULTS After 2 years , 83 % ( 19/23 ) of the teeth treated with calcium hydroxide and 96 % ( 24/25 ) of teeth treated with only the adhesive resin system presented a successful outcome , as determined by clinical and radiographic examination . Interradicular and /or periapical lesions were the most predominant signs of treatment failure , since 3 out of 23 teeth treated with calcium hydroxide and 1 out of 25 teeth treated with only adhesive resin presented this outcome . One tooth treated with the calcium hydroxide liner was diagnosed with internal root resorption at the 18-month examination . Of the 5 teeth diagnosed from radiographs as a failure of the indirect pulp treatment , none presented clinical signs/symptoms of pulpitis or necrosis such as the presence of fistula , enhanced tooth mobility , or pain . CONCLUSIONS This study demonstrates that protection of the dentin-pulp complex of primary molars with an adhesive resin system results in similar clinical and radiographic 2-year outcomes as compared to calcium hydroxide when indirect pulp treatment is performed in Class I composite restorations With the purpose of checking , in vivo , the effect of atraumatic restorative treatment ( ART ) on the remaining demineralized dentin , 12 primary molars with deep occlusal lesions from children with ages ranging from 3 to 7 were evaluated . After lesion excavation , and before glass ionomer cement placement , dentin sample s were collected from the pulpal wall of the cavity . After 3 months , the restorations were removed and new sample s were collected . Six micro areas of each sample were analyzed by X-ray energy dispersion spectrometer . Sample s obtained before treatment were infected and intertubular dentin had a loosely organized collagen matrix , with well-defined collagen fibers . Following treatment , in addition to a drastic reduction of the amount of bacteria , the intertubular dentin was denser , with more compact and closely packed collagen fibers . An increased calcium concentration was observed in dentin collected after treatment ( p < 0.001 ) , suggesting tissue remineralization , but fluoride was not detected . We conclude that ART allows a one-session approach , with the purpose of creating more favorable conditions for the healing process PURPOSE To evaluate the clinical and radiographic changes in primary teeth su bmi tted to indirect pulp treatment ( IPT ) over a 36-month period . METHODS Thirty-nine primary molars with deep caries , but without preoperative signs and symptoms of irreversible pulpits , received IPT . The teeth were r and omly divided into two groups , according to the material used for protection of the dentin-pulp complex : ( 1 ) a calcium hydroxide liner ( Hydro C ) and ( 2 ) a gutta-percha sheet . Both groups were restored with Z250 resin-based composite . RESULTS After 36 months , Group 1 showed a success rate of 73.3 % and Group 2 , 85.7 % . The overall success rate was 79.3 % , with no statistically significant difference between the groups ( P = 0.36 ) The aim of this r and omized , controlled , single-blind and prospect i ve study was to evaluate the clinical and radiographic success rates of three different bonding protocol s vs calcium hydroxide liner for protection of the dentin – pulp complex of primary molars with different remaining dentin thicknesses . Two hundred forty primary molar teeth with moderate to deep occlusal caries were restored in 97 children who met inclusion criteria . After cavity preparation , the teeth were r and omly assigned into four groups ( n = 60/group ) with respect to the material used for protection of the dentin – pulp complex : ( 1 ) total-etching with 36 % phosphoric acid followed by an acetone-based adhesive ( Prime&Bond NT ) , ( 2 ) a self-etch adhesive system ( Xeno III ) , ( 3 ) an acetone-based adhesive ( Prime&Bond NT ) without prior acid conditioning , and ( 4 ) control : calcium hydroxide cement ( Dycal ) . Teeth in groups 1–3 were restored with a polyacid-modified resin-based composite ( Dyract AP ) and those in group 4 with amalgam . The remaining dentin thickness was calculated using image analysis software ( ImageJ ) . The teeth were evaluated clinical ly and radiographically for 24 months . The distribution of restored teeth with minimal remaining dentin thickness ( ≤0.5 mm ) was 3.3 , 8.3 , 8.3 , and 10 % for groups 1 , 2 , 3 , and 4 , respectively . Despite the absence of pulpal protection in groups 1–3 , none of those teeth exhibited any significant clinical or radiographic symptom during the study period . After 2 years , the clinical and radiographic success rate of restorative treatments was 100 % . Protection of the dentin – pulp complex with the tested bonding protocol s result ed in similar outcomes in mainly shallow and medium deep cavities as compared to calcium hydroxide amalgam in more deep cavities , when indirect pulp treatment was performed in class I compomer restorations This r and omized , multicenter clinical trial evaluated the effectiveness of 2 treatments for deep caries lesions — partial caries removal ( PCR ) and stepwise excavation ( SW ) — with respect to the primary outcome of pulp vitality for a 3-year follow-up period . Inclusion criteria were as follows : patients with permanent molars presenting deep caries lesions ( lesion affecting ≥ 1/2 of the dentin on radiographic examination ) , positive response to a cold test , absence of spontaneous pain , negative sensitivity to percussion , and absence of periapical lesions ( radiographic examination ) . Teeth r and omly assigned to PCR ( test ) received incomplete caries removal and filling in a single session . Outcome success was evaluated by assessment of pulp vitality , determined by pulp sensitivity to a cold test and the absence of periapical lesions . Data were analyzed by a Weibull regression model with shared frailty term ( survival analysis ) . At baseline , 299 treatments were executed : PCR , 152 and SW , 147 . By the end of the 3-year follow-up period , 213 teeth had been evaluated . Adjusted survival rates were 91 % for PCR and 69 % for SW ( p = 0.004 ) . These results suggest that there is no need to re-open a cavity and perform a second excavation for pulp vitality to be preserved ( Clinical trials registration NCT00887952 ) AIM To test the hypothesis that dentine and pulp protection by conditioning- and -sealing is no less effective than using a conventional calcium hydroxide lining . METHODOLOGY A cohort of healthy adults requiring a new or replacement restoration in a posterior tooth was recruited in six general practice s. All procedures received local Ethics Committee approval . Exclusion criteria included signs and symptoms of pulp necrosis or inflammation , and patients unable to commit to a long-term trial . Cavity preparations were r and omized to receive a calcium hydroxide lining or conditioning- and -sealing with a smear-removing bonding system . Choice of bulk restorative material ( composite resin or amalgam ) was at the discretion of the dentist . The key outcome measure was evidence of pulpal breakdown identified at unscheduled ( emergency ) or scheduled recall examinations . Postoperative sensitivity was recorded on 100 mm VAS at 24 h , 4 days and 7 days . Pulp status was assessed at 6 , 12 , 24 and 36 month recall , and at any emergency recall appointment . The relationship between pre-treatment and treatment variables and pulp breakdown was assessed by logistic regression ( P = 0.05 ) . RESULTS A total of 602 teeth were recruited , with comparable numbers of cavities lined ( 288 , 47.8 % ) or conditioned and sealed ( 314 , 52.2 % ) . The majority ( 492 , 81.7 % ) were replacement restorations , and amalgam was the most common bulk restorative material ( 377 , 62.6 % ) . A total of 390 ( 64.8 % ) restored teeth were review ed at 6 months , 307 ( 51 % ) at 12 months , 363 ( 60.3 % ) at 24 months , and 279 ( 46.3 % ) at 36 months post-restoration . Sixteen cases of pulp breakdown were identified within 36 months of restoration placement , 11 presenting as emergencies and five detected at routine recall examination . Logistic regression showed that preoperative pain , cavity treatment by lining or conditioning- and -sealing and the use of rubber dam isolation had no association with pulp breakdown . Pulp breakdown was associated with deep or pulpally exposed cavities ( P < 0.001 , odds ratio 7.8 ) and with composite rather than amalgam restorations ( P = 0.001 , odds ratio 2.13 ) . Re-coding to identify teeth with pulp exposures revealed that pulpal exposure was the key determinant of adverse pulp outcomes ( P < 0.0001 , odds ratio 28.4 ) and that composite resin restorations were again more likely to be associated with pulp breakdown than amalgam ( P = 0.017 , odds ratio 3.92 ) . CONCLUSIONS Considered within the context of routine primary dental care : Dentists can be confident that pulps will be equally well protected from post-restorative breakdown up to 36 months by calcium hydroxide lining and conditioning- and -sealing with adhesive resins . Residual dentine thickness appears to be a key determinant of pulp responses after restorative dental treatment . In deep and pulpally exposed cavities in posterior teeth , composites were associated with more pulpal breakdown than amalgams Objective : The objective of this study was to determine the most suitable material for indirect pulp treatment ( IPT ) clinical ly and to determine the thickness ( in mm ) and type of tissue in terms of radiodensity ( in Hounsfield units [ HU ] ) formed after pulp capping using cone-beam computed tomography ( CBCT ) scan . Material s and Methods : A longitudinal interventional single-blind r and omized clinical trial was conducted on 94 children ( 7–12 years ) with a deep carious lesion in one or more primary second molar and permanent first molar without the history of spontaneous pain indicated for indirect pulp capping ( IPC ) procedure . About 109 teeth were treated using three material s , namely , calcium hydroxide ( setting type ) , glass ionomer cement ( Type VII ) , and mineral trioxide aggregate r and omly . The teeth were followed up at an interval of 8 weeks , 6 months , and 1 year for success of IPT as per the American Academy of Pediatric Dentistry clinical criteria . For determining the thickness and type of dentin tissue formed , a CBCT scan was done immediately postoperative and another scan at an interval of 6 months . The scans were compared to evaluate the average thickness of the dentin bridge formed . Results and Conclusions : Success rate for IPC was 96.85 % . A significant difference was obtained in the average thickness of reparative dentin at immediate postoperative and 6-month postoperative values in all three groups suggesting distinct barrier formation . Similar significant findings were obtained in radiodensity of barrier formed ( in HU ) . All three material s were found to be equally suitable as IPC agents suggesting mineral gain PURPOSE To evaluate clinical and radiographic outcomes of indirect pulp treatment ( IPT ) in primary molars after long-term function ( up to 60 months ) . METHODS Teeth with deep carious lesions without signs and symptoms of irreversible pulpitis were divided by r and om allocation into two groups , according to the capping material utilized over demineralized dentin : experimental group ( 1 ) : self-etching adhesive system ( Clearfil SE Bond ) ; and control group ( 2 ) : calcium hydroxide liner ( Dycal ) . Both groups were filled with resin composite ( Z250 ) and su bmi tted to a clinical and radiographic monitoring period until exfoliation . RESULTS After the follow-up period ( up to 60 months ) , no statistical difference was found between groups ( P= 0.514 ) . The overall success rate reached 78 % . The failures occurred after the first year period recall PURPOSE Evaluate clinical and radiographic changes in primary teeth su bmi tted to indirect pulp capping ( IPC ) over a 48-month-period . METHODS Twenty seven primary molars with deep caries , but without preoperative signs of irreversible pulpits , were treated with IPC . The teeth were r and omly divided into two groups , according to the material used for protection of the dentin-pulp complex . ( 1 ) a calcium hydroxide liner ( Dycal ) and ( 2 ) glass ionomer cement ( Vitremer ) . RESULTS After 48 months , Group-1 showed a success rate of 88.8 % and Group-2 of 93 % . No statistical significant difference between the groups was observed ( P = 0.62 ) . CLINICAL SIGNIFICANCE The results of this study suggested that indirect pulp capping in primary teeth arrests the progression of the underlying caries , regardless of the material used as a liner Aim : To compare 24-month pulp health outcomes of partial caries removal ( PCR ) and total caries removal ( TCR ) with composite restoration in primary molars . Methods : 48 children aged 3 - 8 years with at least one molar with a deep carious lesion were included . 120 teeth were r and omized to control ( TCR ; n = 54 ; 69 % class II ) and test ( PCR ; n = 66 ; 63 % class II ) groups . Total absence of carious tissue was confirmed using a blunt-tipped probe in the TCR group . For PCR , excavation was stopped when hardened , dried dentin with a leathery consistency was achieved . Pulpotomy was performed in cases of pulp exposure . Results : Pulp exposure occurred in 2 and 27.5 % of teeth treated with PCR and TCR , respectively ( p < 0.01 ) . The operative time was significantly higher for TCR than PCR . Success rates were 92 and 96 % in the PCR and TCR groups , respectively ( p = 0.34 ) . The success rate tended to be lower in occlusoproximal ( 92 % ) than in occlusal ( 100 % ) lesions ( p = 0.08 ) . Conclusion : The clinical and radiographic success rates of PCR and TCR in primary teeth with deep carious lesions were high and did not differ significantly , indicating that PCR is a reliable minimally invasive approach in primary teeth and that the retention of carious dentin does not interfere with pulp vitality . Moreover , PCR provided other clinical ly relevant advantages over TCR , especially lower incidence of pulp exposure and lower operative time PURPOSE To compare the effect of incomplete caries removal ( ICR ) and indirect pulp capping ( IPC ) with calcium hydroxide ( CH ) or an inert material ( wax ) on color , consistency and contamination of the remaining dentin of primary molars . METHODS This double-blind , parallel- design , r and omized controlled trial included 30 children presenting one primary molar with deep caries lesion . Children were r and omly assigned after ICR to receive IPC with CH or wax . All teeth were then restored with resin composite . Baseline dentin color and consistency were evaluated after ICR , and dentin sample s were collected for contamination analyses using scanning electron microscopy . After 3 months , restorations were removed and the three parameters were re-evaluated . In both groups , dentin became significantly darker after 3 months . RESULTS No cases of yellow dentin were observed after 3 months with CH compared to 33.3 % of the wax cases ( P < 0.05 ) . A statistically significant difference over time was observed only for CH regarding consistency . CH stimulated a dentin hardening process in a statistically higher number of cases than wax ( 86.7 % vs. 33.3 % ; P = 0.008 ) . Contamination changed significantly over time in CH and wax without significant difference between groups . It was concluded that CH and wax arrested the carious process of the remaining carious dentin after indirect pulp capping , but CH showed superior dentin color and consistency after 3 months BACKGROUND Clinicians often use calcium hydroxide liners during stepwise treatment of advanced caries . In this r and omized clinical trial , the authors compared the short-term outcome of stepwise caries removal with and without use of a calcium hydroxide liner in conjunction with provisional resin-modified glass ionomer ( RMGI ) restorations . METHODS The authors included in the trial 98 patients aged 15 to 30 years who had a deep carious lesion in a posterior tooth . The authors measured the dentin thickness radiographically and recorded its color , consistency , and moisture , as well as the bacterial count of the lesions . After partial caries removal , the authors assigned patients r and omly to have their caries provisionally restored using RMGI with ( control group ) or without ( test group ) a calcium hydroxide liner . The primary outcome measure was tooth vitality after 90 days . Secondary outcomes included changes in dentinal , radiographic , and microbiological characteristics of the lesions . RESULTS The authors found no statistically significant difference between the test and control groups in tooth vitality after 90 days . Irrespective of calcium hydroxide liner use , the authors observed darker , harder , drier , and less contaminated dentin after the provisional restorations , but dentin thickness remained unchanged . CONCLUSIONS On the basis of this 3-month clinical trial 's results , the use of a calcium hydroxide liner during stepwise caries excavation and provisional restoration did not provide any additional benefit . PRACTICAL IMPLICATION S After 3 months , using a calcium hydroxide liner does not appear to offer any additional benefit when clinicians use RMGI provisional restorations during stepwise caries removal . Longer studies are needed to confirm these results |
12,429 | 24,307,460 | Considering the lack of clinical benefit , there is currently no evidence to recommend or refute antiviral treatment for recurrent liver graft infection with hepatitis C virus . | BACKGROUND Antiviral therapy for recurrent hepatitis C infection after liver transplantation is controversial due to unresolved balance between benefits and harms .
OBJECTIVES To compare the therapeutic benefits and harms of different antiviral regimens in patients with hepatitis C re-infected grafts after liver transplantation . | BACKGROUND S/ AIMS We evaluated the effect of antiviral therapy on fibrosis progression in patients with histological features of mild/moderate HCV disease recurrence defined by a Grading score≥4 and Staging score up to 3 ( Ishak ) at 1 year after liver transplantation . METHODS Seventy-three consecutive patients with mild/moderate recurrence were r and omized either to no treatment or to receive Pegilated-Interferon-alfa-2b and ribavirin for 52 weeks . Liver biopsies obtained at baseline ( 1 year after transplantation ) and 2 years afterwards were evaluated for assessment of disease progression , defined as worsening of at least 2 staging points or progression to stage 4 or higher . RESULTS As for these two major histological end points there were no statistically significant differences between the 2 groups ( 36.1 % vs. 50 % , p=0.34 and 36.1 % vs. 38.9 % , p=1 ) . Fifteen treated patients ( 41 % ) achieved a sustained virological response which was associated with a reduced risk of fibrosis worsening for both endpoints when compared to viremic patients ( p=0.04 ) . CONCLUSIONS Although antiviral-therapy was beneficial in preventing fibrosis progression in patients achieving a sustained virological response , the majority of the overall population of our patients with mild-moderate disease recurrence could not benefit from antiviral therapy either because they either could not be treated or did not respond to treatment ( EudraCT number : 2005 - 005760 ) Background . In this article , we explore the virological response to two types of interferon based treatment in recurrent hepatitis C virus in liver recipients who received thymoglobulin induction . Methods . Fifty consecutive patients were r and omized to receive PEG interferon alpha 2b ( 1.0 & mgr;g/kg per week ) , ribavirin ( 800 mg/d ) plus amantadine ( 200 mg/d ) , or PEG interferon alpha 2b ( 1.0 & mgr;g/kg per week ) plus ribavirin ( 800 mg/d ) . The primary endpoint was absence of hepatitis C virus RNA 6 months posttreatment . The secondary endpoint was change in fibrosis at 1 year . Results . Only 30 patients completed 1 year of treatment . In an intention to treat analysis , the sustained virological response ( SVR ) rate was 26 % in I/R/A group and 50 % in I/R group . By per protocol , the overall SVR rate was 57 % . Fibrosis progression by at least one stage was noted in 37 % patients . Twenty-nine percent of patients who achieved SVR had shown fibrosis progression by at least one stage whereas 46 % nonresponders showed fibrosis progression ( P = NS ) . Conclusion . This is the first study exploring the efficacy of pegylated interferon-based antiviral treatment in patients who received a steroid-free protocol . Our data is encouraging and shows that if liver transplant recipients can tolerate treatment for 1 year there is a reasonable chance of SVR OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials The aim of the study was to observe the frequency of neutropenia during Pegylated Interferon/Ribavirin therapy in patient with chronic hepatitis C ; to compare the efficacy of two strategies of management of neutropenia -- with Interferon dose modification and with Neupogen administration ; to compare the effectiveness rate of sustained viral response ( SVR ) in patients with Pegylated Interferon dose modification and in patients treated by using granulocyte colony-stimulating factor G-CSF-filgrastim . ( Neupogen ) . Study enrolled 47 patients with chronic active hepatitis C , aged 23 - 64 . ( 38 male and 9 female ) . All patients had HCV genotype 1b . Significant neurtopenia ( ANC<750 mm3 ) and severe neurtopenia ( ANC<500 mm3 ) developed in 41 of 47 patients ( 87 % ) . 41 patients with neurtopenia were r and omized into two groups . The first group--22 patients who received granulocyte colony-stimulating factor ( G-CSF , or filgrastim ) 300 mcg s/c weekly for correction of neutropenia and the second group--19 patients treated either with Interferon dose reduction or temporarily inhibit of Interferon treatment . In all 22 patients of the first group neutropenia was normalized without reduction and /or inhibit of Pegylated interferon . Neupogen was well tolerated and in all 22 patients the improvement of quality of life ( QOL ) was observed . It was concluded that dose reduction or temporary inhibit of Pegylated Interferon in the second group negatively acts on antiviral treatment response in patients with HCV genotype 1 . In patients with PEG-IFN/RBV therapy Neupogen effectively manages neutropenia and gives opportunity to maintain interferon dose ( without reduction ) . Neupogen has the potential to improve adherence rates , which may in turn improve SVR Ischemic preconditioning ( IPC ) has the potential to decrease graft injury and morbidity after liver transplantation . We prospect ively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers r and omized 1:1 to st and ard ( STD ) recovery ( N = 28 ) or IPC ( N = 34 ) . Safety was assessed by measurement of heart rate , blood pressure , and visual inspection of abdominal organs during recovery , and efficacy by recipient aminotransferases ( aspartate aminotransferase [ AST ] and alanine aminotransferase [ ALT ] , both measured in U/L ) , total bilirubin , and international normalized ratio of prothrombin time ( INR ) after transplantation . IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion . Recipient median AST , median ALT , and mean INR , in STD vs. IPC were as follows : day 1 AST 696 vs. 841 U/L ; day 3 AST 183 vs. 183 U/L ; day 1 ALT 444 vs. 764 U/L ; day 3 ALT 421 vs. 463 U/L ; day 1 INR 1.7 + /- .4 vs. 2.0 + /- .8 ; and day 3 INR 1.3 + /- .2 vs. 1.4 + /- .3 ; all P > .05 . No instances of nonfunction occurred . The 6-month graft and patient survival STD vs. IPC were 82 vs. 91 % and median hospital stay was 10 vs. 8 days ; both P > .05 . In conclusion , deceased donor livers tolerated 5 minutes of hilar clamping well , but IPC did not decrease graft injury . Further trials with longer periods of preconditioning such as 10 minutes are needed BACKGROUND & AIMS Recurrence of hepatitis C virus ( HCV ) infection is a relevant problem of liver transplantation programs . We evaluated the effect of antiviral therapy on disease progression in 81 HCV-infected liver transplantation recipients . METHODS Patients with mild hepatitis C recurrence ( fibrosis stage F0 to F2 , n = 54 ) were r and omized to no treatment ( group A , n = 27 ) or peginterferon alfa-2b/ribavirin for 48 weeks ( group B , n = 27 ) . Patients with severe recurrence ( F3 to F4 , cholestatic hepatitis ) were treated ( group C , n = 27 ) . All patients ( n = 81 ) underwent a liver biopsy at baseline and after follow-up ; paired hepatic venous pressure gradient ( HVPG ) measurements were available in 51 patients . RESULTS Thirteen ( 48 % ) patients of group B and 5 ( 18.5 % ) of group C achieved sustained virological response . Liver fibrosis progressed > or = 1 stage in 40 ( 49 % ) of 81 patients : 19 ( 70 % ) of group A versus 7 ( 26 % ) of group B ( P = .001 ) and in 14 ( 54 % ) of group C. HVPG increased ( 6.5 to 13 mm Hg , P < .01 ) in patients in whom fibrosis worsened , whereas it decreased ( 5 to 3.5 mm Hg , P = .017 ) or remained unchanged in those with fibrosis improvement or stabilization , respectively . The only variable independently associated with fibrosis improvement/stabilization was treatment ( odds ratio [ OR ] = 3.7 , 95 % confidence interval [ CI ] 1.3 to 10 , P = .009 ) . Among treated patients , alanine aminotransferase ( ALT ) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization ( OR 5.3 , 95 % CI 1.5 to 18 , P < .01 ; OR 7.4 , 95 % CI 1.4 to 38 , P = .01 ; respectively ) . CONCLUSIONS Our data demonstrate that in liver transplantation recipients , antiviral therapy slows disease progression ( particularly in sustained virological responders ) , as shown by its effects on liver histology and on HVPG Allograft reinfection with hepatitis C virus ( HCV ) in transplant recipients occurs commonly and represents a major concern in the transplant setting . Suppression of viral replication in HCV transplant patients should prevent or delay progression to cirrhosis and graft failure . In this ongoing study , we present preliminary data from a prospect i ve trial of st and ard interferon ( IFN ) alpha-2b ( 2 million units daily ) for 3 months and subsequent peginterferon ( PEG IFN ) alpha-2b ( 1.5 microg/kg/week ) for 9 months . IFN therapy was combined with ribavirin ( 10 to 12 mg/kg ) . So far , HCV has become undetectable by qualitative PCR in 33 % of patients while 25 % had a reduction of HCV RNA to undetectable by the bDNA assay and 42 % had no virological response after 6 months of therapy . A biochemical response was detected in 42 % of patients . Improvement of inflammatory activity was observed in 42 % of patients after 6 months . In three patients anemia necessitated administration of erythropoietin and three patients received granulocyte-colony stimulating factor ( G-CSF ) due to leucopenia [ corrected ] In conclusion , we observed that daily IFN alpha-2b and subsequent PEG IFN alpha-2b therapy in combination with ribavirin provides biochemical and virological benefits in transplant recipients with established recurrent HCV infection BACKGROUND / AIMS HCV infection recurs almost in all HCV-positive patients receiving liver transplantation and carries a poor prognosis . Aim of this study was to analyze efficacy and effect on survival of antiviral therapy in this clinical setting . METHODS Pegylated-interferon alpha-2b and ribavirin were administered at a dose of 1 microg/kg of bwt weekly and 600 - 800 mg/day . Planned duration of treatment was 24 or 48 weeks according to HCV genotype . Patients who failed to respond at week 24 were considered as non-responders . RESULTS 61 patients were enrolled . According to intention-to-treat analysis , 44 ( 72 % ) patients were considered as treatment failure ( 31 non-responders , 4 relapsers , 9 dropout ) . Sustained virological response was achieved in 17 cases ( 28 % ) . Genotype 2 , higher doses of antivirals and absence of histological cirrhosis were predictors of sustained virological response . In the follow up , patients with sustained virological response had a significantly lower mortality compared to patients with treatment failure ( chi2=6.9 ; P<0.01 ) . CONCLUSIONS Response rate to antiviral therapy in HCV reinfection after liver transplantation is higher if a full dose of antiviral drugs is administered and if treatment starts before histological cirrhosis has developed . Sustained virological response improves patient survival The effect of ischemic preconditioning ( IPC ) in orthotopic liver transplantation ( OLT ) has not yet been clarified . We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors r and omly assigned to receive ( IPC+ group , n = 23 ) or not ( IPC- group , n = 24 ) IPC ( 10-min ischemia + 15-min reperfusion ) . In 10 cases in the IPC+ group and in 12 in the IPC- group , the expression of inducible nitric oxide synthase ( iNOS ) , neutrophil infiltration , and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies . Median aspartate aminotransferase ( AST ) levels were lower in the IPC+ group vs. the IPC- group on postoperative days 1 and 2 ( 398 vs. 1,234 U/L , P = 0.002 ; and 283 vs. 685 U/L , P = 0.009 ) . Alanine aminotransferases were lower in the IPC+ vs. the IPC- group on postoperative days 1 , 2 , and 3 ( 333 vs. 934 U/L , P = 0.016 ; 492 vs. 1,040 U/L , P = 0.008 ; and 386 vs. 735 U/L , P = 0.022 ) . Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks , incidence of graft nonfunction and graft and patient survival rates were similar between groups . Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups . iNOS was higher postreperfusion vs. prereperfusion in the IPC- group ( P = 0.008 ) . Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups ( IPC+ , P = 0.007 ; IPC- , P = 0.003 ) . Prereperfusion and postreperfusion apoptosis was minimal in both groups . In conclusion , IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis , but it showed no clinical benefits BACKGROUND AND AIMS Hepatitis C virus ( HCV ) reinfection after liver transplantation is frequent and leads to chronic hepatitis and cirrhosis . The use of antiviral therapy in this situation remains controversial . This study aim ed to assess the safety and efficacy of interferon alfa-2b plus ribavirin for recurrent hepatitis C following liver transplantation . METHODS Transplant recipients with recurrent chronic hepatitis C were r and omized to receive either no treatment or therapy with interferon alfa-2b ( 3 MU 3 times a week ) plus 1000 - 1200 mg/day ribavirin for 1 year . Patients were followed up for 6 months after the end of treatment . The primary end point was loss of HCV RNA 6 months after the end of treatment . RESULTS Fifty-two patients were r and omized ( treatment , 28 ; placebo , 24 ) . Sixteen patients were withdrawn from the study ; 12 ( 43 % ) were from the treated group ( mainly for anemia [ 7 patients ] ) and 4 ( 17 % ) from the control group . In the treated group , serum HCV RNA was undetectable in 9 patients ( 32 % ) at the end of treatment and 6 ( 21.4 % ) at the end of the follow-up period , whereas no patient in the control group lost HCV RNA at any point ( P = 0.036 at the end of follow-up ) . However , there was no significant histologic improvement . CONCLUSIONS The combination of interferon alfa-2b plus ribavirin induced a sustained virologic response in 21 % of transplant recipients with recurrent hepatitis C. However , 43 % discontinued therapy due to adverse events ( primarily severe anemia ) . Strategies to enable treatment with lower doses of ribavirin need to be explored Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . The aim of the 18 months follow up study was to assess the frequency of anemia during IFN/RBV therapy in patients with chronic hepatitis C ; to manage anemia either with recombinant human erythropoietin (rHuEPO)--epoetin alpha or with RBV dose reduction and to compare the rate of SVR in patients with RBV dose reduction and with administration of epoetin alpha . Study enrolled 61 patients with chronic active hepatitis C aged 33 - 61 years . All patients had HCV genotype 1b . Out of them 41 were male and 20 female . Anemia ( Hb < 10 or > 2 g/dL Hgb drop from baseline ) developed in 41 patients out of 61 ( 67,21 % ) during the therapy . These 41 patients were r and omized into two groups : 21 patients who received 40 000 IU epoetin alpha weekly ( I group ) and 20 patients in whom for managing anemia we used st and ard of care ( SOC ) or RBV dose reductions from 1000/1200 to 800/600 mg ( II group ) . In all 21 patients of the I group the Hb level normalized without reduction of RBV dose . In this group of patients SVR at 6 months after completion of full course of treatment was achieved in 17 ( 66 % ) patients . Improvement of quality of life ( QOL ) was observed in all 21 patients . Out of 20 patients of II group with st and ard of care ( SOC ) 5 patients developed symptomatic anemia with fatigue and dyspnoea ; RBV was stopped temporarily . In 15 patients RBV dose was reduced from 1200 mg to 600 mg for correction of anemia . In this group of patients SVR at 6 months after treatment completion was achieved in 7 ( 25 % ) patients . Lower RBV doses yield a lower treatment response in patients with HCV genotype 1 . In anemic HCV-infected patients on RBV/PEG-IFN therapy , EPO maintains RBV dose and significantly improves anemia and QOL . EPO has the potential to improve adherence rate , which may in turn improve SVR Decompensated liver disease associated with chronic hepatitis C virus ( HCV ) infection is the most common indication for liver transplantation . It was shown previously that greater pretransplantation HCV titers are associated with relatively poor patient and graft survival . The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known . We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa-2b , with or without ribavirin . HCV RNA-positive patients at or near the top of their respective waiting lists were r and omly assigned to one of three treatment regimens until the time of liver transplantation : ( 1 ) group A , interferon alfa-2b , 1 x 10(6 ) U/d ; ( 2 ) group B , interferon alfa-2b , 3 x 10(6 ) U three times weekly ; or ( 3 ) group C , interferon alfa-2b , 1 x 10(6 ) U/d , plus ribavirin , 400 mg twice daily . Less than half the patients screened met entry criteria , with thrombocytopenia and leukopenia the most common reasons for exclusion . Fifteen patients were administered antiviral therapy ; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33 % of patients , whereas 55 % had a decrease in viral titers on therapy . Twenty-three adverse events occurred , including 20 serious adverse events . Thrombocytopenia was the most common adverse event . Two infectious complications occurred ; one of these had a fatal outcome . We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria , adverse events associated with therapy are frequent and often severe in patients with Child 's class B and C cirrhosis Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection . Steroids also have been held responsible for increased infections , posttransplantation diabetes , and recurrent hepatitis after orthotopic liver transplantation ( OLT ) . The purpose of this ongoing prospect i ve r and omized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin ( RATG ) . This is the first report of a prospect i ve r and omized trial in OLT achieving complete absence of steroids . Seventy-one adult patients were prospect ively r and omized to administration of RATG or steroids . Thirty-six patients were r and omized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously ( IV ) beginning during the anhepatic phase . No steroids were administered . Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1 . Thirty-five patients were r and omized to the administration of methylprednisolone , which had been our st and ard immunosuppressive protocol . These patients were administered methylprednisolone , 1,000 mg IV , initiated during the anhepatic phase and followed by steroid taper . Maintenance immunosuppression consisted of tacrolimus and mycophenolate , with or without prednisone . Three patients died in each group , for an overall survival rate of 91 % in each group . One patient in each group required re-OLT , for a graft survival rate of 89 % in each group . Seven patients administered RATG had biopsy-proven rejection ( 20.5 % ) , all of whom were successfully treated by increasing tacrolimus doses . Eleven patients administered steroid had biopsy-proven rejection ( 32 % ) , 7 ( 64 % ) of whom required additional steroids for treatment , whereas 4 patients ( 36 % ) were successfully treated by increasing tacrolimus doses . The incidence of rejection was not statistically significant ; however , there was a significant difference in the incidence of steroid-requiring rejection ( P = .01 ) . The incidence of recurrent hepatitis C was 50 % in RATG patients and 71 % in steroid patients ( P = not significant ) . The incidence and severity of infectious complications were slightly lower in RATG patients , accounted for by a greater incidence of cytomegalovirus ( CMV ) infection in the steroid patients . RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate , decreased incidence of post-OLT diabetes and recurrent hepatitis C , and decreased CMV infection . This prospect i ve r and omized trial gives encouraging support that steroids can be safely eliminated in OLT There is currently no effective treatment for recurrent hepatitis C after orthotopic liver transplantation ( OLT ) . We therefore performed two r and omized , controlled trials -- a prophylaxis trial and a treatment trial -- to evaluate the safety and efficacy of peginterferon alfa-2a in patients who had undergone OLT . The prophylaxis trial enrolled 54 patients within 3 weeks after OLT , and the treatment trial enrolled 67 patients 6 to 60 months after OLT . In each trial , patients were r and omized to treatment with once weekly injections of 180 microg peginterferon alfa-2a or no antiviral treatment for 48 weeks and were followed up for 24 weeks thereafter . Peginterferon alfa-2a treated patients had significantly lower hepatitis C virus RNA levels and more favorable changes in hepatic histological features compared with untreated controls . However , only 2 treated patients in the prophylaxis trial ( 8 % ) and 3 in the treatment trial ( 12 % ) achieved a sustained virological response . In the prophylaxis trial , 8 patients ( 31 % ) in the peginterferon alfa-2a group and 9 ( 32 % ) in the untreated group were withdrawn prematurely ; whereas in the treatment trial , 10 patients ( 30 % ) in the peginterferon alfa-2a group and 6 ( 19 % ) in the untreated group were withdrawn prematurely . The incidence of acute rejection was similar in the treated and untreated groups in both the prophylaxis ( 12 % vs. 21 % ; P = .5 ) and treatment ( 12 % vs. 0 % ; P = .1 ) trials . In conclusion , peginterferon alfa-2a treatment for 48 weeks is safe and tolerable and offers some efficacy in the post-OLT setting . R and omized controlled studies are needed to establish the efficacy of pegylated interferon and ribavirin in patients who have undergone OLT Hepatitis C virus ( HCV ) infection usually recurs after orthotopic liver transplantation ( OLT ) , and most patients develop graft damage . This study compared the efficacy of interferon alfa ( IFN-alpha ) and ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft . Thirty OLT recipients with chronic hepatitis C were r and omized to receive either IFN-alpha ( 3 MU three times a week ) or ribavirin ( up to 1.2 g daily ) for 24 weeks . Virological , biochemical , and histological responses to treatment were assessed . Twenty-eight patients completed the treatment regimen , two ribavirin-treated patients being withdrawn because of severe hemolysis . Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin ( 93 % ) and 6 of 14 patients receiving IFN-alpha ( 43 % ; P=.01 ) . Lobular inflammation was reduced in 9/14 ribavirin-treated ( 64 % ) and 3 of 14 IFN-alpha-treated patients ( 21 % ; P=.05 ) , each of whom had a biochemical response . However , the total histological activity index did not improve in either the interferon ( P=.43 ) or the ribavirin ( P=.96 ) group . Posttreatment viremia levels were significantly reduced in IFN-alpha-treated ( P=.05 ) but not in ribavirin-treated ( P=.88 ) patients . Hemolysis occurred in all ribavirin-treated patients , with serum hemoglobin decreasing to < 10 g/dL in 50 % . Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment ( P=.02 and P=.004 , respectively ) . We concluded that in patients with chronic hepatitis C after OLT , IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation , but not the total histological activity index . These findings provide a rationale for combination therapy in the post-OLT setting , although patients must be carefully monitored for hemolysis Background . Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of patients . St and ard dose interferon therapy has been largely unsuccessful for hepatitis C in transplant recipients . Methods . Twelve patients , at least 7 months posttransplant , with detectable hepatitis C virus RNA in serum and features of hepatitis C on liver biopsy were r and omized to interferon-&agr;2a , 3 mU daily for 12 months ( n=8 ) or no treatment ( n=4 ) . The tolerability of daily interferon dosing in liver transplant recipients was evaluated and effects on hepatitis C virus RNA level , quasispecies evolution , and liver histology were studied . Results . Treated patients had an improvement in histological activity index at the end of therapy relative to controls ( median reduction of 2 versus median increase of 1.5 ) ( P = 0.04 ) . Four treated patients had a virological response ( all bDNA negative , one qualitative polymerase chain reaction negative ) compared with none of the untreated patients . Only two of six treated patients tested had evidence of quasispecies diversification on therapy . Seven of eight patients in the treatment group required dose reduction for fatigue and /or depression . They tolerated 1.5 mU of interferon-&agr;2a daily . Two treated patients developed graft dysfunction , one of who had histological evidence of rejection and subsequent graft loss . Conclusions . Low daily doses of interferon were tolerated by liver transplant recipients and provided histological benefit without associated quasispecies diversification in most cases . These findings provide a rationale to study low dose daily or pegylated interferon maintenance therapy for the management of hepatitis C posttransplant BACKGROUND & AIMS We aim ed at determining the effect of maintenance therapy with ribavirin alone , after a year of combined peginterferon-alfa 2a ( PegIFNα-2a ) and ribavirin therapy , on viral response and liver histology after liver transplantation ( LT ) . METHODS Hundred and one patients with recurrent HCV and a minimum of stage 1 fibrosis ( METAVIR scoring ) , 1 - 5years after LT , were enrolled . PegIFNα-2a and ribavirin were initiated at 90 μg/wk and 600 mg/d , respectively , then increased or adjusted as a function of tolerance . At 12 months , combination therapy was discontinued and patients were r and omized to ribavirin or placebo for a further 12 months . Growth factor use was permitted . RESULTS At 18 months , a sustained virological response ( SVR ) was obtained in 47.9 % of patients in Per Protocol ( PP ) analysis , and was higher in patients with genotype 2 or 3 than in patients with genotype 1 or 4 , in patients with genotypes 1 + 4 receiving ciclosporine than in those receiving tacrolimus , in patients with worse renal function , in those having received EPO , in patients with lower weight , and in those with lower viral load at 3 months . Using logistic regression , only the early viral response , recipient weight and renal function were independently associated with better SVR . SVR , viral load , activity , and fibrosis scores were similar , at M18 and M30 , in patients r and omized to ribavirin , or to placebo . CONCLUSIONS A PP SVR was achieved in 47.9 % of patients with established recurrent hepatitis C after LT . Maintenance therapy with ribavirin alone does not improve the virological response or the histological parameters BACKGROUND / AIMS We performed a r and omized trial on pegylated interferon alfa-2a ( Peg-IFNalpha ) monotherapy vs Peg-IFNalpha and ribavirin in non-cirrhotic liver transplant recipients with recurrent hepatitis C. METHODS Forty-two patients transplanted for HCV-related cirrhosis 12 - 96 months earlier were r and omized to Peg-IFNalpha monotherapy ( 180 microg weekly ) or Peg-IFNalpha and ribavirin , up to the maximum tolerated dose , for 48 weeks . RESULTS Early virological response ( EVR , i.e. , HCV-RNA2 log drop at week 12 ) occurred in 76 % of the monotherapy and 71 % of the combination groups , respectively ( intention-to treat ) . Sustained virological response ( SVR ) occurred in 8 ( 38 % ) and 7 ( 33 % ) patients , respectively . EVR had a positive predictive value for SVR of 50 % and 47 % , respectively , and a 100 % negative predictive value in both groups . Six drop-outs occurred in the monotherapy ( including 3 rejections ) and 7 in the combination groups ( including one rejection ) . Peg-INFalpha dose was reduced in 7 and 8 patients , respectively . The average daily dose of ribavirin was 435 mg/day . CONCLUSIONS Peg-IFNalpha-2a , with or without ribavirin , induces SVR in one-third of transplant recipients with recurrent hepatitis C. Treatment cessation is indicated in patients without EVR . The low SVR rate is mainly due to inability to sustain full doses of antivirals and lack of the booster effect of ribavirin BACKGROUND & AIMS Combination therapy with interferon alpha ( IFN-alpha ) and ribavirin ( RBV ) or pegylated IFN-alpha (PEG-IFN-alpha)/RBV for chronic hepatitis C virus ( HCV ) infection often causes anemia , prompting RBV dose reduction/discontinuation . This study assessed whether epoetin alfa could maintain RBV dose , improve quality of life ( QOL ) , and increase hemoglobin ( Hb ) in anemic HCV-infected patients . METHODS HCV-infected patients ( n = 185 ) on combination therapy who developed anemia ( Hb < or = 12 g/dL ) were r and omized into a U. S. multicenter , placebo-controlled , clinical trial of epoetin alfa , 40,000 U subcutaneously , once weekly vs. matching placebo . The study design used an 8-week , double-blind phase ( DBP ) followed by an 8-week , open-label phase ( OLP ) , in which placebo patients were crossed over to epoetin alfa . RESULTS At the end of the DBP , RBV doses were maintained in 88 % of patients receiving epoetin alfa vs. 60 % of patients receiving placebo ( P < 0.001 ) . Mean QOL scores at the end of the DBP improved significantly on all domains of the Linear Analog Scale Assessment ( LASA ) and on 7 of the 8 domains of the Short Form-36 , version 2 ( SF-36v2 ) . Mean Hb increased by 2.2 + /- 1.3 g/dL ( epoetin alfa ) and by 0.1 + /- 1.0 g/dL ( placebo ) in the DBP ( P < 0.001 ) . Similar results were demonstrated in patients who switched from placebo to epoetin alfa in the OLP . Epoetin alfa was well tolerated ; the most common adverse effects were headache and nausea . CONCLUSIONS Epoetin alfa maintained RBV dose and improved QOL and Hb in anemic HCV-infected patients receiving combination therapy Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
12,430 | 31,848,862 | Twenty-nine studies of interventions aim ed at improving clinician-patient communication in clinical setting s. We identified acceptability , adoption , appropriateness , feasibility , fidelity , implementation cost , intervention complexity , penetration , reach , and sustainability as factors that are feasible and appropriate to extract during an evidence synthesis project .
Abstract ing information about these factors may enhance the value of systematic review s and other evidence synthesis efforts , improving the dissemination and adoption of interventions that are effective , feasible , and sustainable across different context | In order to close the gap between discoveries that could improve health , and widespread impact on routine health care practice , there is a need for greater attention to the factors that influence dissemination and implementation of evidence -based practice s. Evidence synthesis projects ( e.g. , systematic review s ) could contribute to this effort by collecting and synthesizing data relevant to dissemination and implementation .
Such an advance would facilitate the spread of high-value , effective , and sustainable interventions .
The objective of this paper is to evaluate the feasibility of extracting factors related to implementation during evidence synthesis in order to enhance the replicability of successes of studies of interventions in health care setting s. Drawing on the implementation science literature , we suggest 10 established implementation measures that should be considered when conducting evidence synthesis projects .
We describe opportunities to assess these constructs in current literature and illustrate these methods through an example of a systematic review . | Background It is increasingly acknowledged that ‘ acceptability ’ should be considered when design ing , evaluating and implementing healthcare interventions . However , the published literature offers little guidance on how to define or assess acceptability . The purpose of this study was to develop a multi-construct theoretical framework of acceptability of healthcare interventions that can be applied to assess prospect i ve ( i.e. anticipated ) and retrospective ( i.e. experienced ) acceptability from the perspective of intervention delivers and recipients . Methods Two methods were used to select the component constructs of acceptability . 1 ) An overview of review s was conducted to identify systematic review s that cl aim to define , theorise or measure acceptability of healthcare interventions . 2 ) Principles of inductive and deductive reasoning were applied to theorise the concept of acceptability and develop a theoretical framework . Steps included ( 1 ) defining acceptability ; ( 2 ) describing its properties and scope and ( 3 ) identifying component constructs and empirical indicators . Results From the 43 review s included in the overview , none explicitly theorised or defined acceptability . Measures used to assess acceptability focused on behaviour ( e.g. dropout rates ) ( 23 review s ) , affect ( i.e. feelings ) ( 5 review s ) , cognition ( i.e. perceptions ) ( 7 review s ) or a combination of these ( 8 review s).From the methods described above we propose a definition : Acceptability is a multi-faceted construct that reflects the extent to which people delivering or receiving a healthcare intervention consider it to be appropriate , based on anticipated or experienced cognitive and emotional responses to the intervention . The theoretical framework of acceptability ( TFA ) consists of seven component constructs : affective attitude , burden , perceived effectiveness , ethicality , intervention coherence , opportunity costs , and self-efficacy . Conclusion Despite frequent cl aims that healthcare interventions have assessed acceptability , it is evident that acceptability research could be more robust . The proposed definition of acceptability and the TFA can inform assessment tools and evaluations of the acceptability of new or existing interventions OBJECTIVE This study examines hospital motivations to acquire new medical technology , an issue of considerable policy relevance : in this case , whether , when , and why hospitals acquire a new capital-intensive medical technology , magnetic resonance imaging equipment ( MRI ) . STUDY DESIGN We review three common explanations for medical technology adoption : profit maximization , technological preeminence , and clinical excellence , and incorporate them into a composite model , controlling for regulatory differences , market structures , and organizational characteristics . All four models are then tested using Cox regressions . DATA SOURCES The study is based on an initial sample of 637 hospitals in the continental United States that owned or leased an MRI unit as of 31 December 1988 , plus nonadopters . Due to missing data the final sample consisted of 507 hospitals . The data , drawn from two telephone surveys , are supplemented by the AHA Survey , census data , and industry and academic sources . PRINCIPAL FINDING Statistically , the three individual models account for roughly comparable amounts of variance in past adoption behavior . On the basis of explanatory power and parsimony , however , the technology model is " best . " Although the composite model is statistically better than any of the individual models , it does not add much more explanatory power adjusting for the number of variables added . CONCLUSIONS The composite model identified the importance a hospital attached to being a technological leader , its clinical requirements , and the change in revenues it associated with the adoption of MRI as the major determinants of adoption behavior . We conclude that a hospital 's adoption behavior is strongly linked to its strategic orientation Incomplete and inadequate reporting is an avoidable waste that reduces the usefulness of research . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement is an evidence -based reporting guideline that aims to improve research transparency and reduce waste . In 2008 , the CONSORT Group developed an extension to the original statement that addressed method ological issues specific to trials of nonpharmacologic treatments ( NPTs ) , such as surgery , rehabilitation , or psychotherapy . This article describes an up date of that extension and presents an extension for reporting abstract s of NPT trials . To develop these material s , the authors review ed pertinent literature published up to July 2016 ; surveyed authors of NPT trials ; and conducted a consensus meeting with editors , trialists , and method ologists . Changes to the CONSORT Statement extension for NPT trials include wording modifications to improve readers ' underst and ing and the addition of 3 new items . These items address whether and how adherence of participants to interventions is assessed or enhanced , description of attempts to limit bias if blinding is not possible , and specification of the delay between r and omization and initiation of the intervention . The CONSORT extension for abstract s of NPT trials includes 2 new items that were not specified in the original CONSORT Statement for abstract s. The first addresses reporting of eligibility criteria for centers where the intervention is performed and for care providers . The second addresses reporting of important changes to the intervention versus what was planned . Both the up date d CONSORT extension for NPT trials and the CONSORT extension for NPT trial abstract s should help authors , editors , and peer review ers improve the transparency of NPT trial reports |
12,431 | 22,030,332 | Despite study diversity and limitations , evidence suggests that treatment supporters , directly observed therapy , mobile-phone text messages , diary cards , and food rations can effectively increase adherence in sub-Saharan Africa . | The success of potent antiretroviral treatment for HIV infection is primarily determined by adherence .
We systematic ally review the evidence of effectiveness of interventions to increase adherence to antiretroviral treatment in sub-Saharan Africa . | Background Human re source limitations are a challenge to the delivery of antiretroviral therapy ( ART ) in low-re source setting s. We conducted a cluster r and omized trial to assess the effect of community-based peer health workers ( PHW ) on AIDS care of adults in Rakai , Ug and a. Methodology /Principal Findings 15 AIDS clinics were r and omized 2∶1 to receive the PHW intervention ( n = 10 ) or control ( n = 5 ) . PHW tasks included clinic and home-based provision of counseling , clinical , adherence to ART , and social support . Primary outcomes were adherence and cumulative risk of virologic failure ( > 400 copies/mL ) . Secondary outcomes were virologic failure at each 24 week time point up to 192 weeks of ART . Analysis was by intention to treat . From May 2006 to July 2008 , 1336 patients were followed . 444 ( 33 % ) of these patients were already on ART at the start of the study . No significant differences were found in lack of adherence ( < 95 % pill count adherence risk ratio [ RR ] 0.55 , 95 % confidence interval [ CI ] 0.23–1.35 ; < 100 % adherence RR 1.10 , 95 % CI 0.94–1.30 ) , cumulative risk of virologic failure ( RR 0.81 , 95 % CI 0.61–1.08 ) or in shorter-term virologic outcomes ( 24 week virologic failure RR 0.93 , 95 % CI 0.65–1.32 ; 48 week , RR 0.83 , 95 % CI 0.47–1.48 ; 72 week , RR 0.81 , 95 % CI 0.44–1.49 ) . However , virologic failure rates ≥96 weeks into ART were significantly decreased in the intervention arm compared to the control arm ( 96 week failure RR 0.50 , 95 % CI 0.31–0.81 ; 120 week , RR 0.59 , 95 % CI 0.22–1.60 ; 144 week , RR 0.39 , 95 % CI 0.16–0.95 ; 168 week , RR 0.30 , 95 % CI 0.097–0.92 ; 192 week , RR 0.067 , 95 % CI 0.0065–0.71 ) . Conclusions / Significance A PHW intervention was associated with decreased virologic failure rates occurring 96 weeks and longer into ART , but did not affect cumulative risk of virologic failure , adherence measures , or shorter-term virologic outcomes . PHWs may be an effective intervention to sustain long-term ART in low-re source setting s. Trial Registration Clinical Trials.gov Background : We prospect ively studied the impact of an adherence counselor on the outcome of patients failing antiretroviral therapy because of nonadherence . Methods : Forty-six patients , identified as chronically nonadherent were enrolled . Individual attention was provided using the information , motivation and behavioral methodology . HIV RNA ( viral load , in copies/mL ) , CD4 count ( in cells/mm 3 ) , and body weight before and after the adherence counselor were measured . Qualitative outcome and patient satisfaction were assessed by deidentified third-party interviews . Results : Over half completed at least 1 year ; only 8 patients were lost to follow-up . Mean CD4 counts increased significantly ( P < .05 ) for completers at 6 and 12 months . Viral loads decreased between baseline and 6 months . Most clients reported subjective benefit from working with the adherence counselor . Conclusion : Although few clients showed complete virologic suppression , the value of an adherence counselor was vali date d. Longer term adherence programs should be evaluated Objective : To determine the efficacy of patient-selected treatment partners on virologic and adherence outcomes during first-line antiretroviral therapy . Design : R and omized controlled trial . Setting and Analytical Approach : Between June 2006 and December 2007 , 499 HIV-infected adults in Jos , Nigeria , were r and omized to st and ard of care ( SOC ) or patient-selected treatment partner-assisted therapy ( TPA ) . Each patient was followed for 48 weeks . Virologic outcomes , adherence to drug pick-up , CD4 cell counts , and mortality are reported . Results : At week 24 , undetectable viral load was achieved by 61.7 % of patients in the TPA arm versus 50.2 % of those receiving SOC [ odds ratio ( OR ) = 1.58 , 95 % CI : 1.11 to 2.26 , P < 0.05 ] . There was no significant difference at week 48 : 65.3 % versus 59.4 % for TPA and SOC , respectively ( OR = 1.28 , 95 % CI : 0.89 to 1.84 , P > 0.05 ) . The TPA group had more than 3 times the odds of at least 95 % drug pickup adherence through week 24 ( OR = 3.06 , 95 % CI : 1.89 to 4.94 , P < 0.01 ) and almost twice the odds through week 48 ( OR = 1.95 , 95 % CI : 1.29 to 2.93 , P < 0.01 ) . At week 48 , there were no significant differences in CD4 cell count increases ( t = −0.09 , df = 404 , P > 0.05 ) or mortality ( 10.6 % vs. 6.1 % ) between TPA vs. SOC , respectively . Residence-to-clinic distance was significantly associated with virologic and adherence outcomes . Conclusions : Use of patient-selected treatment partners was associated with improved drug pickup adherence and initial virologic success but had no durable effect on attaining undetectable viral load A r and omized 2-group medication adherence intervention is evaluated with HIV-infected adults ( N = 141 ) assessed at baseline , 3- , and 9-month follow-ups . Cognitive ( self-efficacy , behavioral intent ) , mental health ( depression , well-being ) , and substance use indicators were the outcome measures . In addition , a posttest-only analysis from 3 to 9 months evaluates intervention impact on antiretroviral adherence , measured through Medication Event Monitoring System and pill counts . Compared to the st and ard care group , the intervention group showed significant increases in adherence self-efficacy and behavioral intent at 3 and 9 months and marginal improvements in mental health . Although the st and ard care group had higher adherence at 3 months ( no baseline data were available prior to intervention ) , intervention group patients showed significant increases in adherence from 3 to 9 months . Although adherence levels achieved by intervention patients may not be sufficient for virological control , this is one of the first studies to provide promising results of longer term effectiveness of a behavioral adherence intervention Context Highly active antiretroviral therapy ( HAART ) improves outcomes in HIV-infected patients . When is the best time to start this therapy ? Contribution 1422 HIV-infected adults were followed for 2 to 6 years after starting HAART . Adherent patients who started treatment with lower ( 0.200 to 0.349 109 cells/L ) and higher ( 0.350 109 cells/L ) CD4 + cell counts had statistically similar mortality rates . Nonadherent patients had higher mortality rates than adherent patients , regardless of baseline CD4 + cell count of 0.200 to 0.349 109 cells/L or 0.350 109 cells/L or greater . Implication s In HIV-infected patients , adherence , rather than when therapy is initiated before a CD4 + cell count of 0.200 109 cells/L , may be the most important determinant of survival . The Editors The benefits of highly active antiretroviral therapy ( HAART ) in the management of HIV disease are well established . By suppressing plasma HIV-1 RNA , HAART decreases morbidity and mortality in HIV-infected patients ( 1 , 2 ) . However , the optimal time to initiate HAART is uncertain . As a result , expert recommendations on the optimal time to initiate antiretroviral therapy widely differ ( 3 - 6 ) . Several studies have suggested that only patients who initiated therapy when the CD4 + cell count had declined below 0.200 109 cells/L were at increased risk for disease progression , regardless of the baseline HIV RNA level ( 7 - 9 ) . In 1 of these studies , further examination with additional duration of follow-up suggested that mortality may be elevated in patients who initiated therapy after the CD4 + cell count declined below 0.350 109 cells/L ( 10 ) . In fact , a growing number of studies have suggested that delaying HAART after the CD4 + cell count declines below 0.350 109 cells/L may be unsafe ( 11 - 14 ) . However , previous studies ( 7 , 9 , 11 - 14 ) did not adjust for patient adherence . This limitation is critically important because incomplete adherence is associated with increased mortality ( 15 - 17 ) . Therefore , we sought to evaluate the effect of baseline CD4 + cell count and adherence on survival rates after the initiation of HAART . Methods The HAART Observational Medical Evaluation and Research ( HOMER ) study , conducted through the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program , has been described in detail elsewhere ( 7 , 17 ) . Briefly , the Centre is the only free source of antiretroviral medications in British Columbia , Canada ; pharmaceutical sales suggest that less than 1 % of HIV-infected patients in this province obtain antiretroviral agents outside the program ( 18 ) . For all participants , the program maintains a complete prospect i ve profile of antiretroviral therapy . In the present study , we restricted analyses to HIV-infected men and women who had been antiretroviral naive until triple-drug antiretroviral therapy was prescribed between 1 August 1996 and 31 July 2000 and were followed through 31 March 2002 . Study participants were initially prescribed HAART regimens that included 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor ( the enrolling physician , in consultation with the patient , chose the regimen ) . End Points The primary end point in this analysis was time to death . Deaths occurring during the follow-up period were continuously identified from physician reports and through record linkages with the British Columbia Division of Vital Statistics . In the primary analysis , we evaluated all-cause mortality ; in subanalyses , we censored deaths from accidental causes at the time of death and classified them as nonevents ( 7 ) . Statistical Analysis KaplanMeier Analyses For the KaplanMeier analyses , we stratified patients into 5 baseline CD4 + cell count strata on the basis of previous studies and the recommendations of therapeutic guidelines : less than 0.200 , 0.200 to 0.249 , 0.250 to 0.299 , 0.300 to 0.349 , and greater than or equal to 0.350 109 cells/L ( 3 - 5 , 7 - 9 ) . We further stratified patients into adherent and nonadherent categories according to adherence to prescription refills ( 19 ) . The definition of adherence was based on the ratio of time that medication dispensed would last as a proportion of follow-up time . This calculation was restricted to each patient 's first year of therapy in order to limit the potential for reverse causation in patients who ceased antiretroviral therapy after they became too sick to take medication ( 15 , 20 ) . We have previously demonstrated that adherence defined in this way strongly predicts virologic response and mortality and that it can be used to adjust for the potentially confounding effect of treatment interruption ( 15 , 17 , 21 , 22 ) . In the primary analysis , we wanted to evaluate how moderate adherence to HAART affected survival . Therefore , to estimate the effect of moderate adherence , a priori we categorized patients as nonadherent only if they received antiretroviral medications less than 75 % of the time during the first year of therapy ( 15 , 17 ) . In a sub analysis , we estimated the risk for death from HIV disease among patients who were highly adherent to HAART . We defined adherence more rigorously for this analysis ; patients were considered nonadherent only if they received antiretroviral medications less than 95 % of the time during the first year of therapy ( 21 , 23 ) . We also censored deaths from accidental causes at the time of death and classified them as nonevents ( 7 ) . For both analyses , we evaluated the cumulative mortality rates among the predefined baseline CD4 + cell count strata using KaplanMeier methods . Survival curves were compared by using the log-rank test . Cox Regression Analyses We were aware that additional confounding may persist if the distribution of baseline AIDS diagnoses or baseline HIV RNA levels differed between patients with various baseline CD4 + cell counts ( 9 ) . Therefore , we performed Cox proportional-hazards regression analyses to calculate the adjusted relative hazards of mortality ( 24 ) . In these analyses , we stratified patients into combined low ( < 0.200 109 cells/L ) , medium ( 0.200 to 0.349 109 cells/L ) , and high ( 0.350 109 cells/L ) CD4 + cell count strata ( 3 - 5 , 7 - 9 ) . To derive adjusted relative hazards of mortality among adherent and nonadherent patients in the various CD4 + cell count strata , we built fixed models with indicator variables for each adherence and CD4 + cell count strata while adjusting for baseline HIV RNA level and other relevant covariates . Variables examined in these analyses included protease inhibitor use in the initial regimen ( yes or no ) , a previous clinical diagnosis of AIDS ( yes or no ) , age , sex , physician experience ( 6 patients previously enrolled in the program ) ( 17 ) , date of therapy initiation ( before or after July 1997 ) ( 25 ) , and baseline HIV RNA levels ( log10-transformed ) . The assumption of proportional hazards was vali date d by inspection of log ( log [ survival function ] ) estimates against log time plots . We fit all multivariate models by adjusting for all variables that were statistically significant ( P < 0.05 ) in univariate analyses . Role of the Funding Sources The funding sources had no role in the design , conduct , or reporting of the study or the decision to su bmi t the manuscript for publication . Results Between 1 August 1996 and 31 July 2000 , 1583 antiretroviral-naive participants 18 years of age and older began triple-drug therapy . Of these , 161 ( 10 % ) were excluded from this analysis because baseline CD4 + cell count and plasma HIV-1 RNA levels were not available within 6 months before the start of antiretroviral therapy . Therefore , the study sample was based on 1422 ( 90 % ) participants ( 1198 men [ 84 % ] and 224 women [ 15 % ] ) . Sex , presence of AIDS at baseline , and subsequent mortality did not differ between the study sample and the persons excluded . However , excluded persons were more likely to be younger ( P = 0.04 ) and to be taking protease inhibitors ( P = 0.02 ) . The overall median follow-up time was 40.1 months ( interquartile range , 27.7 to 52.9 months ) . At baseline , the median patient age was 37 years ( interquartile range , 32 to 44 years ) , the median CD4 + cell count was 0.270 109 cells/L ( interquartile range , 0.130 to 0.420 109 cells/L ) , and the median plasma HIV RNA level was 120 000 copies/mL ( interquartile range , 38 000 to 300 000 copies/mL ) . Initial therapy was a protease inhibitor in 983 ( 69.1 % ) patients and a nonnucleoside reverse transcriptase inhibitor in 439 ( 31 % ) patients . During the study period , 193 patients died : 25 ( 13 % ) as a result of an accident or suicide and 14 ( 7 % ) as a result of an illicit drug overdose . Compared with patients who were less than 75 % adherent , patients who were at least 75 % adherent were more likely to be male ( 78.0 % vs. 59.4 % ) and older ( 37.9 years vs. 35.4 years ) and were less likely to have a history of injection drug use ( 78.3 % vs. 65.5 % ) ( P < 0.05 for all comparisons ) . In the primary analysis that considered all-cause mortality and 75 % adherence , 45 of the 632 patients with at least 75 % adherence who initiated HAART before the CD4 + cell count reached 0.200 109 cells/L had died by 31 March 2002 ; the crude mortality rate was 7.1 % ( Figure 1 , left ) . Conversely , among the 264 patients who started HAART when the CD4 + cell count was 0.200 109 cells/L or greater and who were less than 75 % adherent , 40 had died ( crude mortality rate , 15.2 % ) ( Figure 1 , right ) . The absolute difference in crude mortality between adherent and nonadherent patients with a baseline CD4 + cell count of 0.200 109 cells/L or greater was 8.1 percentage points ( Table 1 ) . In KaplanMeier analyses , when patients were considered according to the CD4 + cell count strata ( < 0.200 , 0.200 to 0.249 , 0.250 to 0.299 , 0.300 to 0.349 , and 0.350 109 cells/L ) , starting HAART at a CD4 + count of 0.200 109 cells/L or greater had no survival benefit in the 632 patients who were at least 75 % adherent ( Figure 1 , left ) . Table 2 shows the log-rank P values and estimated CIs comparing patients Objective To investigate the effect of two different food supplements on body mass index ( BMI ) in wasted Malawian adults with HIV who were starting antiretroviral therapy . Design R and omised , investigator blinded , controlled trial . Setting Large , public clinic associated with a referral hospital in Blantyre , Malawi . Participants 491 adults with BMI < 18.5 . Interventions Ready-to-use fortified spread ( n=245 ) or corn-soy blend ( n=246 ) . Main outcome measures Primary outcomes : changes in BMI and fat-free body mass after 3.5 months . Secondary outcomes : survival , CD4 count , HIV viral load , quality of life , and adherence to antiretroviral therapy . Results The mean BMI at enrolment was 16.5 . After 14 weeks , patients receiving fortified spread had a greater increase in BMI and fat-free body mass than those receiving corn-soy blend : 2.2 ( SD 1.9 ) v 1.7 ( SD 1.6 ) ( difference 0.5 , 95 % confidence interval 0.2 to 0.8 ) , and 2.9 ( SD 3.2 ) v 2.2 ( SD 3.0 ) kg ( difference 0.7 kg , 0.2 to 1.2 kg ) , respectively . The mortality rate was 27 % for those receiving fortified spread and 26 % for those receiving corn-soy blend . No significant differences in the CD4 count , HIV viral load , assessment of quality of life , or adherence to antiretroviral therapy were noted between the two groups . Conclusion Supplementary feeding with fortified spread result ed in a greater increase in BMI and lean body mass than feeding with corn-soy blend . Trial registration Current Controlled Trials IS RCT N67515515 In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Objective : There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy ( ART ) . This study tested the efficacy of short message service ( SMS ) reminders on adherence to ART among patients attending a rural clinic in Kenya . Design : A r and omized controlled trial of four SMS reminder interventions with 48 weeks of follow-up . Methods : Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and r and omly assigned to a control group or one of the four intervention groups . Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency . Adherence was measured using the medication event monitoring system . The primary outcome was whether adherence exceeded 90 % during each 12-week period of analysis and the 48-week study period . The secondary outcome was whether there were treatment interruptions lasting at least 48 h. Results : In intention-to-treat analysis , 53 % of participants receiving weekly SMS reminders achieved adherence of at least 90 % during the 48 weeks of the study , compared with 40 % of participants in the control group ( P = 0.03 ) . Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group ( 81 vs. 90 % , P = 0.03 ) . Conclusion : These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in re source -limited setting Objective : To assess the efficacy of a peer-delivered intervention to promote short-term ( 6-month ) and long-term ( 12-month ) adherence to HAART in a Mozambican clinic population . Design : A 2-arm r and omized controlled trial was conducted between October 2004 and June 2006 . Participants : Of 350 men and women ( ≥18 years ) initiating HAART , 53.7 % were female , and 97 % were on 1 fixed-dose combination pill twice a day . Intervention : Participants were r and omly assigned to receive 6 weeks ( Monday through Friday ; 30 daily visits ) of peer-delivered , modified directly observed therapy ( mDOT ) or st and ard care . Peers provided education about treatment and adherence and sought to identify and mitigate adherence barriers . Outcome : Participants ' self-reported medication adherence was assessed 6 months and 12 months after starting HAART . Adherence was defined as the proportion of prescribed doses taken over the previous 7 days . Statistical analyses were performed using intention-to-treat ( missing = failure ) . Results : Intervention participants , compared to those in st and ard care , showed significantly higher mean medication adherence at 6 months ( 92.7 % vs. 84.9 % , difference 7.8 , 95 % confidence interval [ CI ] : 0.0.02 , 13.0 ) and 12 months ( 94.4 % vs. 87.7 % , difference 6.8 , 95 % CI : 0.9 , 12.9 ) . There were no between-arm differences in chart- abstract ed CD4 counts . Conclusions : A peer-delivered mDOT program may be an effective strategy to promote long-term adherence among persons initiating HAART in re source -poor setting This study examined whether a self-management intervention based on feedback of adherence performance and principles of social cognitive theory improves adherence to antiretroviral dosing schedules . Forty-three individuals with HIV/AIDS who were starting or switching to a new protease inhibitor regimen were r and omly assigned to be in a medication self-management program or usual care control group . The self-management program included skills development exercises , three monthly visits for medication consultations , and monthly feedback of adherence performance using electronic monitors on medication bottles . Participants also completed a 40-item question naire that measured self-efficacy to take medications , on schedule , in a variety of situations . Logistic regression analysis indicated that individuals in the self-management group were significantly more likely to take 80 % or more of their doses each week than individuals in the control group ( n=29 , OR=7.8 , 95 % CI=2.2 - 28.1 ) . Self-management training with feedback of adherence performance is a potentially useful model for improving adherence to complex regimens in HIV/AIDS care BACKGROUND Exp and ed access to combination antiretroviral therapy ( ART ) in re source -poor setting s is dependent on task shifting from doctors to other health-care providers . We compared outcomes of nurse versus doctor management of ART care for HIV-infected patients . METHODS This r and omised non-inferiority trial was undertaken at two South African primary -care clinics . HIV-positive individuals with a CD4 cell count of less than 350 cells per microL or WHO stage 3 or 4 disease were r and omly assigned to nurse-monitored or doctor-monitored ART care . Patients were r and omly assigned by stratified permuted block r and omisation , and neither the patients nor those analysing the data were masked to assignment . The primary objective was a composite endpoint of treatment-limiting events , incorporating mortality , viral failure , treatment-limiting toxic effects , and adherence to visit schedule . Analysis was by intention to treat . Non-inferiority of the nurse versus doctor group for cumulative treatment failure was prespecified as an upper 95 % CI for the hazard ratio that was less than 1.40 . This study is registered with Clinical Trials.gov , number NCT00255840 . FINDINGS 408 patients were assigned to doctor-monitored ART care and 404 to nurse-monitored ART care ; all participants were analysed . 371 ( 46 % ) patients reached an endpoint of treatment failure : 192 ( 48 % ) in the nurse group and 179 ( 44 % ) in the doctor group . The hazard ratio for composite failure was 1.09 ( 95 % CI 0.89 - 1.33 ) , which was within the limits for non-inferiority . After a median follow-up of 120 weeks ( IQR 60 - 144 ) , deaths ( ten vs 11 ) , virological failures ( 44 vs 39 ) , toxicity failures ( 68 vs 66 ) , and programme losses ( 70 vs 63 ) were similar in nurse and doctor groups , respectively . INTERPRETATION Nurse-monitored ART is non-inferior to doctor-monitored therapy . Findings from this study lend support to task shifting to appropriately trained nurses for monitoring of ART . FUNDING National Institutes of Health ; United States Agency for International Development ; National Institute of Allergy and Infectious Diseases Improved therapeutic strategies , including the introduction of protease inhibitors , have led to a striking decrease in HIV-related morbidity and mortality ( 1 , 2 ) . It is widely believed that adherence to an antiretroviral regimen is central to the likelihood that a patient will derive sustained benefit from therapy ( 3 , 4 ) . Conventional wisdom holds that two groups of patients are currently experiencing clinical and virologic failure . The first group consists of patients who have received multiple different antiretroviral drugs over a prolonged period of time and who may be infected predominantly with HIV strains that are resistant to multiple drugs . The second group comprises patients who adhere poorly to their antiretroviral regimen . The two groups are not mutually exclusive : Patients with suboptimal adherence may be more likely to have antiretroviral drugresistant HIV infection . The potential public health importance of adherence to therapy in prevention of transmission of drug-resistant virus has also been emphasized ( 5 ) . Patients with suboptimal adherence to antiretroviral therapy and poor adherence to use of safer-sex practice s , such as use of condoms , may infect others with their own antiretroviral drugresistant virus . Anecdotal experience suggests that physicians may be unwilling to prescribe combination antiretroviral therapy to patients whom they perceive to be at high risk for poor adherence ( 6 ) . Given the critical importance of adherence to therapy to patient outcome , secondary prevention of HIV infection , and willingness of providers to prescribe therapy , we prospect ively investigated the association between protease inhibitor adherence and patient outcome , factors related to adherence , and the accuracy of physicians ' prediction of patient adherence . We used a microelectronic monitoring system to assess adherence to antiretroviral therapy . Methods Study Sample The study was conducted at the HIV clinics of the Veterans Affairs Medical Center , Pittsburgh , Pennsylvania , and University of Nebraska Medical Center , Omaha , Nebraska . The HIV physicians at these clinics were primary care providers for the study patients . Each site also had a dedicated HIV nurse coordinator . From August 1997 to March 1999 , we enrolled consecutive patients with HIV infection who were already receiving a protease inhibitor ( experienced patients ) or who were to begin taking a protease inhibitor ( naive patients ) . Exclusion criteria were inability to give informed written consent ; expectation of continued use of a medication organizer to include protease inhibitors ; and residence in a nursing home , jail , or hospice , where medications were dispensed at least daily . Collection of Baseline Data At baseline , a study investigator used medical chart review to complete a 52-item question naire for each patient . The question naire covered demographic information ( age , sex , ethnicity , risk factors for HIV infection , educational and employment status , income ) , medical history ( years known to be HIV infected ; opportunistic infections ; history of schizophrenia , depression , or bipolar affective disorder ) , and medication use ( name , dose , and frequency of all antiretroviral agents , other antimicrobials , and other prescription therapies ) . The enrolling physician assessed use of illegal drugs and nonprescription therapies ( including herbal or alternative therapies ) by interview . Alcohol abuse was assessed by using the CAGE question naire ( cutting down , annoyance with criticism , guilty feelings , and use of eye-opener drinks ) ( 7 ) . Information about use of adherence aids ( such as personal reminders by significant others or timers , alarms , or other devices ) was specifically sought . The investigator asked study patients if they felt that their current symptoms were attributable to HIV infection , the antiretroviral medications , or both . In addition , patients were asked whether they agreed with such health beliefs as Do you think your antiretroviral therapy will make you live longer ? At baseline , each patient completed the Beck Depression Inventory and the General Health Question naire ( 8 , 9 ) , well-vali date d measures of psychiatric morbidity that have been widely used in patients with HIV infection ( 9 - 11 ) . Patients completed the inventories as a written task without the assistance of a physician or clinic nurse . At baseline , we used the following question to elicit a prediction of adherence to protease inhibitor therapy from the patient 's primary HIV physician and clinic nurse : Do you think that the patient is compliant with antiretroviral therapy , that is , taking greater than 80 % of the prescribed doses of antiretroviral medications ? This prediction was made after collection of the baseline information but before actual measurement of adherence using the microelectronic monitoring system had begun . Collection of Follow-up Data Every 3 months for the duration of the study , the study participants were asked whether any of the following had changed since their previous visit : employment , use of alcohol or illegal drugs , residence , attribution of symptoms to the antiretroviral therapy or HIV infection , and changes in medications . Patients completed a new Beck Depression Inventory and General Health Question naire . The primary HIV physician determined whether the patient had developed an opportunistic infection in the past 3 months . Laboratory Testing At baseline and every 3 months for the duration of the study , HIV RNA levels were measured by using the Roche Amplicor System ( Roche Diagnostics , Nutley , New Jersey ) and CD4 lymphocyte sub population assays were performed . Assessment of Adherence Adherence was measured by using the Medication Events Monitoring System ( MEMS ) ( Aprex , Union City , California ) . The MEMS TrackCap system consists of st and ard medication bottles that have a pressure-activated microprocessor in the cap ( 12 ) . The microprocessor records each opening and lists the date , time , and duration of opening . The information on medication dosing is retrieved by scanning the cap over a purpose -built communicator module . The information is then stored in a data base provided by Aprex . Although the MEMS TrackCap system can not prove consumption of the drug by the patient , prolonged deception by patients has been shown to be unlikely ( 13 ) . Patients were provided with a MEMS TrackCap bottle for each prescribed protease inhibitor ( including refrigerated ritonavir capsules ) . Use of the MEMS TrackCaps system was not possible for patients who were prescribed ritonavir from August 1998 onward because ritonavir capsules were no longer available . The patients could use their regular medication organizer for all other medications . The caps were scanned each time the patient presented to the HIV clinic . Patients were specifically instructed not to take extra doses out at any time ( for example , not to take out an extra dose in the morning for consumption at lunchtime ) . Patients were offered small pill bottles that could be easily carried in a coat pocket . Adherence rates were defined as the number of doses recorded by the MEMS TrackCap divided by the total number of doses prescribed during the monitoring period . To evaluate the effect of dosing frequency on adherence , dosing interval errors were defined as medication doses taken at a time other than that prescribed ( that is,<9 hours or>15 hours after the previous dose of a medication prescribed every 12 hours or<5 hours or>11 hours after the previous dose of a medication prescribed every 8 hours ) ( 12 ) . Definitions of Virologic and Clinical Outcomes Virologic failure was defined as an HIV RNA level greater than 400 copies/mL at the last study visit . Changes in CD4 lymphocyte counts were calculated as the difference between the count at the baseline visit and the count at the final study visit . Opportunistic infections were defined according to Centers for Disease Control and Prevention criteria ( 14 ) . Hospitalization for all causes was recorded as the number of nights spent in any acute-care hospital ; nursing homes and drug or alcohol rehabilitation facilities were excluded . Mortality was defined as all-cause mortality at any time during the study period . Statistical Analysis All data was entered into a computerized data base , PROPHET Statistics Version 6.0 ( AB Tech Corp. , Charlottesville , Virginia ) . The chi-square or Fisher test was used to compare categorical variables . Continuous variables were examined by using the t-test or the MannWhitney test . Baseline and follow-up values were compared by using the paired t-test or the Wilcoxon signed-rank test . To examine the relation between two continuous measures , a best-fit line was obtained . The slope of this line was then tested against the null hypothesis of a slope of zero . The Pearson correlation coefficient was also calculated . Cox proportional-hazards regression was used to evaluate the relation between adherence and time to virologic failure . In the Cox model , predictor variables found to be significant ( P<0.1 ) in univariate analysis were added to the model . Logistic regression models were used to assess the effects of multiple variables on adherence . Factors were entered into the regression model if they were found by univariate analysis to be significantly associated ( P<0.1 ) . To analyze time to return of detectable HIV RNA for patients with an undetectable viral load at baseline , KaplanMeier survival curves were computed for less than 95 % adherence and 95 % or greater adherence and were compared by using the MantelCox test . The McNemar test was used to compare the predictions of the clinical nurses and physicians . Ethical Considerations The study was approved by the institutional review boards of the two study centers . Patients were fully informed that their adherence to protease inhibitor therapy was being measured by using the MEMS TrackCap system . Results Patient Characteristics Of 99 patients enrolled in the study , 6 withdrew before follow-up data were collected ( Objectives : To determine short- and long-term efficacy of modified directly observed therapy ( m-DOT ) on antiretroviral adherence . Design : R and omized controlled trial . Setting and Analytic Approach : From September 2003 to November 2004 , 234 HIV-infected adults were assigned m-DOT ( 24 weeks of twice weekly health center visits for nurse-observed pill ingestion , adherence support , and medication collection ) or st and ard care . Follow-up continued until week 72 . Self-reported and pill-count adherence and , secondarily , viral suppression and body mass index measures are reported . Generalized estimating equations adjusted for intraclient clustering and covariates were used . Results : During weeks 1 - 24 , 9.1 % ( 9/99 ) of m-DOT participants reported missing doses compared with 19.1 % ( 20/105 ) of controls ( P = 0.04 ) and 96.5 % ( 517/571 ) of m-DOT pill-count measures were ≥95 % compared with 86.1 % ( 445/517 ) in controls [ adjusted odds ratio = 4.4 ; 95 % confidence interval ( CI ) = 2.6 to 7.5 ; P < 0.001 . Adherence with m-DOT was 4.8 times greater ( 95 % CI = 2.7 to 8.6 ; P < 0.001 ) with adjustment for depression and HIV-related hospitalization . In weeks 25 - 48 , adherence with m-DOT ( 488/589 ) was similar to controls ( 507/630 ) . Viral suppression at 48 weeks was 2.0 times ( 95 % CI = 0.8 to 5.2 ; P = 0.13 ) as likely in m-DOT participants as controls . M-DOT patients had larger body mass index increases at 24 weeks ( 2.2 vs 1.4 kg/m3 ; P = 0.014 ) . Viral suppression was more likely at week 48 ( 21/25 vs 13/22 ; P = 0.057 ) and week 72 ( 27/30 vs 15/23 ; P = 0.027 ) among depressed participants receiving m-DOT . Conclusions : M-DOT increased adherence , most notably among depressed participants Objective : To evaluate the efficacy of a program design ed to improve adherence to antiretroviral therapy among patients with poor adherence . Methods : A r and omized intervention trial was conducted among 90 HIV-positive patients experiencing treatment failure as a result of noncompliance with their medication regimen . Eligible participants were r and omly assigned to an adherence case management intervention with monetary reinforcement ( CM ) or to a st and ard of care group ( SC ) . The CM participants met regularly with a treatment advocate for individualized adherence support . Efficacy was measured in terms of reductions in viral load and improvements in immune function at weeks 12 , 24 , and 48 . Results : After 48 weeks , 55 % ( n = 26 ) of those in the CM achieved at least a 1-log10 drop in viral load as compared to 28 % ( n = 12 ) in the SC group ( P = .0089 ) . Furthermore , the mean CD4 count was 209 cells/mm3 for the CM group as compared to 150 cells/mm3 in the SC group ( P = .0333 ) . Based on logistic regression analysis , being in the CM was an independent predictor of reduction in viral load ( odds ratio = 2.49 ; P = .0514 ) . Conclusion : The individualized adherence intervention is feasible and effective in reducing viral load and improving immune function BACKGROUND A r and omized , controlled trial was conducted to evaluate the impact of a directly administered antiretroviral therapy program ( DAART ) and intensive adherence case management ( IACM ) intervention on virologic and immunologic response to highly active antiretroviral therapy ( HAART ) among patients at 3 public human immunodeficiency virus clinics in Los Angeles County , California . METHODS Participants included 250 treatment-naive and treatment-experienced persons for whom no more than 1 prior HAART regimen had failed . Five days per week for 6 months , a community worker delivered 1 HAART dose to DAART participants and observed the participant take it . IACM participants met weekly with a case manager to overcome barriers to HAART adherence . A control group ( the st and ard of care [ SOC ] group ) received the usual care . RESULTS The majority of patients were Latino ( 64 % ) or African American ( 24 % ) ; 57 % were monolingual Spanish speakers . Seventy-five percent of the patients were male , and 64 % reported an annual income of < 10,000 dollars . In an intent-to-treat analysis , no statistical differences were observed in the percentage of patients with an undetectable viral load ( i.e. , < 400 copies/mL ) at 6 months between the DAART group ( 54 % ) , IACM group ( 60 % ) , and SOC group ( 54 % ; P>.05 ) . An on-treatment analysis determined that there were no statistical differences in the percentage of patients with an undetectable viral load at 6 months between the DAART group ( 71 % ) , IACM group ( 80 % ) , and SOC group ( 74 % ; P>.05 ) . Additionally , there were no statistical differences in 6-month changes in the CD4 + cell count or in self-reported adherence to therapy . CONCLUSIONS Among patients with limited prior HAART experience and adherence barriers that had not been assessed before r and omization , no differences were found in virologic or immunologic response for DAART or IACM , compared with SOC , at 6 months . DAART and IACM did not improve short-term outcomes when SOC included other means of adherence support that were not controlled for by the study design Objective : To examine the independent association of discordant virologic and immunologic responses to highly active antiretroviral therapy ( HAART ) with mortality . Methods : A population -based study of 1527 treatment-naive individuals initiating HAART used Cox proportional hazards modeling to determine the independent association of treatment response at 3 to 9 months with nonaccidental mortality . Logistic regression was used to examine associations with discordant responses . Results : Viral load (VL)+/CD4− discordant responses were seen in 235 ( 15.4 % ) of subjects , and VL−/CD4 + responses were seen in 179 ( 11.7 % ) of subjects . In adjusted Cox regression models , discordant responses were found to be independently associated with an increased risk of mortality ( VL+/CD4− : relative hazard [ RH ] = 1.87 , 95 % confidence interval [ CI ] : 1.15 to 3.04 ; VL−/CD4 + : RH = 2.47 , 95 % CI : 1.54 to 3.95 ) . VL+/CD4− discordance was found to be associated with increasing age , baseline HIV RNA load < 100,000 copies/mL , baseline CD4 counts < 50 cells/μL , the use of lamivudine (3TC)/zidovudine ( ZDV ) , and poor adherence to therapy . VL−/CD4 + discordance was associated with younger age ; injection drug use ; baseline HIV RNA load > 100,000 copies/mL ; the use of 3TC/ZDV , didanosine (ddI)/3TC , or ddI/stavudine ; and poor adherence to therapy . Conclusion : Discordant responses are independently associated with an increased risk of mortality and are , in turn , associated with poor adherence to therapy This study examines the use of various direct observation therapy-HAART treatment support modalities in Jos , Nigeria . A 12-month observational study enrolling 175 antiretroviral naïve patients into four arms of direct observation therapy-HAART ( highly active antiretroviral therapy ) ; daily observed therapy ( DOT ) , twice weekly observed therapy ( TWOT ) , weekly observed therapy ( WOT ) and self-administered therapy ( SAT ) , examined community treatment support using family and community members . Treatment outcomes were much better in the treatment-supported groups compared with the control self-therapy group . CD4 cell increases were 218/μL ( DOT ) , 267/μL ( TWOT ) , 205/μL ( WOT ) versus 224/μL ( SAT ) , whereas plasma HIV-1 RNA reached undetectable levels ( < 400 copies/mL ) in 91 % , 88 % , 84 % versus 79 % of patients in the DOT , TWOT , WOT versus SAT groups , respectively , at 48 weeks . We , therefore , strongly support the use of treatment support in our setting Background : South Africa has the world ’s fastest growing AIDS epidemic . There is an urgent need for effective HIV risk reduction interventions in South Africa . Objective : The objective of this study was to develop and test the potential efficacy of a brief theory-based HIV prevention counseling intervention for sexually transmitted infection ( STI ) clinic patients in South Africa . Method : STI clinic patients in Cape Town ( N = 228 ) were assessed at baseline and r and omized to receive either : 1 ) a single 60-minute session motivational/skills-building HIV risk reduction counseling intervention or 2 ) a 20-minute HIV information/education session . Participants completed 1- and 3-month follow ups with 80 % retention . Results : The 60-minute motivational/skills risk reduction counseling demonstrated significantly greater risk reduction practice s , lower rates of unprotected intercourse , and greater likelihood of receiving HIV testing after the intervention . Conclusions : Brief theory-based HIV prevention counseling may significantly reduce HIV risk behaviors for STI clinic patients in South Africa BACKGROUND Mobile ( cell ) phone communication has been suggested as a method to improve delivery of health services . However , data on the effects of mobile health technology on patient outcomes in re source -limited setting s are limited . We aim ed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load . METHODS WelTel Kenya1 was a multisite r and omised clinical trial of HIV-infected adults initiating antiretroviral therapy ( ART ) in three clinics in Kenya . Patients were r and omised ( 1:1 ) by simple r and omisation with a r and om number generating program to a mobile phone short message service ( SMS ) intervention or st and ard care . Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. R and omisation , laboratory assays , and analyses were done by investigators masked to treatment allocation ; however , study participants and clinic staff were not masked to treatment . Primary outcomes were self-reported ART adherence ( > 95 % of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits ) and plasma HIV-1 viral RNA load suppression ( < 400 copies per mL ) at 12 months . The primary analysis was by intention to treat . This trial is registered with Clinical Trials.gov , NCT00830622 . FINDINGS Between May , 2007 , and October , 2008 , we r and omly assigned 538 participants to the SMS intervention ( n=273 ) or to st and ard care ( n=265 ) . Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group ( relative risk [ RR ] for non-adherence 0·81 , 95 % CI 0·69 - 0·94 ; p=0·006 ) . Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group , ( RR for virologic failure 0·84 , 95 % CI 0·71 - 0·99 ; p=0·04 ) . The number needed to treat ( NNT ) to achieve greater than 95 % adherence was nine ( 95 % CI 5·0 - 29·5 ) and the NNT to achieve viral load suppression was 11 ( 5·8 - 227·3 ) . INTERPRETATION Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals . Mobile phones might be effective tools to improve patient outcome in re source -limited setting s. FUNDING US President 's Emergency Plan for AIDS Relief Objective To examine the relationship between adherence , viral suppression and antiretroviral resistance in HIV-infected homeless and marginally housed people on protease inhibitor ( PI ) therapy . Design and setting A cross-sectional analysis of subjects in an observational prospect i ve cohort systematic ally sample d from free meal lines , homeless shelters and low-income , single-room occupancy ( SRO ) hotels . Participants Thirty-four HIV-infected people with a median of 12 months of PI therapy . Main outcomes Adherence measured by periodic unannounced pill counts , electronic medication monitoring , and self-report ; HIV RNA viral load ; and HIV-1 genotypic changes associated with drug resistance . Results Median adherence was 89 , 73 , and 67 % by self-report , pill count , and electronic medication monitor , respectively . Thirty-eight per cent of the population had over 90 % adherence by pill count . Depending on the measure , adherence explained 36–65 % of the variation in concurrent HIV RNA levels . The three adherence measures were closely related . Of 20 genotyped patients who received a new reverse transcriptase inhibitor ( RTI ) when starting a PI , three had primary protease gene substitutions . Of 12 genotyped patients who received a PI without a new RTI , six had primary protease gene substitutions ( P < 0.03 ) . Conclusion A substantial proportion of homeless and marginally housed individuals had good adherence to PI therapy . A strong relationship was found between independent methods of measuring adherence and concurrent viral suppression . PI resistance was more closely related to the failure to change RTI when starting a PI than to the level of adherence Background : The observation that extremely high levels of medication adherence are required to achieve complete virologic suppression is based largely on studies of treatment-experienced patients receiving HIV protease inhibitor (PI)-based therapy without ritonavir boosting . This study aims to define the level of adherence needed to achieve virologic suppression in patients receiving boosted PI-based highly active antiretroviral therapy ( HAART ) with lopinavir/ritonavir . Methods : HIV-infected adults receiving a regimen containing lopinavir/ritonavir were recruited into a prospect i ve , observational study of the relation between adherence to lopinavir/ritonavir and virologic outcomes . Adherence was measured using the Medication Event Monitoring System ( MEMS ; Aardex , Union City , CA ) . HIV-1 viral load ( VL ) was measured at week 24 . Results : The final study population contained 64 subjects . Eighty percent had AIDS , 97 % received lopinavir/ritonavir before enrollment , and most had more than 7 years of HAART experience . Mean adherence overall was 73 % . Eighty percent and 59 % achieved a VL < 400 copies/mL and a VL < 75 copies/mL , respectively . Mean adherence was 75 % in those achieving a VL < 75 copies/mL. High rates of virologic suppression were observed in all adherence quartiles , including the lowest quartile ( range of adherence : 23.5%-53.3 % ) . Conclusions : Moderate levels of adherence can lead to virologic suppression in most patients taking lopinavir/ritonavir-based HAART Background : Directly observed therapy ( DOT ) for antiretroviral therapy ( ART ) may improve adherence , but there are limited data on its clinical effectiveness . Methods : Adult patients initiating ART in a public clinic in Cape Town , South Africa , were r and omized to treatment-supporter DOT-ART or self-administered ART . DOT-ART patients and supporters received baseline and follow-up training and monitoring . The primary endpoints were the proportions of patients with HIV viral load less than 400 copies/ml and change in CD4 cell counts at 12 and 24 months . Results : Two hundred and seventy-four patients enrolled ( 137 in each arm ) and baseline characteristics were similar for both arms . The study was stopped early for futility by an independent Data and Safety Monitoring Board . In an intention-to-treat analysis , the proportions of patients with viral load less than 400 copies/ml at 12 months were 72.8 % in the DOT-ART arm and 68.4 % in the Self-ART arm ( P = 0.42 ) . DOT-ART patients had greater median CD4 cell count ( cells/μl ) increases at 6 months [ 148 ( IQR 84–222 ) vs. 111 ( IQR 44–196 ) P = 0.02 ] but similar results at all other time-points . Survival was significantly better in the DOT-ART arm ( 9 deaths , 6.6 % ) than in the Self-ART arm ( 20 deaths , 14.6 % ; log-rank P = 0.02 ) . In Cox regression analysis , mortality was independently associated with study arm [ DOT vs. self-ART ; HR 0.38 , 95 % confidence interval ( CI ) 0.17–0.86 ] . Conclusion : DOT-ART showed no effect on virologic outcomes but was associated with greater CD4 cell count increases at 6-month follow-up . Survival was significantly better for DOT-ART compared to Self-ART , but this was not explained by improved virologic or immunologic outcomes BACKGROUND The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 ( HIV-1 ) infection are not clear . We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine . METHODS A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count ( 50 or fewer vs. 51 to 200 cells per cubic millimeter ) and r and omly assigned to one of two daily regimens : 600 mg of zidovudine ( or stavudine ) and 300 mg of lamivudine , or that regimen with 2400 mg of indinavir . The primary end point was the time to the development of the acquired immunodeficiency syndrome ( AIDS ) or death . RESULTS The proportion of patients whose disease progressed to AIDS or death was lower with indinavir , zidovudine , and lamivudine ( 6 percent ) than with zidovudine and lamivudine alone ( 11 percent ; estimated hazard ratio , 0.50 ; 95 percent confidence interval , 0.33 to 0.76 ; P=0.001 ) . Mortality in the two groups was 1.4 percent and 3.1 percent , respectively ( estimated hazard ratio , 0.43 ; 95 percent confidence interval , 0.19 to 0.99 ; P=0.04 ) . The effects of treatment were similar in both CD4 cell strata . The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results . CONCLUSIONS Treatment with indinavir , zidovudine , and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine OBJECTIVE To evaluate various strategies aim ed at improving adherence to antiretroviral therapy ( ART ) . METHODS Patients initiated on ART at Muhimbili National Hospital HIV clinic were r and omly assigned to either regular adherence counseling , regular counseling plus a calendar , or regular counseling and a treatment assistant . Patients were seen monthly ; during these meetings self-reported adherence to treatment was recorded . Disease progression was monitored clinical ly and immunologically . RESULTS Of the 621 patients r and omized , 312 received regular counseling only , 242 regular counseling and calendars , while 67 had treatment assistants in addition to regular counseling . The mean ( SD ) follow-up time was 14.5 ( 4.6 ) months . During follow-up 20 ( 3.2 % ) patients died , and 102 ( 16.4 % ) were lost to follow-up ; this was similar in all groups . In 94.8 % of all visits , patients reported to have adhered to treatment . In only 39 ( 0.7 % ) visits did patients report a < or = 95 % adherence . There were no differences in adherence ( P = 0.573 ) or differences in CD4 count and weight changes over time in the interventions . CONCLUSIONS Good adherence to ART is possible in re source constrained countries . Persistent adherence counseling in clinic setting s by itself may be effective in improving adherence to ART OBJECTIVE To evaluate cognitive-behavioral therapy to enhance medication adherence and reduce depression ( CBT-AD ) in individuals with HIV . DESIGN A two arm , r and omized , controlled , cross-over trial comparing CBT-AD to enhanced treatment as usual only ( ETAU ) . ETAU , which both groups received , included a single-session intervention for adherence and a letter to the patient 's provider documenting her or his continued depression . The intervention group also received 10 to 12 sessions of CBT-AD . MAIN OUTCOME MEASURES Adherence to antiretroviral therapy as assessed by Medication Event Monitoring Systems ( MEMs ) and depression as assessed by blinded structured evaluation . RESULTS At the acute outcome assessment ( 3-months ) , those who received CBT-AD evidence d significantly greater improvements in medication adherence and depression relative to the comparison group . Those who were originally assigned to the comparison group who chose to cross over to CBT-AD showed similar improvements in both depression and adherence outcomes . Treatment gains for those in the intervention group were generally maintained at 6- and 12-month follow-up assessment s. By the end of the follow-up period , those originally assigned CBT-AD demonstrated improvements in plasma HIV RNA concentrations , though these differences did not emerge before the cross-over , and hence there were not between-groups differences . CONCLUSIONS CBT-AD is a potentially efficacious approach for individuals with HIV struggling with depression and adherence . Replication and extension in larger efficacy trials are needed Background : The provision of food supplementation to food-insecure patients initiating antiretroviral therapy ( ART ) may improve adherence to medications . Methods : A home-based adherence support program at 8 government clinics assessed patients for food insecurity . Four clinics provided food supplementation , and 4 acted as controls . The analysis compared adherence ( assessed by medication possession ratio ) , CD4 , and weight gain outcomes among food-insecure patients enrolled at the food clinics with those enrolled at the control clinics . Results : Between May 1 , 2004 , and March 31 , 2005 , 636 food- insecure adults were enrolled . Food supplementation was associated with better adherence to therapy . Two hundred fifty-eight of 366 ( 70 % ) patients in the food group achieved a medication possession ratio of 95 % or greater versus 79 of 166 ( 48 % ) among controls ( relative risk = 1.5 ; 95 % confidence interval : 1.2 to 1.8 ) . This finding was unchanged after adjustment for sex , age , baseline CD4 count , baseline World Health Organization stage , and baseline hemoglobin . We did not observe a significant effect of food supplementation on weight gain or CD4 cell response . Conclusions : This analysis suggests that providing food to food-insecure patients initiating ART is feasible and may improve adherence to medication . A large r and omized study of the clinical benefits of food supplementation to ART patients is urgently needed to inform international policy BACKGROUND The efficacy of triple-drug antiretroviral regimens in the treatment of patients infected with HIV has been established in several r and omized clinical trials . However , the effectiveness of these new regimens in patient population s outside clinical trials remain unproven . This study compared mortality and AIDS-free survival among HIV-infected patients in British Columbia who were treated with double- and triple-drug regimens . METHODS The authors used a prospect i ve , population -based cohort design to study a population of HIV-positive men and women 18 years or older for whom antiretroviral therapy was first prescribed between Oct. 1 , 1994 , and Dec. 31 , 1996 ; all patients were from British Columbia . Rates of progression from the initiation of antiretroviral therapy to death or to diagnosis of primary AIDS were determined for patients who initially received an ERA-II regimen ( 2 nucleoside analogue reverse transcriptase inhibitors [ NRTIs ] including lamivudine or stavudine , or both ) and for those who initially received an ERA-III regimen ( triple-drug regimen consisting of 2 NRTIs and a protease inhibitor [ indinavir , ritonavir or saquinavir ] or a non-NRTI [ nevirapine ] ) . RESULTS A total of 500 men and women ( 312 receiving an ERA-III regimen and 188 an ERA-III regimen ) were eligible . Patients in the ERA-III group survived significantly longer than those in the ERA-II group . As of Dec. 31 , 1997 , 40 patients had died ( 35 in the ERA-II group and 5 in the ERA-III group ) , for a crude mortality rate of 8.0 % . The cumulative mortality rates at 12 months were 7.4 % ( 95 % confidence interval [ CI ] 5.9 % to 8.9 % ) for patients in the ERA-II group and 1.6 % ( 95 % CI 0.7 % to 2.5 % ) for those in the ERA-III group ( log rank p = 0.003 ) . The likelihood of death was more than 3 times higher among patients in the ERA-II group ( mortality risk ratio 3.82 [ 95 % CI 1.48 % to 9.84 ] , p = 0.006 ) . After adjustment for prophylaxis for Pneumocystis carinii pneumonia or Mycobacterium avium infection , AIDS diagnosis , CD4 + cell count , sex and age at initiation of therapy , the likelihood of death among patients in the ERA-II group was 3.21 times higher ( 95 % CI 1.24 to 8.30 , p = 0.016 ) than in the ERA-III group . Cumulative rates of progression to AIDS or death at 12 months were 9.6 % ( 95 % CI 7.7 % to 11.5 % ) in the ERA-II group and 3.3 % ( 95 % CI 1.8 % to 4.8 % ) in the ERA-III group ( log rank p = 0.006 ) . After adjustment for prognostic variables ( prophylaxis for P. carinii pneumonia or M. avium infection , CD4 + cell count , sex and age at initiation of treatment ) , the likelihood of progression to AIDS or death at 12 months among patients in the ERA-II group was 2.37 times higher ( 95 % CI 1.04 to 5.38 , p = 0.040 ) than in the ERA-III group . INTERPRETATION This population -based cohort study confirms that patients initially treated with a triple-drug antiretroviral regimen comprising 2 NRTIs plus protease inhibitor or a non-NRTI have a lower risk of morbidity and death than patients treated exclusively with 2 NRTIs A small pilot trial of a multicomponent ( behavioral strategies , simplified patient information , and social support ) and multidisciplinary ( cognitive-behavioral therapy and nursing ) medication adherence intervention was conducted for HIV-infected adults prescribed antiretrovirals . Patients ( N = 33 ) were r and omly assigned to the intervention condition or st and ard care . Compared to the control group , patients in the intervention condition had significantly higher self-efficacy to communicate with clinic staff ( p = .04 ) and to continue treatment ( p = .04 ) , were significantly more likely to be using behavioral and cognitive strategies ( p = .01 and p = .04 ) , reported significantly higher life satisfaction ( p = .03 ) , reported significantly increased feelings of social support ( p = .04 ) , and showed a trend toward an increase in taking their medications on schedule ( p = .06 ) . The intervention , however , did not appear to affect health-related anxiety or to significantly improve adherence to dose . Implication s for future intervention planning are discussed Objective To determine plasma concentration ratio limits ( CORALS ) for HIV-protease inhibitors outside of which r and om plasma concentrations reflect partial compliance or noncompliance . In the absence of a gold st and ard for measuring compliance and to avoid complex techniques , measuring plasma concentrations may be an objective and easy way to check noncompliance . Methods Pharmacokinetic curves after observed ingestion were recorded in patients on steady-state indinavir 800 mg TID ( n = 22 ) , ritonavir 400 mg/saquinavir 400 mg BID ( n = 22 , ritonavir ; n = 17 , saquinavir hard-gel capsules ) , or nelfinavir 750 mg TID ( n = 4 ) or 1250 mg BID ( n = 4 ) . Concentration ratios were calculated by dividing the measured concentration by the median population value at the corresponding sampling time . Limits were based on the minimum P05 ( 5th percentile ) and maximum P95 of these ratios found during the sampling interval . With these limits the authors determined ( 1 ) the proportion of patients falsely judged as noncompliers after observed ingestion , ( 2 ) discrimination between compliers and noncompliers , and ( 3 ) the absolute percentage of noncompliers . To judge the last two elements , two sets of r and om plasma sample s were included : ( 1 ) sample s sent in by the physician on suspicion of noncompliance ( indinavir , n = 42 ; nelfinavir , n = 22 ; ) or from a study population stating imperfect compliance in a question naire ( ritonavir/saquinavir , n = 11 ) ; ( 2 ) control sample s sent in routinely for monitoring therapeutic levels ( indinavir , n = 41 ; nelfinavir , n = 201 ) or drawn from patients who stated perfect compliance in the question naire ( ritonavir/saquinavir , n = 35 ) . Results The following CORALS were found : indinavir < 0.23 or > 3.3 ; nelfinavir < 0.36 or > 2.1 ; ritonavir < 0.18 or > 1.9 ; saquinavir < 0.28 or > 2.3 . In 31 % to 55 % of the patients suspected of noncompliance a plasma concentration ratio outside these limits was found . If a ratio was outside the limits , there was a 68 % to 88 % chance that that plasma sample belonged to a patient suspected of noncompliance , compared with the controls ( all Chi-squared tests P < 0.05 ) . Compared with observed ingestion , these chances ranged from 87 % to 92 % . Conclusion By using concentration ratio limits ( CORALS ) , plasma sample s of protease inhibitors with values outside these limits are highly indicative of partial or noncompliance Background : Although adherence to antiretroviral therapy may be higher in sub-Saharan Africa , knowledge regarding the magnitude of adherence needed to maintain virological suppression in this setting is limited . Methods : A case-control study among HIV-infected individuals initiating highly active antiretroviral therapy ( HAART ) in Gaborone , Botswana , was performed . Cases were r and omly selected from subjects on HAART ≥6 months with plasma HIV-1 RNA levels ( viral loads ) > 1000 copies/mL. Controls were r and omly selected from subjects on HAART ≥6 months with all viral loads < 400 copies/mL. HAART adherence was determined using pharmacy refill records . Results : In total , 302 individuals were included ; 57 cases were compared with 245 controls with respect to adherence levels on nonnucleoside reverse transcriptase inhibitor-based HAART . Median adherence levels , as measured using pharmacy refill patterns , were consistently high but differed among cases and controls ( 91 % , interquartile range 83%-97 % for cases vs 97 % , interquartile range 91%-100 % for controls , P < 0.001 , rank-sum test ) . Adherence < 95 % was independently associated with virological failure ( odds ratio 4.19 , 95 % confidence interval 2.2 to 8.3 ) . Conclusions : Very high rates of adherence were present in this setting , yet virological failure occurred nonetheless . Future work should explore other factors that might explain treatment failure in the setting of high levels of adherence Loss to follow-up is problematic in most cohort studies and often leads to bias . Although guidelines suggest acceptable follow-up rates , the authors are unaware of studies that test the validity of these recommendations . The objective of this study was to determine whether the recommended follow-up thresholds of 60–80 % are associated with biased effects in cohort studies . A simulation study was conducted using 1000 computer replications of a cohort of 500 observations . The logistic regression model included a binary exposure and three confounders . Varied correlation structures of the data represented various levels of confounding . Differing levels of loss to follow-up were generated through three mechanisms : missing completely at r and om ( MCAR ) , missing at r and om ( MAR ) and missing not at r and om ( MNAR ) . The authors found no important bias with levels of loss that varied from 5 to 60 % when loss to follow-up was related to MCAR or MAR mechanisms . However , when observations were lost to follow-up based on a MNAR mechanism , the authors found seriously biased estimates of the odds ratios with low levels of loss to follow-up . Loss to follow-up in cohort studies rarely occurs r and omly . Therefore , when planning a cohort study , one should assume that loss to follow-up is MNAR and attempt to achieve the maximum follow-up rate possible We prospect ively studied long-term antiretroviral adherence patterns and their impact on biologic outcomes for human immunodeficiency virus (HIV)-infected participants in 2 r and omized , multicenter clinical trials . For the period from baseline to month 12 of the study , participants who reported adherence levels of 100 % , 80%-99 % , and 0%-79 % had plasma HIV RNA levels that decreased by 2.77 , 2.33 , and 0.67 log(10 ) copies/mL , respectively ( P<.001 ) , whereas their CD4 counts increased by 179 , 159 , and 53 cells/mm(3 ) , respectively ( P<.001 ) . Adherence predicted nondetectable HIV RNA levels ( < 50 copies/mL ) at 12 months of follow-up ( P<.001 ) . The HIV RNA level was nondetectable in 72 % of participants who reported 100 % adherence at all 4 follow-up visits , compared with 66 % , 41 % , 35 % , and 13 % of participants who reported 100 % adherence at 3 , 2 , 1 , or 0 follow-up visits , respectively ( P<.001 ) . Nonwhite race was associated with poorer adherence ( P<.001 ) , and older age was associated with better adherence ( P<.001 ) |
12,432 | 27,566,580 | HER2 amplification level is not a prognostic factor for HER2-positive breast cancer with trastuzumab-based targeted therapy in the clinical adjuvant setting | BACKGROUND Trastuzumab-based therapy is a st and ard , targeted treatment for HER2-positive breast cancer in the adjuvant setting .
However , patients do not benefit equally from it and the association between HER2 amplification level and patients ' survival remains controversial . | BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . Purpose : To assess pathologic complete response ( pCR ) , clinical response , feasibility , safety , and potential predictors of response to preoperative trastuzumab plus vinorelbine in patients with operable , human epidermal growth factor receptor 2 (HER2)–positive breast cancer . Experimental Design : Forty-eight patients received preoperative trastuzumab and vinorelbine weekly for 12 weeks . Single and multigene biomarker studies were done in an attempt to identify predictors of response . Results : Eight of 40 ( 20 % ) patients achieved pCR ( 95 % confidence interval , 9 - 36 % ) . Of 9 additional patients recruited for protocol -defined toxicity analysis , 8 were evaluable ; 42 of 48 ( 88 % ) patients had clinical response ( 16 patients , clinical complete response ; 26 patients , clinical partial response ) . T1 tumors more frequently exhibited clinical complete response ( P = 0.05 ) and showed a trend to exhibit pCR ( P = 0.07 ) . Five ( 13 % ) patients experienced grade 1 cardiac dysfunction during preoperative treatment . Neither HER2 nor estrogen receptor status changed significantly after exposure to trastuzumab and vinorelbine . RNA profiling identified three top-level clusters by unsupervised analysis . Tumors with extremes of response [ pCR ( n = 3 ) versus nonresponse ( n = 3 ) ] fell into separate groups by hierarchical clustering . No predictive genes were identified in pCR tumors . Nonresponding tumors were more likely to be T4 stage ( P = 0.02 ) and express basal markers ( P < 0.00001 ) , growth factors , and growth factor receptors . Insulin-like growth factor-I receptor membrane expression was associated with a lower response rate ( 50 % versus 97 % ; P = 0.001 ) . Conclusions : Preoperative trastuzumab plus vinorelbine is active and well tolerated in patients with HER2-positive , operable , stage II/III breast cancer . HER2-overexpressing tumors with a basal-like phenotype , or with expression of insulin-like growth factor-I receptor and other proteins involved in growth factor pathways , are more likely to be resistant to this regimen BACKGROUND It is unknown how a very high tumor total HER2 ( human epidermal growth factor receptor-2 ) content ( H2 T ) influences outcome in early breast cancer treated with adjuvant trastuzumab plus chemotherapy . PATIENTS AND METHODS H2 T was measured using a novel quantitative assay ( HERmark ( ® ) ) from formalin-fixed tumor tissue of 899 women who participated in the FinHer trial ( IS RCT N76560285 ) . In a chromogenic in situ hybridization ( CISH ) test , 197 ( 21.9 % ) patients had HER2-positive cancer and were r and omly assigned to receive trastuzumab or control . RESULTS Cancer H2 T levels varied 1808-fold . High H2 T levels were correlated with a positive HER2 status by CISH ( P < 0.0001 ) . A nonlinear association was present between H2 T and the hazard of distant recurrence in a sub population treatment effect pattern plot analysis in CISH-positive disease . Patients with very high H2 T ( defined by ≥22-fold the median of HER2-negative cancers ; 13 % of CISH-positive cancers ) did not benefit from adjuvant trastuzumab [ hazard ratio ( HR ) 1.23 ; 95 % confidence interval ( CI ) 0.33 - 4.62 ; P = 0.75 ] , whereas the rest of the patients with HER2-positive disease by CISH ( 87 % ) did benefit ( HR 0.52 ; 95 % CI 0.28 - 1.00 ; P = 0.050 ) . CONCLUSION Patients with HER2-positive breast cancer with very high tumor HER2 content may benefit less from adjuvant trastuzumab compared with those whose cancer has more moderate HER2 content PURPOSE To determine whether ( 1 ) immunohistochemical ( IHC ) HER2 status ( ie , 2 + or 3 + ) , ( 2 ) degree of fluorescence in situ hybridization ( FISH ) amplification according to ( 2a ) HER2/CEP17 ratio or ( 2b ) HER2 gene copy number , or ( 3 ) polysomy significantly influenced clinical outcome for patients with human epidermal growth factor receptor 2 ( HER2 ) -positive breast cancer enrolled in the Herceptin Adjuvant trial of trastuzumab versus no trastuzumab administered after completion of chemotherapy . PATIENTS AND METHODS IHC and /or FISH analyses were performed locally and required central confirmation as indicating HER2 positivity for trial entry . FISH data from the central HER2 analysis on patients in the 1-year trastuzumab and no trastuzumab arms were assessed in relation to disease-free survival ( DFS ) after a median 2 years of follow-up . RESULTS Central FISH results were available for 2,071 ( 61 % ) of the 3,401 patients r and omized to the 2 arms . Among patients with FISH-positive disease , ( 1 ) the hazard ratios for trastuzumab versus no trastuzumab were 0.56 ( 95 % CI , 0.32 to 0.99 ) for locally IHC2 + cases ( n = 340 ) and 0.80 ( 95 % CI , 0.40 to 1.61 ) for central ly IHC2 + cases ( n = 299 ) . There was no significant prognostic relationship between ( 2a ) HER2 FISH ratio , ( 2b ) HER2 copy number , or ( 3 ) polysomy and DFS in the control arm or predictive relationship defining differential benefit from trastuzumab . CONCLUSION There was no evidence for reduced benefit of trastuzumab in HER2 IHC2+FISH+ cases . The degree of HER2 amplification does not influence prognosis or benefit from adjuvant trastuzumab in patients treated with prior adjuvant chemotherapy BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy . RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation . We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P<0.0001 by the log-rank test , crossing the interim analysis boundary ) , representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points . Overall survival in the two groups was not significantly different ( 29 deaths with trastuzumab vs. 37 with observation ) . Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab . CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer . ( Clinical Trials.gov number , NCT00045032 . |
12,433 | 29,543,907 | Consumers preferred flavored e-cigarettes , and such preference varied with age groups and smoking status .
We also found that several flavors were associated with decreased harm perception while tobacco flavor was associated with increased harm perception .
In addition , some flavor chemicals and sweeteners used in e-cigarettes could be of toxicological concern .
Adolescents could consider flavor the most important factor trying e-cigarettes and were more likely to initiate vaping through flavored e-cigarettes .
Young adults overall preferred sweet , menthol , and cherry flavors , while non-smokers in particular preferred coffee and menthol flavors .
Adults in general also preferred sweet flavors ( though smokers like tobacco flavor the most ) and disliked flavors that elicit bitterness or harshness .
In terms of whether flavored e-cigarettes assisted quitting smoking , we found inconclusive evidence .
E-cigarette users likely initiated use with a cigarette like product and transitioned to an advanced system with more features .
Non-smokers and inexperienced e-cigarettes users tended to prefer no nicotine or low nicotine e-cigarettes while smokers and experienced e-cigarettes users preferred medium and high nicotine e-cigarettes .
Weak evidence exists regarding a positive interaction between menthol flavor and nicotine strength | OBJECTIVE Systematic review of research examining consumer preference for the main electronic cigarette ( e-cigarette ) attributes namely flavor , nicotine strength , and type . | Abstract Background : Awareness and use of electronic cigarettes ( e-cigs ) has increased significantly in the past five years , but little is known about the experiences , satisfaction , opinions and preferences of e-cigs users . Method : 1177 participants completed an online survey about their electronic cigarette preferences , of which 200 were r and omly selected for analysis . The data were analyzed using both qualitative and quantitative methods . Results : Participants found the design , the ability to customize , and the quality of vapour to be the most important characteristics of the device . Participants thought the most positive aspects of e-cig use were help to quit smoking , improved overall health , and reduced cost . The negative aspects associated with its use were mainly related to side effects , such as dry mouth . When asked to explain how e-cigs were used differently than cigarettes , participants reported puffing more regularly , but taking fewer puffs per session . Conclusions : Experienced e-cig users stated that initiating e-cig use helped them to quit or reduce their conventional smoking , which they believe reduced their health risks . In comparison to cigarette smoking , e-cig users reported using their e-cig more times per day , but with fewer puffs at each use time . Users acknowledged that more research is needed to underst and the safety and long-term effects of its use . They mentioned dry mouth as a common side effect and common problems with reliability of e-cigs . Underst and ing these views may help health professionals to assess and assist e-cig users , and in the future , may help regulators to improve quality and reduce risks BACKGROUND Few national surveys document the prevalence of e-cigarette use in the U.S. The existing metric to assess current use likely identifies individuals who have recently tried an e-cigarette but do not continue to use the product . PURPOSE To document the prevalence of e-cigarette ever use , current use , and established use in a nationally representative survey of current and former cigarette smokers in the U.S. METHODS A r and om sample of current and former cigarette smokers completed a web-based survey in June 2013 ( n=2,136 ) . Data were analyzed in November 2013 . Multivariate logistic regression identified demographic and smoking-related factors associated with each use category . Point estimates with 95 % CIs described e-cigarette use behaviors ( e.g. , preferred br and , purchasing patterns ) for each group . RESULTS Almost half of respondents had tried e-cigarettes ( 46.8 % ) , but prevalence of established use remained low ( 3.8 % ) . Although trial of e-cigarettes was highest among daily smokers , the odds of being an established e-cigarette user were greater for former smokers ( OR=3.24 , 95 % CI=1.13 , 9.30 , p<0.05 ) . Furthermore , e-cigarette preference and use patterns varied among ever , current , and established users . Established users reported using rechargeable e-cigarettes , having a regular br and , and using e-cigarettes at home and in the workplace at much higher levels than the " current use " metric captures . CONCLUSIONS Improved survey measures for e-cigarette use are needed . The identification of established e-cigarette users may provide insight to product features or other individual factors that are associated with sustained use of e-cigarettes Objectives : The objectives of this study were to assess the general public views and familiarity toward electronic cigarette ( e-cigarette ) in Kuantan , Malaysia . Methodology : A total of 277 Kuantan people were involved in this study . The question naire was distributed at r and om in shops , businesses , and public places in Kuantan . Statistical analysis was performed using SPSS ( version 17.0 ) . Results : From 400 participants , a total number of 277 ( 160 , 57.7 % men and 117 , 42.4 % women ) respondents completed the question naire . The mean age was 26.89 ± 9.8 years old . The majority of the study participants were male ( 57.7 % ) , Malay ( 83.8 % ) , Muslims ( 83.8 % ) , singles ( 69 % ) , and employed ( 75.8 % ) , with about 83 ( 29.9 % ) of the respondents were smokers . The prevalence of e-cigarettes smokers was found to be only 1.4 % ( n = 4 ) . About one-third of the respondents ( n = 72 , 26 % ) have tried e-cigarette before . Job status was significantly associated with smoking e-cigarette among the population ( P = 0.02 ) . Main factors for a person to start e-cigarette smoking were curiosity ( 37.5 % ) and cheaper price ( 40.8 % ) . Majority of respondents agreed that e-cigarette would not affect health as normal cigarette , and that variety of flavors contribute to better enjoyment ( 51.6 % and 66.7 % , respectively ) . Conclusion : The results of the current study demonstrate that the prevalence of e-cigarettes smoking and its popularity , familiarity , and knowledge are still insufficient among Kuantan population . Further studies should be done to tackle this problem before it getting worse Aims : Here , we present results from a prospect i ve pilot study that was aim ed at surveying changes in daily cigarette consumption in smokers making their first purchase at vape shops . Modifications in products purchase were also noted . Design : Participants were instructed how to charge , fill , activate and use their e-cigarettes ( e-cigs ) . Participants were encouraged to use these products in the anticipation of reducing the number of cig/day smoked . Setting s : Staff from LIAF contacted 10 vape shops in the province of the city of Catania ( Italy ) that acted as sponsors to the 2013 No Tobacco Day . Participants : 71 adult smokers ( ≥18 years old ) making their first purchase at local participating vape shops were asked by professional retail staff to complete a form . Measurements : Their cigarette consumption was followed-up prospect ively at 6 and 12 months . Details of products purchase ( i.e. , e-cigs hardware , e-liquid nicotine strengths and flavours ) were also noted . Findings : Retention rate was elevated , with 69 % of participants attending their final follow-up visit . At 12 month , 40.8 % subjects could be classified as quitters , 25.4 % as reducers and 33.8 % as failures . Switching from st and ard refillables ( initial choice ) to more advanced devices ( MODs ) was observed in this study ( from 8.5 % at baseline to 18.4 % at 12 month ) as well as a trend in decreasing the e-liquid nicotine strength , with more participants adopting low nicotine strength ( from 49.3 % at baseline to 57.1 % at 12 month ) . Conclusions : We have found that smokers purchasing e-cigarettes from vape shops with professional advice and support can achieve high success rates PURPOSE Electronic cigarettes ( e-cigarettes ) are a new type of device that delivers vaporized nicotine without the tobacco combustion of regular cigarettes . We sought to underst and awareness of and willingness to try e-cigarettes among adolescent males , a group that is at risk for smoking initiation and may use e-cigarettes as a " gateway " to smoking . METHODS A national sample of 11 - 19-year-old males ( n = 228 ) completed an online survey in November 2011 . We recruited participants through their parents , who were members of a panel of U.S. households constructed using r and om-digit dialing and addressed-based sampling . RESULTS Only two participants ( < 1 % ) had previously tried e-cigarettes . Among those who had not tried e-cigarettes , most ( 67 % ) had heard of them . Awareness was higher among older and non-Hispanic adolescents . Nearly 1 in 5 ( 18 % ) participants were willing to try either a plain or flavored e-cigarette , but willingness to try plain versus flavored varieties did not differ . Smokers were more willing to try any e-cigarette than nonsmokers ( 74 % vs. 13 % ; OR 10.25 , 95 % CI 2.88 , 36.46 ) . Nonsmokers who had more negative beliefs about the typical smoker were less willing to try e-cigarettes ( OR .58 , 95 % CI .43 , .79 ) . CONCLUSIONS Most adolescent males were aware of e-cigarettes , and a substantial minority were willing to try them . Given that even experimentation with e-cigarettes could lead to nicotine dependence and subsequent use of other tobacco products , regulatory and behavioral interventions are needed to prevent " gateway " use by adolescent nonsmokers . Campaigns promoting negative images of smokers or FDA bans on sales to youth may help deter use Background More US adolescents use e-cigarettes than smoke cigarettes . Research suggests flavoured e-cigarettes appeal to youth , but little is known about perceptions of and reasons for attraction to specific flavours . Methods A national sample of adolescents ( n=1125 ) ages 13–17 participated in a phone survey from November 2014 to June 2015 . We r and omly assigned adolescents to respond to survey items about 1 of 5 e-cigarette flavours ( tobacco , alcohol , menthol , c and y or fruit ) and used regression analysis to examine the impact of flavour on interest in trying e-cigarettes and harm beliefs . Results Adolescents were more likely to report interest in trying an e-cigarette offered by a friend if it were flavoured like menthol ( OR=4.00 , 95 % CI 1.46 to 10.97 ) , c and y ( OR=4.53 , 95 % CI 1.67 to 12.31 ) or fruit ( OR=6.49 , 95 % CI 2.48 to 17.01 ) compared with tobacco . Adolescents believed that fruit-flavoured e-cigarettes were less harmful to health than tobacco-flavoured e-cigarettes ( p<0.05 ) . Perceived harm mediated the relationship between some flavours and interest in trying e-cigarettes . A minority of adolescents believed that e-cigarettes did not have nicotine ( 14.6 % ) or did not know whether they had nicotine ( 3.6 % ) ; these beliefs did not vary by flavour . Discussion C and y-flavoured , fruit-flavoured and menthol-flavoured e-cigarettes appeal to adolescents more than tobacco-flavoured or alcohol-flavoured e-cigarettes . This appeal is only partially explained by beliefs about reduced harm . Given adolescents ' interest in trying e-cigarettes with certain flavours , policymakers should consider restricting advertisements promoting flavoured products in media that reach large numbers of young people . Future research should examine other reasons for the appeal of individual flavours , such as novelty and perceived luxury INTRODUCTION This study examined overall changes in nicotine concentrations when using a popular e-cigarette and 18 mg/mL nicotine e-Juice , and it further explored effects of sex and flavorings on these concentrations . METHODS We recruited nontreatment-seeking smokers who were willing to try e-cigarettes for 2 weeks and abstain from cigarette smoking . Subjects were r and omized to either menthol tobacco or non-menthol tobacco-flavored e-cigarette use for 7 - 10 days , and the next week they were crossed over to the other condition . On the last day of e-cigarette use of each flavor , subjects completed a laboratory session in which they used the e-cigarette for 5 min ad libitum . Nicotine concentrations were obtained 5 min before and 5 , 10 , 15 , 20 , and 30 min after the onset of e-cigarette use . RESULTS Twenty subjects completed at least 1 monitoring session . Nicotine concentrations significantly increased from baseline to 5 min by 4 ng/mL at the first laboratory session ( p < .01 ) and by 5.1 ng/mL at the second laboratory session ( p < .01 ) . Combining sessions , there were no main effects of sex or preferred flavor ( based on smoking history ) on changes in nicotine concentrations . After adding preferred flavor , sex , and visit order to the model , there was a significant preferred flavor by sex interaction ( p < .01 ) , such that women who received nonpreferred flavors had lower nicotine concentrations and rated their e-cigarette as less likeable ( p < .01 ) . CONCLUSION We found nicotine concentrations significantly increase after e-cigarette use for 5 min , and flavor may impact nicotine concentrations with e-cigarette use in women AIMS To ( 1 ) estimate predictors of first- versus second-generation electronic cigarette ( e-cigarette ) choice ; and ( 2 ) determine whether a second-generation device was ( i ) superior for reducing urge to smoke and withdrawal symptoms ( WS ) and ( ii ) associated with enhanced positive subjective effects . DESIGN Mixed-effects experimental design . Phase 1 : reason for e-cigarette choice was assessed via question naire . Phase 2 : participants were allocated r and omly to first- or second-generation e-cigarette condition . Urge to smoke and WS were measured before and 10 minutes after taking 10 e-cigarette puffs . SETTING University of East London , UK . PARTICIPANTS A total of 97 smokers ( mean age 26 ; st and ard deviation 8.7 ; 54 % female ) . MEASUREMENTS Single-item urge to smoke scale to assess craving and the Mood and Physical Symptoms Scale ( MPSS ) to assess WS . Subjective effects included : satisfaction , hit , ' felt like smoking ' and ' would use to stop smoking ' ( yes versus no response ) . FINDINGS Equal numbers chose each device , but none of the predictor variables ( gender , age , tobacco dependence , previous e-cigarette use ) accounted for choice . Only baseline urge to smoke/WS predicted urge to smoke/WS 10 minutes after use ( B = 0.38 ; P < 0.001 and B = 0.53 ; P < 0.001 ) . E-cigarette device was not a significant predictor . Those using the second-generation device were more likely to report satisfaction and use in a quit attempt ( χ(2 ) = 12.10 , P = 0.001 and χ(2 ) = 5.53 , P = 0.02 ) . CONCLUSIONS First- and second-generation electronic cigarettes appear to be similarly effective in reducing urges to smoke during abstinence , but second-generation devices appear to be more satisfying to users INTRODUCTION Product characteristics that impact e-cigarette appeal by altering the sensory experience of vaping need to be identified to formulate evidence -based regulatory policies . While products that contain sweet flavorings and produce a " throat hit " ( i.e. , desirable airway irritation putatively caused by nicotine ) are anecdotally cited as desirable reasons for vaping among young adults , experimental evidence of their impact on user appeal is lacking . This experiment applied a novel laboratory protocol to assess whether : ( 1 ) sweet flavorings and nicotine affect e-cigarette appeal ; ( 2 ) sweet flavorings increase perceived sweetness ; ( 3 ) nicotine increases throat hit ; and ( 4 ) perceived sweetness and throat hit are associated with appeal . METHODS Young adult vapers ( N=20 ; age 19 - 34 ) self-administered 20 st and ardized doses of aerosolized e-cigarette solutions varied according to a 3 flavor ( sweet [ e.g. , cotton c and y ] vs. non-sweet [ e.g. , tobacco-flavored ] vs. flavorless) × 2 nicotine ( 6mg/mL nicotine vs. 0mg/mL [ placebo ] ) double-blind , cross-over design . Participants rated appeal ( liking , willingness to use again and perceived monetary value ) , perceived sweetness and throat hit strength after each administration . RESULTS Sweet-flavored ( vs. non-sweet and flavorless ) solutions produced greater appeal and perceived sweetness ratings . Nicotine produced greater throat hit ratings than placebo , but did not significantly increase appeal nor interact with flavor effects on appeal . Controlling for flavor and nicotine , perceived sweetness was positively associated with appeal ratings ; throat hit was not positively associated with appeal . CONCLUSIONS Further identification of compounds in e-cigarette solutions that enhance sensory perceptions of sweetness , appeal , and utilization of e-cigarettes are warranted to inform evidence -based regulatory policies BACKGROUND Tobacco products containing menthol are widely used by youth . We used e-cigarettes to conduct an experimental evaluation of the independent and interactive effects of menthol and nicotine among youth . PROCEDURES Pilot chemosensory experiments with fourteen e-cigarette users identified low ( barely perceptible , 0.5 % ) and high ( similar to commercial e-liquid , 3.5 % ) menthol concentrations . Sixty e-cigarette users were r and omized to a nicotine concentration ( 0mg/ml , 6mg/ml , 12mg/ml ) and participated in 3 laboratory sessions . During each session , they received their assigned nicotine concentration , along with one of three menthol concentrations in r and om counterbalanced order across sessions ( 0 , 0.5 % , 3.5 % ) , and participated in three fixed-dose , and an ad-lib , puffing period . Urinary menthol glucuronide and salivary nicotine levels vali date d menthol and nicotine exposure . We examined changes in e-cigarette liking/wanting and taste , coolness , stimulant effects , nicotine withdrawal and ad-lib use . RESULTS Overall , the high concentration of menthol ( 3.5 % ) significantly increased e-cigarette liking/wanting relative to no menthol ( p<0.001 ) ; there was marginal evidence of nicotine * menthol interactions ( p=0.06 ) , with an increase in liking/wanting when 3.5 % menthol was combined with 12mg/ml nicotine , but not 6mg/ml nicotine . Importantly , both 0.5 % and 3.5 % menthol concentrations significantly improved taste and increased coolness . We did not observe nicotine or menthol-related changes in stimulant effects , nicotine withdrawal symptoms or ad-lib use . CONCLUSIONS Menthol , even at very low doses , alters the appeal of e-cigarettes among youth . Further , menthol enhances positive rewarding effects of high nicotine-containing e-cigarettes among youth |
12,434 | 26,712,901 | FN rates in the observational studies are significantly higher than suggested by RCTs . | BACKGROUND Guidelines recommend primary prophylaxis ( PP ) with granulocyte-colony-stimulating factors ( G-CSF ) for patients above a febrile neutropenia ( FN ) risk threshold of 20 % .
Practitioners often use FN rates of regimens based on data from r and omized , controlled trials ( RCTs ) , which are often comprised of highly selected patients .
Patients in the community setting may be at higher risk of FN . | Background Weekly docetaxel has occasionally been used in the neoadjuvant to downstage breast cancer to reduce toxicity and possibly enhance quality of life . However , no studies have compared the st and ard three weekly regimen to the weekly regimen in terms of quality of life . The primary aim of our study was to compare the effects on QoL of weekly versus 3-weekly sequential neoadjuvant docetaxel . Secondary aims were to determine the clinical and pathological responses , incidence of Breast Conserving Surgery ( BCS ) , Disease Free Survival ( DFS ) and Overall Survival ( OS ) . Methods Eighty-nine patients receiving four cycles of doxorubicin and cyclophosphamide were r and omised to receive twelve cycles of weekly docetaxel ( 33 mg/m2 ) or four cycles of 3-weekly docetaxel ( 100 mg/m2 ) . The Functional Assessment of Cancer Therapy-Breast and psychosocial question naires were completed . Results At a median follow-up of 71.5 months , there was no difference in the Trial Outcome Index scores between treatment groups . During weekly docetaxel , patients experienced less constipation , nail problems , neuropathy , tiredness , distress , depressed mood , and unhappiness . There were no differences in overall clinical response ( 93 % vs. 90 % ) , pathological complete response ( 20 % vs. 27 % ) , and breast-conserving surgery ( BCS ) rates ( 49 % vs. 42 % ) . Disease-free survival and overall survival were similar between treatment groups . Conclusions Weekly docetaxel is well-tolerated and has less distressing side-effects , without compromising therapeutic responses , Breast Conserving Surgery ( BCS ) or survival outcomes in the neoadjuvant setting .Trial registration IS RCT N : IS RCT PURPOSE Paclitaxel has significant antitumor activity in patients with metastaticbreast cancer who have been previously treated with or exposed to anthracycline-containing chemotherapy . In this prospect i ve r and omized trial , the role of paclitaxel was evaluated in an adjuvant setting to determine its impact on reducing the risk of recurrence in patients with operable breast cancer . EXPERIMENTAL DESIGN Five hundred twenty-four patients were r and omized to be treated either with 4 cycles of paclitaxel followed by 4 cycles of combination therapy with 5-fluorouracil , Adriamycin , and cyclophosphamide ( Pac/FAC ) or with 8 cycles of FAC alone . Patients with intact primary breast cancer received the initial 4 cycles of paclitaxel or 4 cycles of FAC in a neoadjuvant setting . Planned duration of therapy was the same in all patients . After completion of 8 cycles of chemotherapy , those patients who were > or = 50 years and whose tumors were positive for estrogen receptors received tamoxifen for 5 years . RESULTS Ninety-two patients have had a recurrence after a median follow-up of 60 months with a range of 5 - 89 months . Estimated disease-free survival at 48 months was 0.83 for FAC and 0.86 for Pac/FAC group . The difference between the two groups was not statistically significant ( P = 0.09 ) . The overall estimated hazard ratio for Pac/FAC compared with FAC derived by fitting the Cox regression model and incorporating terms for prognostic factors was 0.66 . CONCLUSION Preliminary results suggest that the addition of paclitaxel to a FAC regimen of adjuvant or neoadjuvant therapy may further reduce the risk of disease recurrence ; however , differences were not statistically significant . At the time of this analysis , there have been 47 deaths . The survival data are too preliminary to permit meaningful evaluation of the impact of paclitaxel on mortality BACKGROUND The aim of the study was to analyse the toxicity and health related quality of life ( HRQoL ) of breast cancer patients treated with FAC ( 5-fluorouracil , doxorubicin , cyclophosphamide ) and TAC ( docetaxel , doxorubicin , cyclophosphamide ) with and without primary prophylactic G-CSF ( PPG ) . PATIENTS AND METHODS This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients . After the entry of the first 237 patients , the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia . A total of 1047 evaluable patients from 49 centres in Spain , two in Pol and and four in Germany were included in the trial . Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 question naires were compared in the three groups ( FAC , TAC pre-amendment and TAC post-amendment ) . RESULTS The addition of PPG to TAC significantly reduced the incidence of neutropenic fever , grade 2 - 4 anaemia , asthenia , anorexia , nail disorders , stomatitis , myalgia and dysgeusia . Patient QoL decreased during chemotherapy , more with TAC than FAC , but returned to baseline values afterwards . The addition of PPG to TAC significantly reduced the percentage of patients with clinical ly relevant Global Health Status deterioration ( 10 or more points over baseline value ) at the end of chemotherapy ( 64 % versus 46 % , P<0.03 ) . CONCLUSIONS The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects . The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG , particularly in the final part of chemotherapy treatment OBJECTIVE The 7-year follow-up of the US oncology 9735 trial demonstrated the superiority of TC [ docetaxel (DTX)/cyclophosphamide ( CPA ) ] to doxorubicin/CPA therapy . To introduce TC therapy in Japan , the verification of the safety and tolerability is essential . We performed a collaborative prospect i ve safety study with Okayama University to introduce TC therapy . METHODS The subjects were 53 patients aged from 33 to 67 years at intermediate risk based on the St Gallen risk classification who underwent radical surgery for primary breast cancer between August 2007 and December 2008 . As post-operative adjuvant chemotherapy , four cycles of TC ( DTX 75 mg/m(2 ) + CPA 600 mg/m(2 ) ) were administered at 3-week intervals . Adverse events were evaluated based on National Cancer Institute-Common Terminology Criteria for Adverse Events ver . 3.0 . The safety and completion rate were evaluated as the primary and secondary endpoints , respectively . RESULTS Regarding hematological toxicity , Grade ( G ) 4 neutropenia occurred in 71.7 % and G3 in 26.4 % . G3 - 4 leukopenia developed in 32.1 % and 56.6 % , respectively , G4 anemia in 1.9 % and G1 - 2 anemia in 26.4 % . Regarding non-hematological toxicity , systemic malaise , skin eruption , edema , myalgia , arthralgia and nausea were noted in most patients . The completion rate was 94.3 % , dose reduction was necessary in 7.5 % and granulocyte colony-stimulating factor ( G-CSF ) support was required in 17.0 % . On comparison between patients aged 65 years or older and younger than 65 years , the completion rate , dose reduction and incidence of febrile neutropenia ( FN ) were higher in the elderly patients . G-CSF support was more often needed in this subgroup . CONCLUSIONS TC therapy is tolerable for Japanese patients , but attention should be paid to the development of FN and neutropenia . The completion rate was lower in the elderly patients , showing that tolerability was not necessarily favorable PURPOSE We previously reported that four cycles of docetaxel/cyclophosphamide ( TC ) produced superior disease-free survival ( DFS ) compared with four cycles of doxorubicin/cyclophosphamide ( AC ) in early breast cancer . Older women are under-represented in adjuvant chemotherapy trials . In our trial 16 % of patients were > or = 65 years . We now report 7-year results for DFS and overall survival ( OS ) as well as the impact of age , hormone receptor status , and HER2 status on outcome and toxicity . PATIENTS AND METHODS Patients were r and omly assigned to receive either four cycles of st and ard-dose AC ( 60/600 mg/m(2 ) ; n = 510 ) , or TC ( 75/600 mg/m(2 ) ; n = 506 ) , administered by intravenous infusion every 3 weeks . RESULTS The median age in women younger than 65 , was 50 years ( range , 27 to 64 ) and for women > or = 65 was 69 years ( range , 65 to 77 ) . Baseline characteristics in the two age subgroups were generally well matched , except that older women tended to have more lymph node involvement . At a median of 7 years follow-up , the difference in DFS between TC and AC was significant ( 81 % TC v 75 % AC ; P = .033 ; hazard ratio [ HR ] , 0.74 ; 95 % CI 0.56 to 0.98 ) as was OS ( 87 % TC v 82 % AC ; P = .032 ; HR , 0.69 ; 95 % CI , 0.50 to 0.97 ) . TC was superior in older patients as well as younger patients . There was no interaction of hormone-receptor status or HER-2 status and treatment . Older women experienced more febrile neutropenia with TC and more anemia with AC . CONCLUSION With longer follow-up , four cycles of TC was superior to st and ard AC ( DFS and OS ) and was a tolerable regimen in both older and younger patients PURPOSE To determine the influence of the epirubicin dose in operable node-positive breast cancer patients with factors of poor prognosis . PATIENTS AND METHODS Between April 1990 and July 1993 , 565 operable breast cancer patients with either more than three positive nodes or between one and three positive nodes with Scarff Bloom Richardson grade > or = 2 and hormone receptor negativity were r and omized after surgery to receive either fluorouracil 500 mg/m(2 ) , epirubicin 50 mg/m(2 ) , and cyclophosphamide 500 mg/m(2 ) every 21 days for six cycles ( FEC 50 ) or the same regimen except with epirubicin dose of 100 mg/m(2 ) ( FEC 100 ) . Postmenopausal patients received tamoxifen 30 mg/d for 3 years at the beginning of chemotherapy . Radiotherapy was delivered at the end of chemotherapy in both groups . RESULTS The median follow-up was 67 months . The 5-year disease-free survival ( DFS ) was 54.8 % with FEC 50 and 66.3 % with FEC 100 ( P = .03 ) . The 5-year overall survival ( OS ) was 65.3 % and 77.4 % , respectively ( P = .007 ) . The mean relative dose-intensity was similar in the two groups ( 90.3 % and 86.1 % , respectively ) . Neutropenia and anemia were significantly more frequent in FEC 100 ( P < 10(-3 ) ) , as were nausea-vomiting ( P = .008 ) and stomatitis and alopecia ( P < 10(-3 ) ) . Nine cases of grade 3 infection occurred only with FEC 100 , and no toxic deaths occurred . Three cases of acute cardiac toxicity were observed ( FEC50 = 1 , FEC100 = 2 ) and 10 patients ( FEC50 = 6 , FEC100 = 4 ) presented delayed cardiac dysfunctions . Two cases of secondary leukemia were observed ( acute lymphatic leukemia with FEC 50 and acute myelogenous leukemia with FEC 100 ) . CONCLUSION After 5 years of follow-up , the increased epirubicin dose led to a significant benefit in terms of DFS and OS , with a high survival rate among patients with poor-prognosis breast cancer BACKGROUND Chemotherapy-induced neutropenia is the most common adverse effect of chemotherapy and is often complicated by febrile neutropenia ( FN ) . The objective of this study is to vali date a classification of aggressiveness of a chemotherapy regimen and to evaluate its usefulness in a risk prediction model of FN in patients with hematological cancer at the beginning of a chemotherapy cycle . PATIENTS AND METHODS Two hundred and sixty-six patients were prospect ively enrolled and followed during 1053 cycles . Relevant patient informations were collected at the beginning of the first cycle and the number of days of FN were counted in the follow-up [ dichotomized ( no FN versus > or= 1 day of FN ) ] . RESULTS Aggressive chemotherapy regimen is the major predictor of FN [ odds ratio 5.2 ( 3.2 - 8.4 ) ] . The other independent predictors are the underlying disease , an involvement of bone marrow , body surface < or= 2 m(2 ) , a baseline monocyte count < 150/microl and the interaction between the first cycle in the same treatment line and a baseline hemoglobin dosage . A rule of prediction of FN was computed with these characteristics : sensitivity 78.6 % , specificity 62.3 % , positive predictive value 42.7 % and negative predictive value 89.1 % . CONCLUSION Further studies are needed to vali date this score Summary Background Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment . The UK TACT study ( CRUK01/001 ) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with st and ard chemotherapy of similar duration . Methods In this multicentre , open-label , phase III , r and omised controlled trial , 4162 women ( aged > 18 years ) with node-positive or high-risk node-negative operable early breast cancer were r and omly assigned by computer-generated permuted block r and omisation to receive FEC ( fluorouracil 600 mg/m2 , epirubicin 60 mg/m2 , cyclophosphamide 600 mg/m2 at 3-weekly intervals ) for four cycles followed by docetaxel ( 100 mg/m2 at 3-weekly intervals ) for four cycles ( n=2073 ) or control ( n=2089 ) . For the control regimen , centres chose either FEC for eight cycles ( n=1265 ) or epirubicin ( 100 mg/m2 at 3-weekly intervals ) for four cycles followed by CMF ( cyclophosphamide 600 mg/m2 , methotrexate 40 mg/m2 , and fluorouracil 600 mg/m2 at 4-weekly intervals ) for four cycles ( n=824 ) . The primary endpoint was disease-free survival . Analysis was by intention to treat ( ITT ) . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N79718493 . Findings All r and omised patients were included in the ITT population . With a median follow-up of 62 months , disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls ( hazard ratio [ HR ] 0·95 , 95 % CI 0·85–1·08 ; p=0·44 ) . 75·6 % ( 95 % CI 73·7–77·5 ) of patients in the experimental group and 74·3 % ( 72·3–76·2 ) of controls were alive and disease-free at 5 years . The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group ( p<0·0001 ) ; the most frequent events were neutropenia ( 937 events vs 797 events ) , leucopenia ( 507 vs 362 ) , and lethargy ( 456 vs 272 ) . Interpretation This study did not show any overall gain from the addition of docetaxel to st and ard anthracycline chemotherapy . Exploration of predictive biomarker-defined subgroups might have the potential to better target the use of taxane-based therapy . Funding Cancer Research UK ( CRUK 01/001 ) , Sanofi-Aventis , Pfizer , and Roche BACKGROUND This study was design ed to determine whether delivering neo-adjuvant chemotherapy at a higher dose in a shorter period of time improves outcome of breast cancer patients . PATIENTS AND METHODS Women with newly diagnosed breast cancer were r and omly assigned to neoadjuvant chemotherapy of four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel ( AC 60/600 - T 100 mg/m(2 ) ) or six cycles of TAC ( 75/50/500 mg/m(2 ) ) every 3 weeks . The primary endpoint was the pathologic complete response ( pCR ) rate , defined as no invasive tumour present in the breast . RESULTS In total , 201 patients were included . Baseline characteristics were well balanced . AC-T result ed in pCR in 21 % and TAC in 16 % of patients ( odds ratio 1.44 ( 95 % confidence interval ( CI ) 0.67 - 3.10 ) . AC-T without primary granulocyte-colony stimulating factor ( G-CSF ) prophylaxis was associated with more febrile neutropenia compared to TAC with primary G-CSF prophylaxis ( 23 % versus 9 % ) , and with more grade 3/4 sensory neuropathy ( 5 % versus 0 % ) . CONCLUSIONS With a higher cumulative dose for the concurrent arm , no differences were observed between the two treatment arms with respect to pCR rate . The differential toxicity profile could partly be explained by different use of primary G-CSF prophylaxis PURPOSE Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer ( BC ) . Currently , however , most patients with BC are node negative at diagnosis . The only pure node-negative study ( Spanish Breast Cancer Research Group 9805 ) reported so far showed a docetaxel benefit but significant toxicity . Here we tested the efficacy and safety of weekly paclitaxel ( wP ) in node-negative patients , which is yet to be established . PATIENTS AND METHODS Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence ( according to St. Gallen 1998 criteria ) were eligible . After primary surgery , 1,925 patients were r and omly assigned to receive fluorouracil , doxorubicin , and cyclophosphamide ( FAC ) × 6 or FAC × 4 followed by wP × 8 ( FAC-wP ) . The primary end point was disease-free survival ( DFS ) after a median follow-up of 5 years . Secondary end points included toxicity and overall survival . RESULTS After a median follow-up of 63.3 months , 93 % and 90.3 % of patients receiving FAC-wP or FAC regimens , respectively , remained disease free ( hazard ratio [ HR ] , 0.73 ; 95 % CI , 0.54 to 0.99 ; log-rank P = .04 ) . Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died ( one and seven from cardiovascular diseases , respectively ; HR , 0.79 ; 95 % CI , 0.49 to 1.26 ; log-rank P = .31 ) . The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia ( 2.7 % v 3.6 % ) , fatigue ( 7.9 % v 3.4 % ) , and sensory neuropathy ( 5.5 % v 0 % ) . CONCLUSION For patients with high-risk node-negative BC , the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy , in addition to manageable toxicity , especially regarding long-term cardiac effects A risk model for febrile neutropenia ( FN ) after conventional cytotoxic chemotherapy , based on early ( day 5 ) lymphopenia and the dose of chemotherapy , has been described . A risk index based on parameters available at day 1 would be easier in daily practice . The objectives of this work were ( 1 ) to investigate a risk model for FN using only day 1 blood cell count and ( 2 ) to compare the day 1 and day 5 risk models . Three series of patients were used for the delineation and /or validation of these two risk models : ( 1 ) the exhaustive cohort of 950 patients treated in the Department of Medicine of the CLB in 1996 ( CLB-1996 series ) , ( 2 ) the Elypse 1 series , a prospect i ve series of 321 patients treated in community hospitals and regional cancer centres , and ( 3 ) a previously reported Elypse 0 series of 329 patients . Day 1 blood cell count was available in all three series , while day 5 blood cell count was available only in the Elypse 0 and 1 series . In the CLB-1996 series , 92 ( 9.7 % ) patients experienced FN ; only chemotherapy dose and day 1 lymphopenia ⩽700 μl−1 had an independent prognostic value for FN in multivariate analysis . In patients with both risk factors ( ‘ high-risk group ’ ) , the incidence of FN was 44 , 50 and 61 % in the CLB-1996 . Elypse 1 and 0 series , respectively , indicating that the ‘ day 1 ’ risk model enables one to identify patients at high-risk for FN . Besides , the observed incidence of FN in the high-risk group of the ‘ day 5 ’ model ( i.e. patients with day 5 lymphopenia ⩽700 μl−1 and receiving high-risk CT ) was 45 and 69 % in the Elypse 0 and 1 series , respectively . In the Elypse 1 and 0 series , 15 and 12 % of all patients who experienced FN were in the high-risk group of the ‘ day 1 ’ risk model as compared to 25 and 62 % for the high-risk group of the ‘ day 5 ’ risk model . Both day 1 and day 5 lymphopenia are associated with an increased risk of FN in patients treated with chemotherapy . The ‘ day 1 ’ model identifies a small population of patients at high risk for FN , but has a lower sensitivity than the day 5 model PURPOSE We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients . PATIENTS AND METHODS Patients were r and omly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m(2 ) docetaxel . The primary end point was the percentage of patients developing febrile neutropenia ( defined as body temperature > /= 38.2 degrees C and neutrophil count < 0.5 x 10(9)/L on the same day of the fever or the day after ) . Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia , intravenous ( IV ) anti-infectives required for febrile neutropenia , and the ability to maintain planned chemotherapy dose on time . Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles . RESULTS Nine hundred twenty-eight patients received placebo ( n = 465 ) or pegfilgrastim ( n = 463 ) . Patients receiving pegfilgrastim , compared with patients receiving placebo , had a lower incidence of febrile neutropenia ( 1 % v 17 % , respectively ; P < .001 ) , febrile neutropenia-related hospitalization ( 1 % v 14 % , respectively ; P < .001 ) , and use of IV anti-infectives ( 2 % v 10 % , respectively ; P < .001 ) . The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo ( 80 % and 78 % , respectively ) , as would be expected of the study design . Pegfilgrastim was generally well tolerated and safe , and the adverse events reported were typical of this patient population . CONCLUSION First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia , febrile neutropenia-related hospitalizations , and IV anti-infective use Introduction Based on the variable benefit of taxanes in the adjuvant setting of early breast cancer in certain tumor phenotypes , especially in human epidermal growth factor receptor (HER)2-positive and triple-negative disease , and with the observation of a lesser benefit in luminal A , this research article aim ed at exploring the value of docetaxel in patients with an estrogen receptor-positive , HER2-negative disease phenotype , who might not derive the same benefits as those with other phenotypes . Patients and methods This was a r and omized prospect i ve study comparing disease-free survival ( DFS ) and safety profile of sequential adjuvant three cycles Fluorouracil , Epirubicin , Cyclophosphamide followed by three cycles Docetaxel ( FEC-D ) versus six cycles classic Fluorouracil , Epirubicin , Cyclophosphamide (FEC)-100 in 60 Egyptian women who presented to Dar Al Fouad Hospital during the period June 2007 to July 2008 with ( pT1 - 2 pN0 - 3 M0 ) . The primary end point was DFS in a follow-up period of 4 years . The secondary end point was toxicity profile . Results Four-year DFS rates were comparable in both arms : 73.3 % ± 8.1 % in the FEC-D arm versus 76.5 % ± 7.8 % in the FEC-100 arm ( P = 0.83 ) . N3 and grade III subgroups achieved the worst DFS in both subgroups ( P = 0.001 and P = 0.214 , respectively ) . The rate of nausea and vomiting was higher in the FEC-100 arm ( P = 0.49 ) , while grade III – IV neutropenia and febrile neutropenia incidence was similar between both arms . Conclusion Sequential adjuvant chemotherapy with FEC followed by docetaxel achieved comparable DFS results to FEC alone in luminal A phenotype subgroups of breast cancer Up date d international guidelines published in 2006 have broadened the scope for the use of granulocyte colony-stimulating factor ( G-CSF ) in supporting delivery of myelosuppressive chemotherapy . G-CSF prophylaxis is now recommended when the overall risk of febrile neutropenia ( FN ) due to regimen and individual patient factors is ≥20 % , for supporting dose-dense and dose-intense chemotherapy and to help maintain dose density where dose reductions have been shown to compromise outcomes . Indeed , there is now a large body of evidence for the efficacy of G-CSFs in supporting dose-dense chemotherapy . Predictive tools that can help target those patients who are most at risk of FN are now becoming available . Recent analyses have shown that , by reducing the risk of FN and chemotherapy dose delays and reductions , G-CSF prophylaxis can potentially enhance survival benefits in patients receiving chemotherapy in curative setting s. Accumulating data from ‘ real-world ’ clinical practice setting s indicate that patients often receive abbreviated courses of daily G-CSF and consequently obtain a reduced level of FN protection . A single dose of PEGylated G-CSF ( pegfilgrastim ) may provide a more effective , as well as a more convenient , alternative to daily G-CSF . Prospect i ve studies are needed to vali date the importance of delivering the full dose intensity of st and ard chemotherapy regimens , with G-CSF support where appropriate , across a range of setting s. These studies should also incorporate prospect i ve evaluation of risk stratification for neutropenia and its complications PURPOSE To determine the relative efficacy of an intensive cyclophosphamide , epirubicin , and fluorouracil ( CEF ) adjuvant chemotherapy regimen compared with cyclophosphamide , methotrexate , and fluorouracil ( CMF ) in node-positive breast cancer . PATIENTS AND METHODS Premenopausal women with node-positive breast cancer were r and omly allocated to receive either cyclophosphamide 100 mg/m2 orally days 1 through 14 ; methotrexate 40 mg/m2 intravenously ( i.v . ) days 1 and 8 ; and fluorouracil 600 mg/m2 i.v . days 1 and 8 or cyclophosphomide 75 mg/m2 orally days 1 through 14 ; epirubicin 60 mg/m2 i.v . days 1 and 8 ; and fluorouracil 500 mg/m2 i.v . days 1 and 8 . Each cycle was administered monthly for 6 months . Patients administered CEF received antibiotic prophylaxis with cotrimoxazole two tablets twice a day for the duration of chemotherapy . RESULTS The median follow-up was 59 months . One hundred sixty-nine of the 359 CMF patients developed recurrence compared with 132 of the 351 CEF patients . The corresponding 5-year relapse-free survival rates were 53 % and 63 % , respectively ( P = .009 ) . One hundred seven CMF patients died compared with 85 CEF patients . The corresponding 5-year actuarial survival rates were 70 % and 77 % , respectively ( P = .03 ) . The rate of hospitalization for febrile neutropenia was 1.1 % in the CMF group compared with 8.5 % in the CEF group . There was one case of congestive heart failure in a patient who received CMF compared with none in the CEF group . Acute leukemia occurred in five patients in the CEF group . CONCLUSION The results of this trial show the superiority of CEF over CMF in terms of both disease-free and overall survival in premenopausal women with axillary node-positive breast cancer Trastuzumab is considered effective against human epidermal growth factor receptor (HER)-2-positive breast cancer as assessed by immunohistochemistry ( IHC ) and fluorescence or chromogenic in situ hybridization ( FISH/CISH ) on biopsy material . Trastuzumab is now approved in both the adjuvant and metastatic setting s for this patient population . Because HER-2 extracellular domain ( ECD ) levels have been correlated with disease progression in the metastatic setting , we considered trastuzumab salvage therapy plus a taxane in heavily pretreated trastuzumab-naive relapsed breast cancer patients with high serum levels of HER-2 ECD ( > or = 15 ng/ml ) . All patients had previously failed at least two lines of anthracycline- and taxane-based regimens and were HER-2 negative by IHC and FISH/CISH prior to a central ized re analysis , and were serum positive for HER-2 ECD ( > or = 15 ng/ml ) at baseline . Regular serum accounts of HER-2 ECD were recorded and compared with response and survival outcomes . Twenty-two patients were finally eligible for salvage therapy . Minor responses were observed in five ( 23 % ) and stable disease ( SD ) was observed in 11 patients , leading to a clinical benefit rate of 73 % ( 16 of 22 patients ) . The median time to progression and overall survival time were 5 ( 6.5 months in minor responders and SD ) and 12 months , respectively ; 11 and eight patients remained progression free for > 6 and > 12 months , respectively . Eleven and seven patients were alive at 12 and 15 months , respectively , after treatment start . Furthermore , in total , 13 ( 59.1 % ) patients obtained a biochemical response . In our study , patients with conventionally HER-2-negative disease but with expression of HER-2 ECD above the normal limit ( > or = 15 ng/ml ) displayed a rapid response , both biochemically and clinical ly , to the trastuzumab-taxane combination . This is the first study assessing anti-HER-2-based treatment in HER-2-negative advanced breast cancer according to HER-2 ECD positivity ; if our results are confirmed , additional patients with " hidden " HER-2-positive breast cancer might benefit from anti-HER-2 treatment Background Few data are available on compliance and safety of adjuvant chemotherapy when indicated in elderly breast cancer patients ; CMF ( cyclophosphamide , methotrexate , fluorouracil ) can be reasonably considered the most widely accepted st and ard of treatment . Methods We retrospectively review ed compliance and safety of adjuvant CMF in patients older than 60 . The treatment was indicated if patients had no severe comorbidity , a high-risk of recurrence , and were younger than 75 . Toxicity was coded by NCI-CTC . Toxicity and compliance were compared between two age subgroups ( < 65 , ≥ 65 ) by Fisher exact test and exact Wilcoxon rank-sum test . Results From March 1991 to March 2002 , 180 patients were identified , 100 older than 60 and younger than 65 , and 80 aged 65 or older . Febrile neutropenia was more frequent among older patients ( p = 0.05 ) . Leukopenia , neutropenia , nausea , cardiac toxicity and thrombophlebitis tended to be more frequent or severe among elderlies , while mucositis tended to be more evident among younger patients , all not significantly . Almost one half ( 47 % ) of the older patients receiving concomitant radiotherapy experienced grade 3–4 haematological toxicity . Compliance was similar in the two groups , with 6 cycles administered in 86 % and 79 % , day-8 chemotherapy omitted at least once in 36 % and 39 % , dose reduction in 27 % and 38 % , prolonged treatment duration ( ≥ 29 weeks ) in 10 % and 11 % and need of G-CSF in 9 % and 18 % , among younger and older patients , respectively . Conclusion Our data show that , in a highly selected population of patients 65 or more years old , CMF is as feasible as in patients older than 60 and younger than 65 , but with a relevant burden of toxicity . We suggest that prospect i ve trials in elderly patients testing less toxic treatment schemes are m and atory before indicating adjuvant chemotherapy to all elderly patients with significant risk of breast cancer recurrence This r and omized , double-blind , phase III trial compared granulocyte colony-stimulating factor ( G-CSF ; filgrastim ) and leridistim ( formerly myelopoietin ) , a chimeric dual agonist that binds both G-CSF and interleukin-3 receptors , for the prevention of neutropenic complications in patients with breast cancer receiving TAC ( docetaxel/doxorubicin/cyclophosphamide ) chemotherapy . Patients with metastatic ( 44 % ) or localized breast cancer ( 56 % ) were r and omized to G-CSF 5 microg/kg subcutaneously ( s.c . ) daily ( n = 135 ) , leridistim 5 microg/kg s.c . daily ( n = 139 ) , or leridistim 10 microg/kg s.c . every other day alternating with placebo ( n = 139 ) . Following administration of TAC ( docetaxel 75 mg/m2 , doxorubicin 50 mg/m2 , cyclophosphamide 500 mg/m2 ) on day 1 , patients received growth factor beginning on day 2 until the postnadir absolute neutrophil count exceeded 1500 cells/ microL. Chemotherapy cycles were repeated every 21 days . The incidence of febrile neutropenia was 7 % in the G-CSF arm , 19 % in the daily leridistim arm ( P = 0.003 for comparison with G-CSF ) and 22 % in the alternate-day leridistim arm ( P < 0.001 for comparison with G-CSF ) . There was no significant difference between treatment arms in the cumulative percentage of patients experiencing grade 4 neutropenia at some point during therapy ( 85%-88 % ) . However , grade 4 neutropenia occurred in 53 % of cycles in the G-CSF cohort , 61 % of cycles in the daily leridistim group ( P = 0.063 for comparison with G-CSF ) , and 63 % of cycles in the alternate-day leridistim group ( P = 0.015 for comparison with G-CSF ) . We conclude that G-CSF is superior to leridistim in the prevention of febrile neutropenia in patients with advanced breast cancer receiving TAC chemotherapy . The up-front prophylactic use of G-CSF is a reasonable supportive therapy for patients treated with docetaxel/anthracycline-based combination chemotherapy PURPOSE We investigated whether capecitabine and docetaxel followed by fluorouracil , epirubicin , and cyclophosphamide ( FEC ) or weekly paclitaxel ( WP ) followed by FEC would improve relapse-free survival ( RFS ) in operable breast cancer . PATIENTS AND METHODS In this single-institution study , patients with clinical stages I to IIIC breast cancer were r and omly assigned on a 1:1 basis to WP 80 mg/m(2 ) for 12 weeks followed by fluorouracil 500 mg/m(2 ) , epirubicin 100 mg/m(2 ) , and cyclophosphamide 500 mg/m(2 ) ( FEC-100 ) every 3 weeks for four cycles or docetaxel 75 mg/m(2 ) on day 1 and capecitabine ( XT ) 1,500 mg/m(2 ) on days 1 through 14 every 3 weeks for four cycles followed by FEC for four cycles and stratified by timing of chemotherapy ( preoperative v adjuvant ) . Accrual was stopped short of 930 patients on the basis of a Bayesian predictive calculation that additional accrual would be unlikely to change the qualitative comparison of the two regimens . RESULTS After enrollment of 601 patients and a median follow-up of 50 months , we observed no improvement in RFS between XT ( 87.5 % ; 95 % CI , 82.7 % to 91.1 % ) and WP ( 90.7 % ; 95 % CI , 86.4 % to 93.7 % ; P = .51 ) . In the preoperative group , the pathologic complete response rate was 19.8 % and 16.4 % in the XT and WP arms , respectively ( P = .45 ) . Rates of breast-conserving surgery were similar between the two groups ( P = .48 ) . The XT arm had a significantly higher incidence of stomatitis ( P < .001 ) , h and -foot syndrome ( P < .001 ) , and neutropenic infection ( P < .001 ) . CONCLUSION There was no difference in efficacy between WP and XT as used in this r and omized phase III trial . XT was associated with higher GI , skin , and neutropenic-related toxicities The purpose of this study was to develop a model for predicting the occurrence of life-threatening neutropenia ( LN , ANC ≤ 0.5 × 109/1 ) and febrile neutropenia ( FN , an ANC ≤ 0.5 × l09/l in association with a body temperature of ≥ 38.3 ° C ) after the first cycle of CHOP therapy in patients newly diagnosed with aggressive NHL . One hundred and forty-five patients , aged ≥ 15 years , with newly diagnosed diffuse mixed , diffuse large-cell or large-cell immunoblastic lymphoma ( IWF categories , F , G , H ) , who had been treated with CHOP at King Chulalongkorn Memorial Hospital between June 1994 and December 1998 , were entered into the study . The criteria for eligibilty included complete work-up for baseline evaluation , treatment with st and ard CHOP chemotherapy , at least one complete blood count performed during days 8 - 14 post-treatment or if at any time the patients experienced a BT of ≥ 38.3 ° C and were not treated with any colony-stimulating factors ( CSFs ) . The median age of the patients was 47 years ( range , 17 - 78 ) . Forty-eight percent of the patients were in stage III/IV , 36 % had ECOG performance status ( PS ) II-IV , 30 % had ≥ 2 extranodal diseases , 59 % had serum LDH > 1 × normal and 23 % had bone marrow involvement . The frequencies of patients in the low- , low-intermediate , high-intermediate and high risk groups according to the international index were 29 % , 28 % , 17 % and 26 % , respectively . Thirty-nine percent of the patients had LN at nadir and 33 % developed FN after the first course of CHOP . By using stepwise logistic regression analysis , the pretreatment variables independently predictive of the LN at nadir and the FN were serum albumin concentration of ≤ 3.5 g/dl , serum LDH > 1 × normal and whether there was bone marrow involvement of lymphoma at presentation . The model , based on the incorporation of these three factors , identified three risk groups of patients with a predicted probability of developing LN at nadir of 81.5 % ( 95 % CI , 68.5 - 90.7)(high risk ) , 23.9 % ( 95 % CI , 12.6 - 38.8)(intermediate risk ) and 4.4 % ( 95 % CI , 0.5- 15.1)(low risk ) . The predicted rate of FN in the three groups were 72.2 % ( 95 % CI , 58.4 - 83.5 ) , 17.4 % ( 95 % CI , 7.8 - 31.4 ) and 2.2 % ( 95 % CI , 0.05 - 11.8 ) , respectively . In conclusion , our model could be used as a means to identify patients with newly diagnosed aggressive NHL , treated with CHOP , who are at high risk ( ≥ 50 % probability ) of developing post-first course LN and FN , in whom CSF and /or antibiotic prophylaxis might be indicated BACKGROUND To determine whether a dose-dense regimen improves outcome in early breast cancer patients , we compared outcomes with the same fluorouracil , epirubicin , and cyclophosphamide ( FEC ) chemotherapeutic regimen administered every 3 weeks ( FEC21 ) or administered every 2 weeks ( FEC14 including support with filgrastim , a granulocyte colony-stimulating factor ) in a multicenter phase III r and omized trial . METHODS A total of 1214 patients with early-stage breast cancer were r and omly assigned to receive six cycles of FEC14 ( 604 patients ) or of FEC21 ( 610 patients ) . Study endpoints were overall survival and event-free survival . Associations were assessed by multivariable analysis with adjustment for age ; tumor size ; grade ; proliferative rate ; and menopausal , lymph node , estrogen receptor , and progesterone receptor status . All statistical tests were two-sided . RESULTS Patients in the FEC14 arm had fewer dose reductions or treatment delays or discontinuation ( 26 % ) than those in the FEC21 arm ( 33 % ) ( difference = 7 % , 95 % confidence interval [ CI ] = 2 % to 12 % ; P = .008 ) . FEC14 therapy , compared with FEC21 therapy , was associated with more asthenia ( 36 % versus 29 % , difference = 7 % , 95 % CI = 2 % to 12 % ; P = .01 ) , bone pain ( 33 % versus 4 % , difference = 29 % , 95 % CI = 25 % to 33 % ; P < .001 ) , anemia ( 38 % versus 19 % , difference = 19 % , 95 % CI = 14 % to 24 % ; P < .001 ) , and thrombocytopenia ( 8 % versus 2 % , difference = 6 % , 95 % CI = 4 % to 9 % ; P < .001 ) , but with less leukopenia ( 12 % versus 45 % , difference = 33 % , 95 % CI = 28 % to 37 % ; P < .001 ) . No acute myelogenous leukemia or myelodysplastic syndrome was observed . At a median follow-up of 10.4 years , no statistically significant difference in the hazard of death ( hazard ratio [ HR ] = 0.87 , 95 % CI = 0.67 to 1.13 ) or recurrence ( HR = 0.88 , 95 % CI = 0.71 to 1.08 ) was found between FEC14 and FEC21 groups after adjustment by multivariable analysis . Although the study was underpowered for subset analysis , we found no evidence that the effect of the treatment type was associated with any of the potential prognostic factors . CONCLUSION Our results support the long-term safety of FEC14 chemotherapy as an adjuvant treatment of breast cancer . However , this therapy was not associated with improved outcome , but because of the limited statistical power of our study , we can not rule out a modest improvement in outcome associated with FEC14 therapy Within an ongoing multicentre phase 3 r and omised trial ( ELDA , cancertrials.gov ID : NCT00331097 ) , early breast cancer patients , 65 - 79 years old , with average to high risk of recurrence , are r and omly assigned to receive CMF ( cyclophosphamide 600 mg/m2 , methotrexate 40 mg/m2 , fluorouracil 600 mg/m2 , days 1 - 8 ) or docetaxel ( 35 mg/m2 days 1 - 8 - 15 ) , every 4 weeks . Here we report an unplanned safety analysis prompted by an amendment introducing creatinine clearance as a tool to adjust methotrexate dose . Before such change , 101 patients with a median age of 70 were r and omly assigned CMF ( 53 patients ) or docetaxel ( 48 patients ) . At least one grade s 3 - 4 toxic event of any type was reported in 40 ( 75.5 % ) and 19 ( 39.6 % ) patients with CMF and docetaxel , respectively ( p=0.0002 ) . Grade s 3 - 4 hematological events were observed in 37 ( 69.8 % ) vs. 4 ( 8.3 % ) cases ( p<0.0001 ) and grade s 3 - 4 non-hematological toxicity in 12 ( 22.6 % ) vs. 15 ( 31.2 % ) patients ( p=0.11 ) , with CMF and docetaxel , respectively . A higher incidence of anemia , neutropenia , thrombocytopenia and febrile neutropenia was reported with CMF . Constipation , mucositis , nausea and vomiting were more common with CMF ; diarrhoea , abdominal pain , dysgeusia , neuropathy and liver toxicity were more frequent with docetaxel . No significant interaction was found between the occurrence of severe toxicity and baseline variables , including creatinine clearance and geriatric activity scales . In conclusion , weekly docetaxel appears to be less toxic than CMF in terms of hematological toxicity PURPOSE Using a 2 x 2 factorial design , we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin ( A ) , paclitaxel ( T ) , and cyclophosphamide ( C ) with concurrent doxorubicin and cyclophosphamide ( AC ) followed by paclitaxel ( T ) for disease-free ( DFS ) and overall survival ( OS ) ; to determine whether the dose density of the agents improves DFS and OS ; and to compare toxicities . PATIENTS AND METHODS A total of 2,005 female patients were r and omly assigned to receive one of the following regimens : ( I ) sequential A x 4 ( doses ) -- > T x 4 -- > C x 4 with doses every 3 weeks , ( II ) sequential A x 4 -- > T x 4 -- > C x 4 every 2 weeks with filgrastim , ( III ) concurrent AC x 4 -- > T x 4 every 3 weeks , or ( IV ) concurrent AC x 4 -- > T x 4 every 2 weeks with filgrastim . RESULTS A protocol -specified analysis was performed at a median follow-up of 36 months : 315 patients had experienced relapse or died , compared with 515 expected treatment failures . Dose-dense treatment improved the primary end point , DFS ( risk ratio [ RR ] = 0.74 ; P = .010 ) , and OS ( RR = 0.69 ; P = .013 ) . Four-year DFS was 82 % for the dose-dense regimens and 75 % for the others . There was no difference in either DFS or OS between the concurrent and sequential schedules . There was no interaction between density and sequence . Severe neutropenia was less frequent in patients who received the dose-dense regimens . CONCLUSION Dose density improves clinical outcomes significantly , despite the lower than expected number of events at this time . Sequential chemotherapy is as effective as concurrent chemotherapy Our objective was to determine whether oral etoposide and cisplatin combination ( EoP ) is superior to paclitaxel in the treatment of advanced breast cancer ( ABC ) patients pretreated with anthracyclines . From December 1997 to August 2003 , 201 patients were r and omised , 100 to EoP and 101 to paclitaxel arms . Four patients in each arm were ineligible . The doses of etoposide and cisplatin were 50 mg p.o . twice a day for 7 days and 70 mg m−2 intravenously ( i.v . ) on day 1 , respectively , and it was 175 mg m−2 on day 1 for paclitaxel . Both treatments were repeated every 3 weeks . A median of four cycles of study treatment was given in both arms . The response rate obtained in the EoP arm was significantly higher ( 36.3 vs 22.2 % ; P=0.038 ) . Median response duration was longer for the EoP arm ( 7 vs 4 months ) ( P=0.132 ) . Also , time to progression was significantly in favour of the EoP arm ( 5.5 vs 3.9 months ; P=0.003 ) . Median overall survival was again significantly longer in the EoP arm ( 14 vs 9.5 months ; P=0.039 ) . Toxicity profile of both groups was similar . Two patients in each arm were lost due to febrile neutropenia . The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines Abstract This r and omized , multicenter study compared the efficacy of docetaxel with or without capecitabine following fluorouracil/epirubicin/cyclophosphamide ( FEC ) therapy in operable breast cancer and investigated the role of Ki67 as a predictive biomarker . Patients were r and omized to 4 cycles of docetaxel/capecitabine ( docetaxel : 75 mg/m2 on day 1 ; capecitabine : 1,650 mg/m2 on days 1–14 every 3 weeks ) or docetaxel alone ( 75 mg/m2 on day 1 every 3 weeks ) after completion of 4 cycles of FEC ( 5-fluorouracil 500 mg/m2 , epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 every 3 weeks ) . The primary endpoint was the pathological complete response ( pCR ) rate . Predictive factor analysis was conducted using clinicopathological markers , including hormone receptors and Ki67 labeling index ( Ki67LI ) . A total of 477 patients were r and omized ; the overall response in the docetaxel/capecitabine and docetaxel groups was 88.3 and 87.4 % , respectively . There were no significant differences in the pCR rate ( docetaxel/capecitabine : 23 % ; docetaxel : 24 % ; p = 0.748 ) , disease-free survival , or overall survival . However , patients with mid-range Ki67LI ( 10–20 % ) showed a trend towards improved pCR rate with docetaxel/capecitabine compared to docetaxel alone . Furthermore , multivariate logistic regression analysis showed pre-treatment Ki67LI ( odds ratio 1.031 ; 95 % CI 1.014–1.048 ; p = 0.0004 ) to be a significant predictor of pCR in this neoadjuvant treatment setting . Docetaxel/capecitabine ( after 4 cycles of FEC ) did not generate significant improvement in pCR compared to docetaxel alone . However , exploratory analyses suggested that assessment of pre-treatment Ki67LI may be a useful tool in the identification of responders to preoperative docetaxel/capecitabine in early-stage breast cancer BACKGROUND Patients with an early response to neoadjuvant chemotherapy have chemosensitive tumors and a high probability for a pathological complete response at surgery . The relationship between extended chemotherapy and pathological complete response at surgery was investigated in a clinical trial . METHODS Untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/m(2 ) , doxorubicin at 50 mg/m(2 ) , and cyclophosphamide at 500 mg/m(2 ) ( TAC ) . Those whose tumor size decreased by 50 % or more by sonographic measurement ( ie , reduction in the product of the two largest perpendicular diameters by at least 50 % ) were classified as responders and r and omly assigned to receive four or six more cycles of TAC , for a total of six or eight TAC cycles . The primary aim was to increase the rate of a pathological complete response ( defined as no invasive or in situ residual tumor masses in the breast and lymph nodes ) from 20 % to 26 % . Sonographic response rates and rates of breast-conserving surgery and adverse effects were also assessed . All statistical tests were two-sided . RESULTS Of the 2090 patients in the GeparTrio trial , 1390 ( 66.5 % ) were r and omly assigned as responders after two initial TAC cycles to receive an additional four ( n = 704 ) or six ( n = 686 ) TAC cycles . Rates of pathological complete response were not statistically significantly different between the arms ( 21.0 % with six TAC cycles and 23.5 % with eight TAC cycles ; difference = 2.5 % , 95 % confidence interval [ CI ] = -1.8 % to 6.8 % ; P = .27 ) . More clinical ( 48.2 % vs 52.9 % , difference = 4.7 % ; 95 % CI = -0.55 % to 9.95 % ; P = .08 ) and sonographic ( 22.6 % vs 27.6 % , difference = 5 % ; 95 % CI = 0.45 % to 9.55 % ; P = .033 ) complete responses at surgery were observed with eight TAC cycles than with six TAC cycles . The rate of breast-conserving surgery was similar in both arms ( 67.5 % vs 68.5 % , respectively , P = .68 ) . Grade 3 or 4 leukopenia and edema and various grade 1 or 2 adverse events were more frequent in patients receiving eight TAC cycles than in those receiving six cycles . CONCLUSION Patients receiving eight TAC cycles had statistically significantly higher sonographic response rates but not pathological complete response rates than those receiving six TAC cycles . However , they also had more toxic effects . So far , eight cycles of TAC can not be recommended for the whole group of patients responding to two initial cycles of TAC Limited proven treatment options exist for patients with metastatic breast cancer ( MBC ) resistant to anthracycline and taxane treatment . Ixabepilone , a novel semisynthetic analog of epothilone B , has demonstrated single-agent activity in MBC resistant to anthracyclines and taxanes . In combination with capecitabine in a phase III trial ( CA163 - 046 ) in this setting , ixabepilone prolonged progression-free survival and increased objective response rate relative to capecitabine ( Thomas et al. J Clin Oncol 25:5210–5217 , 2007 ) . Here , we report the results of overall survival ( OS ) , a secondary efficacy endpoint from the CA163 - 046 trial . Seven hundred fifty-two patients with MBC resistant to anthracyclines and taxanes were r and omized to ixabepilone ( 40 mg/m2 intravenously on day 1 of a 21-day cycle ) plus capecitabine ( 2,000 mg/m2 orally on days 1 through 14 of a 21-day cycle ) or capecitabine alone ( 2,500 mg/m2 on the same schedule ) . Patients receiving ixabepilone plus capecitabine treatment had a median survival of 12.9 months compared to 11.1 months for patients receiving capecitabine alone ( HR = 0.9 ; 95%CI : 077–1.05 ; P = 0.19 ) . This observed increase in median OS favored the combination ; however , the difference was not statistically significant . Predefined subset analyses showed a clinical ly meaningful increase in OS in KPS 70–80 patients receiving ixabepilone plus capecitabine ( HR = 0.75 ; 95 % CI : 0.58–0.98 ) . Ixabepilone plus capecitabine did not show a significant improvement in survival compared to capecitabine alone in patients with MBC resistant to anthracyclines and taxanes . The observed differences in survival favored the combination arm . A clinical benefit was also seen in patients in the KPS 70–80 subgroup ( Clinical Trials.gov number , NCT000080301 ) PURPOSE Anthracycline- and taxane-based three-drug chemotherapy regimens have proven benefit as adjuvant therapy for early-stage breast cancer . This trial ( NSABP B-38 ; Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer ) asked whether the incorporation of a fourth drug could improve outcomes relative to two st and ard regimens and provided a direct comparison of those two regimens . PATIENTS AND METHODS We r and omly assigned 4,894 women with node-positive early-stage breast cancer to six cycles of docetaxel , doxorubicin , and cyclophosphamide ( TAC ) , four cycles of dose-dense ( DD ) doxorubicin and cyclophosphamide followed by four cycles of DD paclitaxel ( P ; DD AC→P ) , or DD AC→P with four cycles of gemcitabine ( G ) added to the DD paclitaxel ( DD AC→PG ) . Primary granulocyte colony-stimulating factor support was required ; erythropoiesis-stimulating agents ( ESAs ) were used at the investigator 's discretion . RESULTS There were no significant differences in 5-year disease-free survival ( DFS ) between DD AC→PG and DD AC→P ( 80.6 % v 82.2 % ; HR , 1.07 ; P = .41 ) , between DD AC→PG and TAC ( 80.6 % v 80.1 % ; HR , 0.93 ; P = .39 ) , in 5-year overall survival ( OS ) between DD AC→PG and DD AC→P ( 90.8 % v 89.1 % ; HR , 0.85 ; P = .13 ) , between DD AC→PG and TAC ( 90.8 % v 89.6 % ; HR , 0.86 ; P = .17 ) , or between DD AC→P versus TAC for DFS ( HR , 0.87 ; P = .07 ) and OS ( HR , 1.01 ; P = .96 ) . Grade 3 to 4 toxicities for TAC , DD AC→P , and DD AC→PG , respectively , were febrile neutropenia ( 9 % , 3 % , 3 % ; P < .001 ) , sensory neuropathy ( < 1 % , 7 % , 6 % ; P < .001 ) , and diarrhea ( 7 % , 2 % , 2 % ; P < .001 ) . Exploratory analyses for ESAs showed no association with DFS events ( HR , 1.02 ; P = .95 ) . CONCLUSION Adding G to DD AC→P did not improve outcomes . No significant differences in efficacy were identified between DD AC→P and TAC , although toxicity profiles differed Background The use of granulocyte colony-stimulating factor ( G-CSF ) as a prophylaxis against febrile neutropenia ( FN ) is well documented in the literature ; however , the therapeutic use of G-CSF in the treatment of FN remains controversial . This study assessed the efficacy of adjunctive G-CSF in the treatment of FN by evaluating clinical outcomes . Methods This was a single-center , prospect i ve cohort study conducted at the National Cancer Center in Singapore . Adult patients who had received chemotherapy and developed FN between January 2009 and January 2012 were included in the analysis . The clinical efficacy of adjunctive G-CSF was evaluated by investigating the duration of hospitalization , duration to absolute neutrophil count ( ANC ) recovery , duration of grade IV neutropenia , duration to fever resolution , duration of antibiotic therapy , and incidence of documented infections . A multivariate analysis was performed to identify patients who could potentially benefit from adjunctive G-CSF . Results Four hundred and thirty patients were analyzed . Majority manifested low-risk FN ( 81.2 % ) based on the Multinational Association of Supportive Care in Cancer ( MASCC ) scoring . Compared to patients who did not receive adjunctive G-CSF , patients receiving adjunctive G-CSF had a nonsignificant reduction in the duration of hospitalization ( 3.5 vs. 3.7 days , p = 0.41 ) and in ANC recovery time ( 3.4 vs. 3.5 days , p = 0.76 ) . Neutropenia-related mortality was lower among those who have received adjunctive G-CSF ( 2.4 vs. 8.4 % , p = 0.006 ) . Patients of Indian ethnicity and those who underwent gemcitabine-containing chemotherapy were less likely to receive adjunctive G-CSF treatment . Conclusions This observational study suggested that adjunctive G-CSF may confer clinical benefits among solid tumor and lymphoma patients with established febrile neutropenia . Further research should be conducted to vali date the findings PURPOSE Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy , but some patients are at low risk for serious medical complications . The purpose of this study was to develop an internationally vali date d scoring system to identify these patients . MATERIAL S AND METHODS Febrile neutropenic cancer patients were observed in a prospect i ve multinational study . Independent factors assessable at fever onset , predicting low risk of complications , on a r and omly selected derivation set , were assigned integer weights to develop a risk-index score , which was subsequently tested on a validation set . RESULTS On the derivation set ( 756 patients ) , predictive factors were a burden of illness indicating absence of symptoms or mild symptoms ( weight , 5 ; odds ratio [ OR ] , 8.21 ; 95 % confidence interval [ CI ] , 4.15 to 16.38 ) or moderate symptoms ( weight , 3 ; OR , 3.70 ; 95 % CI , 2.18 to 6.29 ) ; absence of hypotension ( weight , 5 ; OR , 7.62 ; 95 % CI , 2.91 to 19.89 ) ; absence of chronic obstructive pulmonary disease ( weight , 4 ; OR , 5 . 35 ; 95 % CI , 1.86 to 15.46 ) ; presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies ( weight , 4 ; OR , 5.07 ; 95 % CI , 1.97 to 12.95 ) ; outpatient status ( weight , 3 ; OR , 3.51 ; 95 % CI , 2.02 to 6.04 ) ; absence of dehydration ( weight , 3 ; OR , 3.81 ; 95 % CI , 1.89 to 7.73 ) ; and age less than 60 years ( weight , 2 ; OR , 2.45 ; 95 % CI , 1.51 to 4.01 ) . On the validation set , a Multinational Association for Supportive Care in Cancer risk-index score > /= 21 identified low-risk patients with a positive predictive value of 91 % , specificity of 68 % , and sensitivity of 71 % . CONCLUSION The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective BACKGROUND We tested the oral mammalian target of rapamycin ( mTOR ) inhibitor everolimus in addition to paclitaxel in patients with HER2-negative tumours not responding to initial neoadjuvant cytotoxic and anti-angiogenic treatment . METHODS Patients with primary HER2-negative tumours received four neoadjuvant cycles of epirubicin/cyclophosphamide ( EC ) with or without bevacizumab . Patients without clinical response were r and omised to receive weekly paclitaxel ( 80 mg/m(2 ) ) with or without everolimus ( 5 mg p.o . daily , after a step-wise dose-escalation starting from 2.5 mg bid ) for 12 weeks before surgery . To detect an increase in pathological complete response ( pCR ; ypT0 ypN0 ) from 5 % to 12.1 % ( odds ratio 2.62 ) 566 patients had to be recruited . The trial was stopped prematurely due to completion of accrual in the main study . FINDINGS Of 1948 patients initially starting neoadjuvant treatment 403 were r and omised . A total of 18 ( 4.6 % ) patients , 7 ( 3.6 % ) treated with paclitaxel and everolimus and 11 ( 5.6 % ) treated with paclitaxel alone had a pCR ( odds ratio 0.36 ( OR ) ( 95 % confidence interval ( CI ) , 0.24 - 1.6 ) p=0.34 ) . Overall response rate in breast and lymph nodes at surgery was 52.2 % after paclitaxel plus everolimus and 61.7 % after paclitaxel alone ( p=0.063 ) . Breast conserving treatment was performed in 54.4 % of patients with the combination treatment and 61.9 % with paclitaxel alone ( p=0.20 ) . Mucosal inflammation , thrombocytopenia , neutropenia , infection , and skin rash were more frequent when everolimus was added to paclitaxel . INTERPRETATION Neoadjuvant therapy with everolimus and paclitaxel for patients with HER2-negative disease unresponsive to EC with or without bevacizumab did not improve the pCR rate . Long-term outcome is awaited . FUNDING Novartis , Roche , and Sanofi-Aventis Primary chemotherapy ( PC ) is becoming an accepted practice to treat large tumors to avoid mastectomies and as a surrogate of outcome Goals of workNeutropenia is a life-threatening , dose-limiting toxicity of many chemotherapy regimens . The goals of this study were to assess the incidence and risk of chemotherapy-induced neutropenia , febrile neutropenia ( FN ) and dose limitations in breast cancer and lymphoma patients undergoing chemotherapy in Europe . Patients and methods Four hundred forty-four breast cancer and 305 lymphoma patients undergoing chemotherapy at 66 practice s in five European countries participated in this prospect i ve , observational study . Predictors of impaired chemotherapy delivery were investigated using a logistic regression model . Main results In breast cancer , FN incidence was low ( 6 % ) ; however , grade 4 neutropenia was frequent ( 34 % ) . Lymphoma patients experienced higher incidences of FN ( non-Hodgkin lymphoma ( NHL ) 22 % ; Hodgkin lymphoma ( HL ) 15 % ) and grade 4 neutropenia ( NHL 54 % ; HL 40 % ) . For both diseases , FN and grade 4 neutropenia were associated with low relative dose intensity ( RDI ) . Multivariate regression models indicated that first cycle FN , age ≥ 65 years and Eastern Co-operative Oncology Group > 1 were associated with low RDI in breast cancer and lymphoma , while colony-stimulating factor ( CSF ) primary prophylaxis appeared to be protective in lymphoma only . Primary CSF prophylaxis was provided to 9 % of breast cancer , 28 % of NHL and 19 % of HL patients . Conclusions Neutropenia and low RDI remain serious problems in both breast cancer and lymphoma population s undergoing chemotherapy . Several risk factors which can trigger reduced chemotherapy delivery were identified . These results can support physicians in identifying patients most at risk of receiving impaired chemotherapy delivery who would benefit from suitable preventive measures We aim ed to determine the efficacies of a non-anthracycline-containing regimen , docetaxel/capecitabine ( TX ) , in comparison with an anthracycline-containing regimen , doxorubicin/cyclophosphamide ( AC ) , as primary chemotherapy for node-positive early stage breast cancer . In this phase-III single center r and omized study , we r and omized 209 women with axillary node positive , stage II/III breast cancer to receive four cycles of either TX or AC followed by surgery and cross-over to the other treatment as an adjuvant therapy . The primary endpoint was tumor pathologic complete response ( pCR ) . Clinical response rates , toxicity profiles , disease free survival ( DFS ) , and overall survival were secondary objectives . In total , 204 patients had clinical and radiological evaluation of response , and underwent surgery . Compared with AC , TX increased pCR in primary tumors ( 21 % vs. 10 % , respectively , P = 0.024 ) and clinical response ( 84 % vs. 65 % , P = 0.003 ) . TX was associated with less nausea and vomiting , but more stomatitis , diarrhea , myalgia , and skin/nail changes than AC . With a median follow-up of 37 months , there was no significant difference in DFS by treatment groups ( P = 0.932 ) . Fewer patients developed recurrence who achieved pCR in lymph node ( LN ) ( P = 0.025 ; hazard ratio , 0.189 ; 95 % CI , 0.044–0.815 ) in the multivariate analysis . TX showed superior efficacies to AC with increased pathologic and clinical complete response rates . Although these findings did not translate into a gain in DFS , the patients who achieved pCR in LN developed significantly less recurrence Purpose The TEXAS ( Taxotere ® EXperience with Anthracyclines Study ) study examined docetaxel in combination with an anthracycline , as first line treatment of metastatic breast cancer ( MBC ) , in everyday practice , and compared the findings with a r and omised controlled trial . Methods Four hundred and seventy patients were registered on the TEXAS trial . Patients were assigned , according to treating clinician ’s discretion , to either doxorubicin 50 mg/m2 or epirubicin 75 mg/m2 both given day1 15 min intravenous bolus every 3 weeks , followed by docetaxel 75 mg/m2 , day 1 , 1 h intravenous infusion every 3 weeks . Results The overall response rate ( ORR ) was approximately 61 % . The main toxicity reported was neutropenia , with 75 patients ( 55 % ) in the AT group and 203 ( 61 % ) in the ET arm . Febrile neutropenia or neutropenic sepsis was reported for 32 ( 24 % ) of the AT arm and 78 ( 23 % ) of the ET arm . Conclusions This open access study demonstrates that AT or ET are highly active treatments for MBC , with similar response rates to those observed in a phase III clinical trial . This may be important for patients with rapidly progressive visceral disease . Side effects can be managed effectively with growth factors and /or prophylactic antibiotic PURPOSE To determine whether intensifying the dose of adjuvant chemotherapy improves the outcome of women with primary breast cancer and 10 or more involved axillary nodes . PATIENTS AND METHODS Patients ( n = 150 ) were r and omized to receive either four cycles of st and ard doxorubicin 60 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) every 3 weeks ( arm A ) or four courses of intensified mitoxantrone 23 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) , with filgrastim 5 g/kg/d from days 2 to 15 , every 3 weeks ( arm B ) . Disease-free survival ( DFS ) , distant disease-free survival ( DDFS ) , and overall survival ( OS ) were determined using life-table estimates . RESULTS There were no significant differences in DFS ( P = .44 ) , DDFS ( P = .67 ) , or OS ( P = .99 ) between the two groups at 5 years ; DDFS was 45 % ( arm A ) versus 50 % ( arm B ) , and DFS was 41 % versus 49 % , respectively . Five-year survival was similar in both arms ( 61 % v 60 % , respectively ) . Failure to note an intergroup difference in outcome was unrelated to relative dose-intensity . Analysis of patients with 15 or more positive nodes revealed a significant difference in 5-year DDFS ( 19 % v 49 % in arm B ; P = .01 ) . Toxicity was generally mild in both groups , with no toxic death . The incidence of febrile neutropenia was low ( 0.3 % v 3 % ) . Alopecia was less frequent in arm B ( P < .001 ) . CONCLUSION This r and omized trial confirms the feasibility of administering mitoxantrone 23 mg/m(2 ) with cyclophosphamide and filgrastim . Although there was no significant difference between conventional and intensified arms at 5 years , according to subgroup analysis , intensified treatment may decrease the risk of relapse in patients with 15 or more positive nodes compared with doxorubicin an cyclophosphamide PURPOSE Docetaxel and capecitabine , a tumor-activated oral fluoropyrimidine , show high single-agent efficacy in metastatic breast cancer ( MBC ) and synergy in pre clinical studies . This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC . PATIENTS AND METHODS Patients were r and omized to 21-day cycles of oral capecitabine 1,250 mg/m(2 ) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2 ) on day 1 ( n = 255 ) or to docetaxel 100 mg/m(2 ) on day 1 ( n = 256 ) . RESULTS Capecitabine/docetaxel result ed in significantly superior efficacy in time to disease progression ( TTP ) ( hazard ratio , 0.652 ; 95 % confidence interval [ CI ] , 0.545 to 0.780 ; P = .0001 ; median , 6.1 v 4.2 months ) , overall survival ( hazard ratio , 0.775 ; 95 % CI , 0.634 to 0.947 ; P = .0126 ; median , 14.5 v 11.5 months ) , and objective tumor response rate ( 42 % v 30 % , P = .006 ) compared with docetaxel . Gastrointestinal side effects and h and -foot syndrome were more common with combination therapy , whereas myalgia , arthralgia , and neutropenic fever/sepsis were more common with single-agent docetaxel . More grade 3 adverse events occurred with combination therapy ( 71 % v 49 % , respectively ) , whereas grade 4 events were slightly more common with docetaxel ( 31 % v 25 % with combination ) . CONCLUSION The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m(2 ) , with the manageable toxicity profile , indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m(2 ) . Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC PURPOSE Dose-dense and sequential administration of cytotoxic drugs are current approaches to improve outcomes in patients with early-stage breast cancer . METHODS This phase III study investigated 913 women with untreated operable breast cancer ( T2 - 3 , N0 - 2 , M0 ) r and omly assigned to receive either doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 every 14 days for four cycles with filgrastim support ( ADOC ) , or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 21 days followed by docetaxel 100 mg/m2 every 21 days for four cycles each ( AC-DOC ) . The primary end point was the incidence of pathologic complete ( invasive and noninvasive ) response ( pCR ) in the breast and axillary nodes . Secondary end points were predictors for pCR , clinical response , rate of breast conservation , and safety . RESULTS A pCR was achieved in 94 patients ( 10.6 % ) , but the likelihood was significantly greater with AC-DOC ( 14.3 % ; n = 63 ) than with ADOC ( 7.0 % ; n = 31 ) ( odds ratio , 2.22 ; 90 % CI , 1.52 to 3.24 ; P < .001 ) . Independent predictors of attaining a pCR included the use of sequential therapy , high tumor grade , and negative hormone receptor status . The response rates detected by palpation and by imaging were significantly higher with AC-DOC ( 85.0 % and 78.6 % , respectively ) than with ADOC ( 75.2 % and 68.6 % , respectively ; both P values < .001 ) . The rate of breast-conserving surgery was 63.4 % for AC-DOC and 58.1 % for ADOC ( P = .05 ) . Predominant grade 3/4 toxicities were leucopenia ( AC-DOC , 74.2 % ; ADOC , 53.7 % ) and neutropenia ( AC-DOC , 66.4 % ; ADOC , 44.7 % ) but were infrequently associated with fever ( AC-DOC , 4.6 % ; ADOC , 3.1 % ) . CONCLUSION Sequential AC-DOC is more effective at inducing pCR than dose-dense ADOC as preoperative treatment for patients with operable breast cancer UNLABELLED The primary objective of this open-label , two chemotherapy arm , phase 4 study was to evaluate the safety and efficacy of newly developed recombinant granulocyte colony-stimulating factor ( rG-CSF ) used to prevent neutropenia-related complications in patients with metastatic breast cancer treated with docetaxel ( 75 mg/m(2 ) ) and doxorubicin ( 50 mg/m(2 ) ) or docetaxel ( 100 mg/m(2 ) ) alone . MATERIAL AND METHODS A total of 50 patients who were treated with a maximum of 6 cycles of either docetaxel-doxorubicin ( 36 patients ) or docetaxel alone ( 14 patients ) every 21 days were recruited from 3 centers in Lithuania . All the patients received study medication rG-CSF at a dosage of 5 μg/kg per day ( Sicor Biotech UAB , Teva Group ) from day 2 of each cycle and continued for minimum 5 days or until absolute neutrophil count reached ≥1.5 × 10(9)/L. RESULTS A total of 611 adverse events were reported . Most of them were related to myelotoxic chemotherapy . Two patients withdrew due to adverse events ( neuropathy and bone pain ) . One patient died possibly because of pulmonary thromboembolism . The most frequently reported adverse events related to study drug in the docetaxel-doxorubicin and docetaxel groups were leukocytosis ( 22 % and 21 % , respectively ) , bone pain ( 19 % and 21 % , respectively ) , and headache ( 8 % and 14 % , respectively ) . The incidence of grade 4 neutropenia in both the groups was 47 % and 29 % , respectively , in all cycles and 42 % and 21 % , respectively , in cycle 1 . The incidence of febrile neutropenia was 8 % in cycle 1 and 14 % across all cycles . The mean duration of febrile neutropenia was 2.1 days ( SD , 1.9 ) in cycle 1 and 2.14 days ( SD 2.0 ) across all cycles in both the treatment groups . CONCLUSION This study provide data that the study drug rG-CSF has the expected safety and could be an efficacious medication to decrease the risk of febrile neutropenia and related complications of myelosuppressive chemotherapy in patients with metastatic breast cancer Background : Alternating administration of docetaxel and gemcitabine might result in improved time-to-treatment failure ( TTF ) and fewer adverse events compared with single-agent docetaxel as treatment of advanced breast cancer . Patients and methods : Women diagnosed with advanced breast cancer were r and omly allocated to receive 3-weekly docetaxel ( group D ) or 3-weekly docetaxel alternating with 3-weekly gemcitabine ( group D/G ) until treatment failure as first-line chemotherapy . The primary end point was TTF . Results : Two hundred and thirty-seven subjects were assigned to treatment ( group D , 115 ; group D/G , 122 ) . The median TTF was 5.6 and 6.2 months in groups D and D/G , respectively ( hazard ratio 0.85 , 95 % confidence interval 0.63–1.16 ; P = 0.31 ) . There was no significant difference in time-to-disease progression , survival , and response rate between the groups . When adverse events were evaluated for the worst toxicity encountered during treatment , there was little difference between the groups , but when they were assessed per cycle , alternating treatment was associated with fewer severe ( grade 3 or 4 ) adverse effects ( P = 0.013 ) , and the difference was highly significant for cycles when gemcitabine was administered in group D/G ( P < 0.001 ) . Conclusion : The alternating regimen was associated with a similar TTF as single-agent docetaxel but with fewer adverse effects during gemcitabine cycles PURPOSE This r and omized , noncomparative , parallel-group study was design ed to evaluate the pathologic complete response ( pCR ) rate of combined doxorubicin plus paclitaxel ( AP ) and doxorubicin plus cyclophosphamide ( AC ) as neoadjuvant chemotherapy in patients with previously untreated breast cancer who were unsuitable for conservative surgery . PATIENTS AND METHODS A total of 200 patients with T2 - 3 , N0 - 1 , M0 disease were r and omly assigned in a 2:1 ratio to receive preoperative chemotherapy with either doxorubicin 60 mg/m(2 ) plus paclitaxel 200 mg/m(2 ) as a 3-hour infusion ( AP ) or doxorubicin 60 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) ( AC ) every 3 weeks for 4 courses followed by surgery . RESULTS A pCR ( eradication of invasive carcinoma in tumor and in axillary lymph nodes ) was found in 16 % and 10 % of patients in the AP and AC arms , respectively , by study center pathologists , and in 8 % and 6 % of patients , respectively , by independent pathologists . Patients with pCRs tended to have unifocal disease , tumors with negative hormonal receptor status , and less differentiation ( Scarff , Bloom , and Richardson scale grade 3 ) . Breast-conserving surgery was performed in 58 % and 45 % of patients in the AP and AC arms , respectively . An objective clinical response was achieved in 89 % of patients in the AP arm and 70 % in the AC arm . At a median follow-up of 31 months , disease-free survival ( DFS ) was higher in patients who reached pCR versus those without pCR ( 91 % v 70 % ) . CONCLUSION The encouraging pathologic and clinical responses of patients with breast cancer after neoadjuvant chemotherapy with doxorubicin plus paclitaxel warrant additional investigation of paclitaxel in the neoadjuvant setting of breast cancer management OBJECTIVE FSK0808 is a filgrastim biosimilar . This study assessed the efficacy and safety of FSK0808 in patients with breast cancer . METHODS One hundred and four breast cancer patients undergoing chemotherapy were enrolled in the study . FSK0808 was used to treat the neutropenia experienced by the patients in the course of their chemotherapy . Efficacy was evaluated by the recovery of absolute neutrophil count following FSK0808 administration based on the duration of neutropenia in patients who received pre- or postoperative chemotherapy containing fluorouracil , epirubicin and cyclophosphamide . Adverse events were evaluated in accordance with the Common Terminology Criteria for Adverse Events version 3.0 . The incidence of febrile neutropenia and generation of an anti-granulocyte colony-stimulating factor antibody were also evaluated . RESULTS The average duration of neutropenia in Cycle 2 was 2.2 days with a st and ard deviation of 1.5 days . The upper limit of the 97.5 % one-sided confidence interval was 2.5 days and was confirmed not to exceed 3.0 days , which was defined as the threshold value of absolute neutrophil count recovery . The incidence of febrile neutropenia across all treatment cycles was 34.6 % . Observed adverse drug reactions with an incidence of > 5 % were back pain ( 60.6 % ) , bone pain ( 9.6 % ) , alanine aminotransferase increase ( 8.7 % ) , aspartate aminotransferase increase ( 5.8 % ) and arthralgia ( 5.8 % ) . Production of the anti-granulocyte colony-stimulating factor antibody was not observed in any patient during the study . CONCLUSIONS FSK0808 was safe and well tolerated in breast cancer patients undergoing chemotherapy and effectively stimulated neutrophil recovery PURPOSE Cyclophosphamide , epirubicin , and fluorouracil ( CEF ) and doxorubicin and cyclophosphamide ( AC ) followed by paclitaxel ( T ) are commonly used adjuvant regimens in women with early breast cancer . In a previous trial in women with locally advanced breast cancer , 3 months of high-dose epirubicin and cyclophosphamide ( EC ) administered every 2 weeks ( dose-dense ) was equivalent to 6 months of CEF . We hypothesized that 3 months of paclitaxel after dose-dense EC ( EC/T ) would be superior to CEF or AC/T. METHODS After lumpectomy or mastectomy , women 60 years of age or younger with axillary node-positive or high-risk node-negative breast cancer were r and omly assigned to receive CEF , EC/T , or AC/T for 6 months . This article reports the interim analysis for recurrence-free survival ( RFS ) , which was planned after 227 recurrences . Results A total of 2,104 patients were enrolled . The median follow-up is 30.4 months . Hazard ratios for recurrence are as follows : AC/T versus CEF , 1.49 ( 95 % CI , 1.12 to 1.99 ) , P = .005 ; AC/T versus EC/T , 1.68 ( 95 % CI , 1.25 to 2.27 ) , P = .0006 ; and EC/T versus CEF , 0.89 ( 95 % CI , 0.64 to 1.22 ) , P = .46 . Three-year RFS rates for CEF , EC/T , and AC/T are 90.1 % , 89.5 % , and 85.0 % , respectively . There was more febrile neutropenia with CEF ( 22.3 % ) and EC/T ( 16.4 % ) compared with AC/T ( 4.8 % ) , but more neuropathy with the last two regimens . CONCLUSION Three-weekly AC/T is significantly inferior to CEF or EC/T in terms of RFS . It is too early to detect any difference between CEF and dose-dense This trial compared 6 cycles of fluorouracil , epirubicin , and cyclophosphamide ( FEC ) with a sequential regimen of 3 cycles of FEC followed by 3 cycles of docetaxel ( FEC-D ) as adjuvant treatment for women with node-positive or/ and T3 or T4 breast cancer . Between January 2006 and January 2010 , 657 patients with operable breast cancer were r and omly assigned to either FEC every 21 days for 6 cycles , or 3 cycles of FEC followed by 3 cycles of docetaxel , both given every 21 days . Radiotherapy was m and atory for all patients who had undergone breast conserving surgery . Radiation to the chest wall , supraclavicular area , was recommended following mastectomy . Hormone-receptor – positive patients received tamoxifen for 5 years after chemotherapy . The primary end point was 5-year disease-free survival ( DFS ) . Median follow-up was 61 months . Five-year DFS rates were 74 % with FEC and 78 % with FEC-D ( P = 0.013 ) . Multivariate analysis adjusted for prognostic factors showed a 17 % reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 85 % with FEC and 89.4 % with FEC-D , demonstrating a 27 % reduction in the relative risk of death ( P = 0.014 ) . The incidence of grade 3–4 neutropenia , the need for hematopoietic growth factor , and incidence of nausea/vomiting were higher with FEC . Docetaxel was associated with more febrile neutropenia , stomatitis , edema , and nail disorders . Though rare overall , there were fewer cardiac events after FEC-D , attributable mainly to the lower anthracycline cumulative dose . Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves disease-free and overall survival in node-positive or/ and T3 or T4 breast cancer patients . Although the magnitude of the benefit observed with FEC-D , differences in the toxicity profiles of FEC and FEC-D may influence the choice of treatment for patients Early-stage breast cancer ( ESBC ) is commonly treated with myelosuppressive chemotherapy , and maintaining full-dose chemotherapy on the planned schedule is associated with improved patient outcome . Retrospective analysis of patients with ESBC treated from 1997 to 2000 showed that 56 % of patients received a relative dose intensity ( RDI ) < 85 % ( Lyman et al. , J Clin Oncol 21(24):4524–4531 , 2003 ) . To determine current practice , we evaluated treatment patterns at 24 US community- and hospital-based oncology practice s , 79 % of which participated in the previous study . Data were abstract ed from medical records of 532 patients with surgically resected ESBC ( stage I – IIIa ) treated from 2007 to 2009 , who were ≥18 years old and had completed ≥1 cycle of one of the following regimens : docetaxel + cyclophosphamide ( TC ) ; doxorubicin + cyclophosphamide ( AC ) ; AC followed by paclitaxel ( AC-T ) ; docetaxel + carboplatin + trastuzumab ( TCH ) ; or docetaxel + doxorubicin + cyclophosphamide ( TAC ) . Endpoints included RDI , dose delays , dose reductions , grade 3/4 neutropenia , febrile neutropenia ( FN ) , FN-related hospitalization , granulocyte colony-stimulating factor ( G-CSF ) use , and antimicrobial use . In this study , TC was the most common chemotherapy regimen ( 42 % ) , and taxane-based chemotherapy regimens were more common relative to the previously published results ( 89 vs < 4 % ) . Overall , 83.8 % of patients received an RDI ≥85 % , an improvement over the previous study where 44.5 % received an RDI ≥85 % . Other changes seen between this and the previous study included a lower incidence of dose delays ( 16 vs 25 % ) and dose reductions ( 21 vs 37 % ) and increased use of primary prophylactic G-CSF ( 76 vs ~3 % ) . Here , 40 % of patients had grade 3/4 neutropenia , 3 % had FN , 2 % had an FN-related hospitalization , and 30 % received antimicrobial therapy ; these measures were not available in the previously published results . Though RDI was higher here than in the previous study , 16.2 % of patients still received an RDI < 85 % . Underst and ing factors that contribute to reduced RDI may further improve chemotherapy delivery , and ultimately , patient outcomes PURPOSE The combination of doxorubicin and cyclophosphamide ( AC ) is a st and ard adjuvant chemotherapy regimen . Studies of docetaxel and cyclophosphamide ( TC ) in metastatic breast cancer ( MBC ) showed promise in MBC . In 1997 , we initiated a r and omized adjuvant trial of TC compared with st and ard-dose AC with a primary end point of disease-free survival ( DFS ) . PATIENTS AND METHODS Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor . Between June 1997 and December 1999 , 1,016 patients were r and omly assigned to four cycles of either st and ard-dose AC ( 60 and 600 mg/m2 , respectively ; n = 510 ) or TC ( 75 and 600 mg/m2 , respectively ; n = 506 ) , administered intravenously every 3 weeks as adjuvant chemotherapy . Radiation therapy ( as indicated ) and tamoxifen , for patients with hormone receptor-positive disease , were administered after completion of chemotherapy . RESULTS Both treatment groups ( TC and AC ) were well balanced with respect to major prognostic factors . Patients were observed through 2005 for a median of 5.5 years . At 5 years , DFS rate was significantly superior for TC compared with AC ( 86 % v 80 % , respectively ; hazard ratio [ HR ] = 0.67 ; 95 % CI , 0.50 to 0.94 ; P = .015 ) . Overall survival rates for TC and AC were 90 % and 87 % , respectively ( HR = 0.76 ; 95 % CI , 0.52 to 1.1 ; P = .13 ) . More myalgia , arthralgia , edema , and febrile neutropenia occurred on the TC arm ; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure . CONCLUSION At 5 years , TC was associated with a superior DFS and a different toxicity profile compared with AC PURPOSE Anthracyclines , taxanes , and alkylating agents are among the most active agents in treatment of adjuvant breast cancer ( BC ) , but the optimal schedule for their administration is unknown . We performed an adjuvant trial to compare the sequential regimen of doxorubicin with cyclophosphamide ( AC ) followed by docetaxel ( ie , AC > T ) with the combination regimen of TAC . PATIENTS AND METHODS Women with node-positive , human epidermal growth factor receptor 2-nonamplified , operable BC were stratified by number of axillary nodes and hormone receptor status and were r and omly assigned to adjuvant chemotherapy with six cycles of TAC ( 75/50/500 mg/m² every 3 weeks ) or four cycles of AC ( 60/600 mg/m² every 3 weeks ) followed by four doses of docetaxel at 100 mg/m² every 3 weeks ( AC > T ) . After completion of chemotherapy , radiation therapy was given as indicated , and patients with hormone receptor ( HR ) -positive disease received adjuvant hormonal therapy with tamoxifen and /or aromatase inhibitors . RESULTS In 30 months , 3,298 patients were enrolled ( n = 1,649 in each arm ) . The major baseline characteristics were well balanced between the groups . At a median follow-up of 65 months , estimated 5-year disease-free survival rates were 79 % in both groups ( log-rank P = .98 ; hazard ratio [ HR ] , 1.0 ; 95%CI , 0.86 to 1.16 ) , and 5-year overall survival rates for both arms were 88 % and 89 % , respectively ( log-rank P = .37 ; HR , 0.91 ; 95 % CI , 0.75 to 1.11 ) . TAC was associated with more febrile neutropenia and thrombocytopenia , and AC > T was associated with more sensory neuropathy , nail changes , and myalgia . The incidence of neutropenic infection was similar in both groups . CONCLUSION The sequential and combination regimens incorporating three drugs were equally effective but differed in toxicity profile PURPOSE To evaluate whether preoperative neoadjuvant chemotherapy in patients with primary operable breast cancer results in better overall survival ( OS ) and relapse-free survival rates and whether preoperative chemotherapy permits more breast-conserving surgery procedures than postoperative chemotherapy . PATIENTS AND METHODS Six hundred ninety-eight breast cancer patients ( T1c , T2 , T3 , T4b , N0 to 1 , and M0 ) were enrolled onto a r and omized phase III trial that compared four cycles of fluorouracil , epirubicin , and cyclophosphamide administered preoperatively versus the same regimen administered postoperatively ( the first cycle administered within 36 hours after surgery ) . Patients were followed up for OS , progression-free survival ( PFS ) , and locoregional recurrence ( LRR ) . RESULTS At a median follow-up of 56 months , there was no significant difference in terms of OS ( hazards ratio , 1.16 ; P = .38 ) , PFS ( hazards ratio , 1.15 ; P = .27 ) , and time to LRR ( hazards ratio , 1.13 ; P = .61 ) . Fifty-seven patients ( 23 % ) were downstaged by the preoperative chemotherapy , whereas 14 patients ( 18 % ) underwent mastectomy and not the planned breast-conserving therapy . CONCLUSION The use of preoperative chemotherapy yields similar results in terms of PFS , OS , and locoregional control compared with conventional postoperative chemotherapy . In addition , preoperative chemotherapy enables more patients to be treated with breast-conserving surgery . Because preoperative chemotherapy does not improve disease outcome compared with postoperative chemotherapy , future trials should involve quality -of-life studies to investigate whether patients will benefit from this treatment modality PURPOSE To evaluate whether a relationship exists between docetaxel dose and clinical response in the treatment of patients with advanced breast cancer . PATIENTS AND METHODS Patients whose cancer had progressed after one prior chemotherapy regimen for advanced breast cancer or had recurred during or within 6 months of adjuvant chemotherapy were r and omly assigned to docetaxel 60 , 75 , or 100 mg/m2 intravenously every 3 weeks . RESULTS Five hundred twenty-seven patients were r and omly assigned ( intent to treat [ ITT ] ) , and 524 were assessable for toxicity . In the population assessable for efficacy ( n = 407 ) , logistic regression analysis showed that increasing docetaxel dose was significantly associated with higher response rate ( P = .007 ) and improved time to progression ( TTP ; P = .014 ) . In the ITT analysis , a significant dose-response relationship was observed for tumor response ( P = .026 ) but not for TTP ( P = .067 ) . The incidences of most hematologic and nonhematologic toxicities were related to increasing dose , with grade 3 to 4 neutropenia occurring in 76.4 % , 83.7 % , and 93.4 % and febrile neutropenia occurring in 4.7 % , 7.4 % , and 14.1 % of patients administered the 60 , 75 , and 100 mg/m2 doses , respectively . One death was considered treatment related . CONCLUSION A relationship between increasing dose of docetaxel and increased tumor response was observed across the dose range of 60 to 100 mg/m2 every 3 weeks . Toxicities were related to increasing dose . Depending on the therapy goal , any of the doses studied may be appropriate for second-line treatment of advanced breast cancer CONTEXT Adjuvant chemotherapy with new cytotoxic agents for breast cancer must be properly assessed for toxicity . OBJECTIVE To describe adverse events associated with adjuvant chemotherapy for breast cancer , which led to premature termination of a clinical trial . DESIGN , SETTING , AND PATIENTS We conducted a prospect i ve r and omized multicenter study ( Reposant sur des Arguments Pronostiques et Predictifs [RAPP]-01 ) to compare the effectiveness of 2 chemotherapy regimens . Patients ( women aged 18 - 70 years ) had primary unilateral breast cancer and either a moderate number of positive axillary lymph nodes ( < or =3 ) or no positive axillary lymph nodes ( N0 ) , but were at a high risk of relapse . Patients were treated at 11 French cancer referral centers from June 1999 through January 2003 . Primary prophylaxis for febrile neutropenia was not recommended in the study protocol . INTERVENTIONS Doxorubicin , 50 mg/m2 , plus docetaxel , 75 mg/m2 , or doxorubicin , 60 mg/m2 , plus cyclophosphamide , 600 mg/m2 , given postoperatively for 4 courses . MAIN OUTCOME MEASURES The main end point was the disease-free survival rate at 5 years , as estimated using the Kaplan-Meier product limit method . Secondary end points included safety , which is the focus of this article , and overall survival . RESULTS A total of 627 women were enrolled . Median follow-up is currently too short ( 24 months ) to analyze the primary end point . The trial was terminated prematurely when 2 deaths related to drug toxicity and 1 case of perforative peritonitis occurred among patients with febrile neutropenia , all in the doxorubicin-docetaxel group . The incidence of febrile neutropenia was significantly higher with the doxorubicin-docetaxel regimen ( 40.8 % ) than with the doxorubicin-cyclophosphamide regimen ( 7.1 % ) ( P<.001 ) . CONCLUSIONS A high risk of life-threatening complications associated with the doxorubicin-docetaxel regimen was found in this open-label controlled trial . The doxorubicin-docetaxel combination should not be considered as an alternative to the doxorubicin-cyclophosphamide regimen outside carefully design ed studies that include primary prophylaxis for febrile neutropenia The objective of this study was to compare the antitumor activity of single-agent paclitaxel ( Taxol ; Bristol-Myers Squibb Company , Princeton , NJ ) with that of the 5-fluorouracil/doxorubicin/cyclophosphamide ( FAC ) combination by evaluating the extent of residual disease in the breast and regional lymph nodes of patients with breast cancer following four cycles of induction chemotherapy . Patients with histologically confirmed invasive but noninflammatory carcinoma of the breast stages T2 - 3 , N0 - 1 , M0 were eligible to enter the study . Patients were treated with four cycles of either FAC or single-agent paclitaxel before local therapy . Following local therapy , treatment of the two arms was identical . Of 104 operable breast cancer patients who were treated with either regimen , 78 were evaluable for response to preoperative chemotherapy and had undergone local therapy . Age , TNM classification , and estrogen receptor status of the patients were similar in the two groups . Following induction chemotherapy , the extent of disease in the breast and the distribution and number of positive nodes were similar between the two treatment arms . Disease progressed in two patients in the FAC arm and in none in the paclitaxel arm during the induction phase of therapy . A higher fraction of patients had neutropenic fever during the paclitaxel treatment . Initial data from this ongoing r and omized study show that paclitaxel alone has comparable anticancer activity with FAC in patients with early breast cancer . The degree of cytoreduction was similar with both induction therapies PURPOSE ABI-007 , the first biologically interactive albumin-bound paclitaxel in a nanameter particle , free of solvents , was compared with polyethylated castor oil-based st and ard paclitaxel in patients with metastatic breast cancer ( MBC ) . This phase III study was performed to confirm pre clinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with st and ard paclitaxel . PATIENTS AND METHODS Patients were r and omly assigned to 3-week cycles of either ABI-007 260 mg/m(2 ) intravenously without premedication ( n = 229 ) or st and ard paclitaxel 175 mg/m(2 ) intravenously with premedication ( n = 225 ) . RESULTS ABI-007 demonstrated significantly higher response rates compared with st and ard paclitaxel ( 33 % v 19 % , respectively ; P = .001 ) and significantly longer time to tumor progression ( 23.0 v 16.9 weeks , respectively ; hazard ratio = 0.75 ; P = .006 ) . The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with st and ard paclitaxel ( 9 % v 22 % , respectively ; P < .001 ) despite a 49 % higher paclitaxel dose . Febrile neutropenia was uncommon ( < 2 % ) , and the incidence did not differ between the two study arms . Grade 3 sensory neuropathy was more common in the ABI-007 arm than in the st and ard paclitaxel arm ( 10 % v 2 % , respectively ; P < .001 ) but was easily managed and improved rapidly ( median , 22 days ) . No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time . CONCLUSION ABI-007 demonstrated greater efficacy and a favorable safety profile compared with st and ard paclitaxel in this patient population . The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC PURPOSE To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide ( AC ) with doxorubicin and docetaxel ( AD ) as primary chemotherapy in women with primary or locally advanced breast cancer . PATIENTS AND METHODS Eligible patients with histologically proven breast cancer with primary tumors > /= 3 cm , inflammatory or locally advanced disease , and no evidence of metastases were r and omly assigned to receive a maximum of six cycles of either doxorubicin ( 60 mg/m(2 ) ) plus cyclophosphamide ( 600 mg/m(2 ) ) administered intravenously ( IV ) every 3 weeks or doxorubicin ( 60 mg/m(2 ) ) plus docetaxel ( 75 mg/m(2 ) ) IV every 3 weeks , followed by surgery on completion of chemotherapy . Results A total of 363 patients were r and omly assigned to AC ( n = 180 ) or AD ( n = 183 ) . A complete clinical response was observed in 17 % and 20 % of patients treated with AC and AD , respectively ( P = .42 ) . Overall ( complete and partial ) clinical response rates for AC and AD were 61 % and 70 % , respectively ( P = .06 ) . There was no significant difference in either the pathologic complete response rates in the breast with AC ( 24 % ) and AD ( 21 % ; P = .61 ) or in the number of patients with positive axillary nodes at surgery with AC ( 61 % ) and AD ( 66 % ; P = .28 ) . At a median follow-up of 32 months , there is no significant difference between the two groups for the number of relapses . CONCLUSION In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer , our data do not suggest a benefit for simultaneous AD over AC Aims and background We investigated the efficacy and tolerability of two doses of paclitaxel , 175 mg/m2 and 135 mg/m2 , over a 3-hr infusion , without prophylactic G-CSF , in heavily pretreated patients with anthracycline-resistant breast cancer . Although paclitaxel may share with anthracyclines a common mechanism of drug resistance , there is evidence that the two drugs are not completely cross resistant . Methods From July 1994 to January 1996 , 42 patients were treated every 3 weeks , for a maximum of 6 cycles ; paclitaxel dose was established according to pretreatment extension . Results In 41 assessable patients we observed 9 partial responses , for an overall response rate of 22 % ( 95 % CI , 10–34 % ) . There was no difference in response rate between the two dose levels . Median duration of response was 9 months , median time to progression 5 months , and median survival 9 months . The dose-limiting toxicity was neutropenia , which was grade 3–4 in 40 % ( 135 mg/m2 ) and 62 % ( 175 mg/m2 ) of the patients ( P = 0.28 ) ; neutropenic fever occurred in 24 % of the patients , without significant differences between the two dose levels . Other toxicity was mild to moderate . Conclusions Paclitaxel at doses of 175 mg/m2 or 135 mg/m2 is active and well tolerated in advanced breast cancer patients resistant to anthracyclines . The prophylactic use of colony-stimulating factors seems appropriate in heavily pretreated patients given the higher dose level PURPOSE To compare the efficacy of chemotherapy versus that of tamoxifen plus ovarian suppression in pre-/perimenopausal estrogen receptor-positive patients with early breast cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive either six cycles of a st and ard regimen of cyclophosphamide 100 mg/m(2 ) orally days 1 to 14 , methotrexate 40 mg/m(2 ) intravenously ( IV ) days 1 and 8 , and fluorouracil 600 mg/m(2 ) IV days 1 and 8 ( CMF ) , with all drugs restarted on day 29 , or 5 years of tamoxifen , 30 mg/d , plus ovarian suppression with surgical oophorectomy , ovarian irradiation , or monthly goserelin 3.6-mg injections . Disease-free survival was the main study end point . Overall survival and toxicity were additional end points . RESULTS Between 1989 and 1997 , 120 patients were assigned to CMF and 124 to tamoxifen and ovarian suppression ( oophorectomy , n = 6 ; ovarian irradiation , n = 31 ; and goserelin injections , n = 87 ) . At the time of analysis ( median follow-up time , 76 months ; range , 9 to 121 months ) , 82 patients had relapsed and 39 had died . No difference between groups had emerged with respect to either disease-free or overall survival . Treatments were comparable even in respect to age , tumor size , and nodal status , although a nonsignificant trend favored patients with poorly differentiated tumors treated with CMF . Leukopenia , nausea , vomiting , stomatitis , and alopecia were significantly more common in patients treated with CMF . There were few patients who developed benign gynecologic changes in either group , and numbers were comparable . CONCLUSION The combination of tamoxifen with ovarian suppression seems to be safe and to yield comparable results relative to st and ard CMF BACKGROUND Among breast cancer patients , nonresponse to initial neoadjuvant chemotherapy is associated with unfavorable outcome . We compared the response of nonresponding patients who continued the same treatment with that of patients who switched to a well-tolerated non-cross-resistant regimen . METHODS Previously untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/m(2 ) , doxorubicin at 50 mg/m(2 ) , and cyclophosphamide at 500 mg/m(2 ) per day ( TAC ) . Patients whose tumors did not decrease in size by at least 50 % were r and omly assigned to four additional cycles of TAC or to four cycles of vinorelbine at 25 mg/m(2 ) and capecitabine at 2000 mg/m(2 ) ( NX ) . The outcome was sonographic response , defined as a reduction in the product of the two largest perpendicular diameters by at least 50 % . A difference of 10 % or less in the sonographic response qualified as noninferiority of the NX treatment . Pathological complete response was defined as no invasive or in situ residual tumor masses in the breast and lymph nodes . Toxic effects were assessed . All statistical tests were two-sided . RESULTS Of 2090 patients enrolled in the GeparTrio study , 622 ( 29.8 % ) who did not respond to two initial cycles of TAC were r and omly assigned to an additional four cycles of TAC ( n = 321 ) or to four cycles of NX ( n = 301 ) . Sonographic response rate was 50.5 % for the TAC arm and 51.2 % for the NX arm . The difference of 0.7 % ( 95 % confidence interval = -7.1 % to 8.5 % ) demonstrated noninferiority of NX ( P = .008 ) . Similar numbers of patients in both arms received breast-conserving surgery ( 184 [ 57.3 % ] in the TAC arm vs 180 [ 59.8 % ] in the NX arm ) and had a pathological complete response ( 5.3 % vs 6.0 % ) . Fewer patients in the NX arm than in the TAC arm had hematologic toxic effects , mucositis , infections , and nail changes , but more had h and -foot syndrome and sensory neuropathy . CONCLUSION Pathological complete responses to both regimens were marginal . Among patients who did not respond to the initial neoadjuvant TAC treatment , similar efficacy but better tolerability was observed by switching to NX than continuing with TAC PURPOSE The National Surgical Adjuvant Breast and Bowel Project Protocol B-27 was design ed to determine the effect of adding docetaxel after four cycles of preoperative doxorubicin and cyclophosphamide ( AC ) on clinical and pathological response rates and on disease-free and overall survival of women with operable breast cancer . PATIENTS AND METHODS Women ( N = 2,411 ) with operable primary breast cancer were r and omly assigned to receive either four cycles of preoperative AC followed by surgery ( group I ) , or four cycles of AC followed by four cycles of docetaxel , followed by surgery ( group II ) , or four cycles of AC followed by surgery and then four cycles of docetaxel ( group III ) . Clinical and pathologic tumor responses to preoperative therapy were assessed . RESULTS Mean tumor size ( 4.5 cm ) and other key characteristics were evenly balanced among the three treatment arms . Grade 4 toxicity was observed in 10.3 % of 2,400 patients during AC treatment , and in 23.4 % of 1584 patients during docetaxel treatment . Compared to preoperative AC alone , preoperative AC followed by docetaxel increased the clinical complete response rate ( 40.1 % v 63.6 % ; P < .001 ) , the overall clinical response rate ( 85.5 % v 90.7 % ; P < .001 ) , the pathologic complete response rate ( 13.7 % v 26.1 % ; P < .001 ) , and the proportion of patients with negative nodes ( 50.8 % v 58.2 % ; P < .001 ) . Pathologic primary breast tumor response was a significant predictor of pathologic nodal status ( P < .001 ) . CONCLUSION The addition of four cycles of preoperative docetaxel after four cycles of preoperative AC significantly increased clinical and pathologic response rates for operable breast cancer 109 Background : Toxicity related hospitalizations during chemotherapy are poorly reported in the literature . We sought to compare " real world " versus clinical trial rates of hospitalizations among patients with metastatic non-small cell lung cancer ( mNSCLC ) receiving chemotherapy . We hypothesised that hospitalization rates in real life patients would be significantly higher . METHODS We conducted a systematic review of Medline and EMBASE ( 1946-June 2013 ) to identify articles reporting hospitalization rates during chemotherapy in patients with cancer . Both observational studies and clinical trials were eligible . This report focuses on patients with mNSCLC receiving palliative chemotherapy as data was available for this clinical scenario in both the observational and clinical trial setting , allowing comparison . Study results were abstract ed using a st and ardised form . Summary statistics were used to describe results and the chi-square test used to compare hospitalization rates . RESULTS The search identified 61 articles ( all published after 1987 ) , of which 16 were clinical trials and 45 were observational ( " real world " ) studies . Nine studies examined chemotherapy in mNSCLC - four observational studies and five r and omised trials . The four observational studies included 7,456 patients ; three included patients on any chemotherapy while the other focused on doublet regimens . Of the five r and omised trials which included 3,962 patients , three treated patients with platinum doublets and two used single-agent chemotherapy . The real life cohort was older ( 70 years vs. 62 years ) . The aggregate hospitalization rate among real life patients was significantly higher than among trial patients ( 49 % vs. 16 % , OR=7.7 , 95 % CI 7 - 8.5 , p-value < 0.0001 ) . Performance status and type of chemotherapy were associated with hospitalization during chemotherapy in clinical trials while type of chemotherapy was a risk factor in observational studies . CONCLUSIONS Clinical trials in mNSCLC consistently report lower rates of hospitalization than real life cohorts of patients undergoing similar therapies but very few clinical trials report this information R and omized controlled trials - the gold st and ard for clinical drug evaluation -can't always predict adverse events in real-world setting s. For the new cancer therapies , observational cohort studies ( OCSs ) can help evaluate their effects in broader population s and provide valuable information for future clinical trials The purpose of this study is to evaluate the efficacy and safety of docetaxel plus cyclophosphamide(TC ) compared with docetaxel , anthracycline , and cyclophosphamide(TEC ) in neoadjuvant treatment of triple negative or HER2 positive breast cancer . Eligible breast cancer patients were r and omized to receive six cycles of TC or TEC . The primary end point was pathological complete remission ( pCR ) . Secondary end points included safety , clinical response rate , and survival outcome . One hundred and two patients were initially r and omized and 96 patients were available for efficacy analysis . 96.9 % patients were treated with epirubicin as an anthracycline agent . pCR rates were 6.8 % ( 3/45 ) and 17.6 % ( 9/51 ) in TC and TEC group , respectively , P = 0.113 . After a mean follow up of 20 ( 3–36 ) months , non-anthracycline-containing TC regimen treatment result ed in a worse event free survival ( adjusted hazard ratio [ HR ] 2.42 ; 95 % CI1.11–5.30 ) and disease-free survival ( HR 2.85 ; 95 % CI1.21–6.74 ) compared with TEC regimen , which was more apparent in triple negative subtype . Severe adverse event rates were similar , except that patients treated with TEC had a higher rate of neutropenia and leucopenia . TEC treatment had a superior survival outcome and trend of higher pCR rate compared with TC in this trial setting , especially in triple negative subtype , which deserves further validation A prospect i ve cohort study was undertaken to develop and vali date a risk model for neutropenic complications in cancer patients receiving chemotherapy BACKGROUND St and ard adjuvant chemotherapy regimens for patients with node positive ( N+ ) breast cancer consisted of anthracycline followed by taxane . The European Association for Research in Oncology embarked in 2000 on a phase III trial comparing 6 cycles of FEC100 versus 4 FEC100 followed by 4 Taxol . Primary end-point was disease free survival . Secondary end-points were overall survival , local recurrence free interval , metastases free interval and safety . PATIENTS AND METHODS Between March 2000 and December 2002 , 837 patients were r and omised between 6FEC100 for 6 cycles ( 417 patients ) or FEC100 for 4 cycles then Taxol 175mg/m(2)/3 weeks for 4 cycles ( 4FEC100 - 4 T ) ( 420 patients ) . One thous and patients had been planned initially but the trial was closed earlier due to slow accrual . RESULTS Hazard ratios ( HRs ) were 0.99 for disease-free survival ( DFS ) ( 95%CI : 0.77 - 1.26 ; p=0.91 ) , and 0.85 for overall survival ( OS ) ( 95%CI : 0.62 - 1.15 ; p=0.29 ) . Nine-year DFS were 62.9 % versus 62.5 % for 6FEC100 and 4FEC100 - 4 T , respectively . Nine-year OS were 73.9 % versus 77 % for 6FEC100 and 4FEC100 - 4 T , respectively . Toxicity analyses based on 803 evaluable patients showed that overall grade 3 - 4 toxicities were similar in both arms ( 63 % versus 58 % for 6FEC100 arm and 4FEC100 - 4 T arm , respectively ; p=0.16 ) . CONCLUSION In this trial replacing the last 2 FEC100 cycles of 6FEC100 regimen by 4 Taxol does not lead to a discernable DFS or OS advantage . The lack of a significant difference between the r and omised treatment arms may however be due to a lack of power of this trial to detect small , yet clinical ly worthwhile , treatment benefits |
12,435 | 22,588,359 | Interventions that train parents may be a useful approach to alleviate behavioral and emotional disturbances after pediatric TBI .
Some evidence suggests that these interventions may help to improve parenting skill and adjustment .
However , all identified studies included interventions with multiple treatment components , so the effects attributable to parent training alone remain undetermined . | OBJECTIVE To evaluate the efficacy of parenting interventions on child and parent behavioral and emotional outcomes for parents of children with traumatic brain injury ( TBI ) . | The outcomes of a r and omized clinical trial of a new behavioral family intervention , Stepping Stones Triple P , for preschoolers with developmental and behavior problems are presented . Forty-eight children with developmental disabilities participated , 27 r and omly allocated to an intervention group and 20 to a wait-list control group . Parents completed measures of parenting style and stress , and independent observers assessed parent-child interactions . The intervention was associated with fewer child behavior problems reported by mothers and independent observers , improved maternal and paternal parenting style , and decreased maternal stress . All effects were maintained at 6-month follow-up The purpose of this study was to provide an experimental test of the theory of change put forth by A. T. Beck , A. J. Rush , B. F. Shaw , and G. Emery ( 1979 ) to explain the efficacy of cognitive-behavioral therapy ( CT ) for depression . The comparison involved r and omly assigning 150 out patients with major depression to a treatment focused exclusively on the behavioral activation ( BA ) component of CT , a treatment that included both BA and the teaching of skills to modify automatic thoughts ( AT ) , but excluding the components of CT focused on core schema , or the full CT treatment . Four experienced cognitive therapists conducted all treatments . Despite excellent adherence to treatment protocol s by the therapists , a clear bias favoring CT , and the competent performance of CT , there was no evidence that the complete treatment produced better outcomes , at either the termination of acute treatment or the 6-month follow-up , than either component treatment . Furthermore , both BA and AT treatments were just as effective as CT at altering negative thinking as well as dysfunctional attributional styles . Finally , attributional style was highly predictive of both short- and long-term outcomes in the BA condition , but not in the CT condition Objective : To examine the efficacy of teen online problem solving ( TOPS ) in improving executive function ( EF ) deficits following traumatic brain injury ( TBI ) in adolescence . Methods : Families of adolescents ( aged 11–18 years ) with moderate to severe TBI were recruited from the trauma registry of 2 tertiary-care children 's hospitals and then r and omly assigned to receive TOPS ( n = 20 ) , a cognitive-behavioral , skill-building intervention , or access to online re sources regarding TBI ( Internet re source comparison ; n = 21 ) . Parent and teen reports of EF were assessed at baseline and a posttreatment follow-up ( mean = 7.88 months later ) . Results : Improvements in self-reported EF skills were moderated by TBI severity , with teens with severe TBI in the TOPS treatment reporting significantly greater improvements than did those with severe TBI in the Internet re source comparison . The treatment groups did not differ on parent ratings of EF at the follow up . Conclusions : Findings suggest that TOPS may be effective in improving EF skills among teens with severe TBI Objective To describe a family-centered problem-solving intervention ( FPS ) for pediatric traumatic brain injury ( TBI ) , and to assess the efficacy of the intervention in a r and omized clinical trial . Participants Families of 32 school-aged children with moderate to severe TBI r and omly assigned to FPS or usual care ( UC ) group . Main Outcome Measures Child Behavior Checklist , Brief Symptom Inventory , Conflict Behavior Question naire . InterventionS even-session problem-solving/skill-building intervention delivered over a 6-month period for the participating families . Results Parents in the FPS group reported significantly greater improvements in their children in internalizing symptoms , anxiety/depression , and withdrawal than did parents in the UC comparison group . Conclusions FPS holds promise for reducing child behavior problems , the most common and persistent sequelae of TBI Primary objectives : To explore the relative effectiveness of clinician-delivered vs family-supported interventions for children with chronic impairment after TBI . Research design : R and omized controlled clinical trial . Methods and procedures : Children aged 5–12 years in the chronic phase of their recovery were r and omly assigned to the clinician-delivered or to the family-supported intervention group ; both sample s received intensive services for 1 year ; physical outcome was measured by the SARAH scales , cognitive outcome by the WISC-III . Main outcomes and results : Parents in the family-supported intervention sample efficiently acquired the skills needed to deliver physical and cognitive interventions within the context of everyday routines of the child 's life at home ; family education level was not a factor . Although both groups demonstrated improvements , only the children in the family-supported intervention group demonstrated statistically significant — and clinical ly important — improvements on both outcome measures . Conclusions : This RCT provides compelling evidence for organizing cognitive and physical interventions and supports for children with TBI around the everyday routines of their lives , with intensive supports for their families This study examined whether an online problem-solving intervention could improve parental adjustment following pediatric traumatic brain injury ( TBI ) . Families of children with moderate-to-severe TBI were recruited from the trauma registry of a large children 's hospital and r and omly assigned to receive online family problem solving therapy ( FPS ; n = 20 ) or Internet re sources ( IRC ; n = 20 ) in addition to usual care . The FPS group reported significantly less global distress , depressive symptoms , and anxiety at follow-up than did the IRC group after controlling for baseline symptoms . The FPS group also reported significant improvements in problem-solving skills , although the groups did not differ significantly at follow-up . Findings suggest that an online , skill-building approach can be effective in facilitating parental adaptation after TBI Whilst the Triple P Positive Parenting Program has a large evidence base ( S and ers , Clinical Child and Family Psychology Review 2:71–90 , 1999 ; S and ers , Journal of Consulting and Clinical Psychology 68:624–640 , 2000 ) and preliminary evidence indicates that Stepping Stones Triple P is also efficacious ( Roberts , Journal of Clinical Child and Adolescent Psychology , 35(2):180–193 , 2006 ) , to date Stepping Stones has not been evaluated with the ASD population . Fifty-nine families with a child with ASD aged between 2 and 9 participated in this r and omized controlled trial . The results demonstrate significant improvements in parental reports of child behaviour and parenting styles with the treatment effects for child behaviour , parental over reactivity and parental verbosity being maintained at follow-up 6 months later . Further , the results suggest significant improvements in parental satisfaction and conflict about parenting as well as a sleeper effect for parental efficacy . The results indicate that Stepping Stones Triple P is a promising intervention for parents of children with ASD . Limitations and future research are also addressed OBJECTIVES The aim was to examine functional outcomes following traumatic brain injury ( TBI ) during early childhood , to investigate impairments up to 5 years postinjury and identify predictors of outcome . METHODS The study compared three groups of children ( mild = 11 , moderate = 22 , severe = 15 ) , aged 2.0 - 6.11 years at injury , to a healthy control group ( n = 17 ) . Using a prospect i ve , longitudinal design , adaptive abilities , behavior , and family functioning were investigated acutely , 6 , 30 months and 5 years postinjury , with educational progress investigated at 30 months and 5 years postinjury . RESULTS A strong association was suggested between injury severity and outcomes across all domains . Further , 5-year outcomes in adaptive and behavioral domains were best predicted by preinjury levels of child function , and educational performance by injury severity . CONCLUSION Children who sustain a severe TBI in early childhood are at greatest risk of long-term impairment in day-to-day skills in the long-term postinjury |
12,436 | 24,887,111 | Discussion We anticipate that this review will highlight how men and women differ in methadone treatment outcomes and allow us to generate conclusions that can be applied to treatment in a clinical setting . | Background Use of methadone for the treatment of opioid addiction is an effective harm-reduction approach , although variability in treatment outcomes among individuals has been reported .
Men and women with opioid addiction have been known to differ in factors such as opioid use patterns and characteristics at treatment entry ; however , little has been reported about differences in methadone treatment outcomes between men and women .
Therefore , we present a protocol for a systematic review which aims to provide a summary of existing literature on sex differences in outcomes of methadone treatment for opioid addiction . | Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Few clinical trials include sex as a factor . This analysis explored within-sex differences in response to opioid agonist medications . Males and females r and omly assigned to buprenorphine , LAAM , or methadone were compared on opioid use and retention in treatment . Females receiving buprenorphine had less objective drug use than females receiving methadone , while males receiving LAAM had less objective drug use than males receiving buprenorphine . Retention in treatment was longer for both sexes receiving methadone versus LAAM . Within-subject change results indicate that all three medications benefit both sexes . Clinical trials should be design ed to examine the impact of sex on outcomes BACKGROUND Genetic variations of the dopamine and opioid receptors could influence the response to methadone maintenance treatment ( MMT ) . METHODS We included 238 MMT patients according to their response to treatment and methadone dosing , along with 217 subjects without substance dependence . All were genotyped for polymorphisms of the dopamine D1 , D2 , micro-opioid and delta-opioid receptor genes . RESULTS The polymorphisms of the micro-opioid ( 118A > G ) , delta-opioid ( 921T > C ) , dopamine D1 ( DdeI ) and D2 ( TaqI A ) receptor genes were not associated with response to MMT and methadone dosing , whereas an association was found with the dopamine D2 receptor ( DRD2 ) 957C > T polymorphism . The 957CC carriers were more frequently non-responders to treatment ( OR=2.4 ; p=0.02 ) and presented a fourfold shorter period of negative urine screening ( p=0.02 ) . No significant differences in allele frequencies were observed between the MMT patients and the control group , suggesting no association of the analyzed polymorphisms with opioid dependence . CONCLUSIONS These results suggest that DRD2 genotype may contribute to the underst and ing of the interindividual variability to the response to MMT OBJECTIVE Women represent the largest percentage of new HIV infections globally . Yet , no large-scale studies have examined the experience of pain and its treatment in women living with HIV . DESIGN This study used structural equation modeling to examine sex differences in pain and the use and misuse of prescription analgesics in a representative sample of HIV+ persons in the United Stated within a prospect i ve , longitudinal design . OUTCOME MEASURES Bodily pain subscale of the Short-Form 36 and Modified Short Form of the World Health Organization 's Composite International Diagnostic Interview ( opioid misuse ) . RESULTS Women reported more pain than men over a roughly 6-month period regardless of mode of HIV transmission or prior drug use history . Men acknowledged more misuse of prescription analgesics over an approximate 1-year period compared with women , after taking into account pain , use of analgesics specifically for pain , and drug use history . Weaker associations between pain and use of analgesics specifically for pain that persisted over time were found among women compared with men . For both men and women , pain was stable over time . Problem drug use history exerted significant direct and indirect effects on pain , opioid misuse , and pain-specific analgesic use across sex . CONCLUSION The current findings are consistent with prior evidence indicating female pain predominance as well as the undertreatment of pain among women with HIV . Efforts should be made to improve the assessment and long-term management of pain in HIV+ persons INTRODUCTION We conducted a follow-up study to evaluate the outcome of a heroin-dependent population 25 years after their first enrollment in methadone maintenance treatment ( MMT ) . We assessed mortality in the sample plus actual drug use , treatment , and medical factors associated with drug dependence , focusing on possible gender differences . METHODS Prospect i ve follow-up study of 214 heroin-dependent patients consecutively admitted for MMT between 1980 and 1984 in the Asturias Public Health Service . The st and ardized mortality ratio ( SMR ) and 95 % confidence interval ( CI ) were calculated . An ad-hoc protocol on drug misuse and treatment , drug-related morbidity and Clinical Global Impression ( CGI ) scores were assessed in the survivors ' sample . RESULTS Information was received on 159 subjects , 106 of whom were deceased . Men accounted for 76.2 % of the study cohort . Over the 25-year follow-up period , the SMR was 22.51 ( 95 % CI=22.37 - 22.64 ) . In the survivors sample , 39.6 % were still enrolled in MMT ; human immunodeficiency virus ( HIV ) was diagnosed in 47.2 % and hepatitis B/C in 81.1 % ; current heroin use was reported by 22.6 % . There were no gender differences in mortality or HIV and hepatitis B/C status . None of the female survivors were using heroin at the 25-year follow-up compared with 31.1 % of males . CONCLUSIONS This study confirms the high mortality of heroin addicts even after enrollment in MMT . Severity of the addiction in terms of mortality was similar in both genders . Women who survived the 25-year follow-up were more likely to have stopped using heroin than men Abstract We prospect ively compared gender outcome among 470 MMT patients admitted between June 1993 and Dec 2002 . Urine sample s were analyzed for drug abuse after one month and after one year . On admission females 131(27.9 % ) were significantly younger ( 34.5 ± 7.5 years ) than males 339(72.1 % ) ( 37.3 ± 8.3 years ) ( ANOVA;F = 11 , p = 0.001 ) and had significantly higher cocaine abuse ( 20 % vs. 11.3 % ) ( Fisher 's Exact Test , p = 0.02 ) . After one year , groups had : ( a ) similar retention in treatment ( 76.3%-females , 72.6%-males ) , ( b ) stop in opiate abuse ( 65%-females , 65.3%-males ) , ( c ) a net decrease in cocaine abuse ( % positive that became negative minus % negative that became positive ) ( 68.0%-females , 51.6%-males ) . Females who were admitted to treatment while pregnant ( n = 45 ) were significantly younger ( 31.5 ± 5.4 years ) compared to 86 non-pregnant ( 36.1 ± 7.9 , ANOVA F = 12.1 , p = 0.001 ) . We concluded that compared to males , females started MMT younger and had a higher proportion of cocaine abuse even though females ' outcome were similar to males ' |
12,437 | 28,438,770 | When exercise prescription was examined , a duration of 45–60 min per session and at least moderate intensity , were associated with benefits to cognition .
Conclusions Physical exercise improved cognitive function in the over 50s , regardless of the cognitive status of participants . | Background Physical exercise is seen as a promising intervention to prevent or delay cognitive decline in individuals aged 50 years and older , yet the evidence from review s is not conclusive .
Objectives To determine if physical exercise is effective in improving cognitive function in this population . | BACKGROUND Few scientific studies have examined movement-based embodied contemplative practice s such as yoga and their effects on cognition . The purpose of this r and omized controlled trial was to examine the effects of an 8-week Hatha yoga intervention on executive function measures of task switching and working memory capacity . METHODS Community-dwelling older adults ( N = 118 ; mean age = 62.0 ) were r and omized to one of two groups : a Hatha yoga intervention or a stretching-strengthening control . Both groups participated in hour-long exercise classes 3 × /week over the 8-week study period . All participants completed established tests of executive function including the task switching paradigm , n-back and running memory span at baseline and follow-up . RESULTS Analysis of covariances showed significantly shorter reaction times on the mixed and repeat task switching trials ( partial η(2 ) = .04 , p < .05 ) for the Hatha yoga group . Higher accuracy was recorded on the single trials ( partial η(2 ) = .05 , p < .05 ) , the 2-back condition of the n-back ( partial η(2 ) = .08 , p < .001 ) , and partial recall scores ( partial η(2 ) = .06 , p < .01 ) of running span task . CONCLUSIONS Following 8 weeks of yoga practice , participants in the yoga intervention group showed significantly improved performance on the executive function measures of working memory capacity and efficiency of mental set shifting and flexibility compared with their stretching-strengthening counterparts . Although the underlying mechanisms need to be investigated , these results dem and larger systematic trials to thoroughly examine effects of yoga on executive function as well as across other domains of cognition , and its potential to maintain or improve cognitive functioning in the aging process OBJECTIVE We evaluated the effects of exercise on neurobehavioral function in healthy older people more than 75 years of age . DESIGN A r and omized controlled trial with 6-month follow-up was conducted . SETTING The study was performed in the rural town of Kahoku , Japan , the population of which is considered representative of the older population of Japan . PARTICIPANTS We studied 42 healthy volunteers ( 18 men and 24 women ; mean age , 79 years ( range 75 to 87 years ) ) who were r and omly assigned to one of two groups , exercise or control . INTERVENTION Subjects assigned to the exercise group were instructed to exercise for 60 minutes twice a week for 6 months . Subjects in the control group were not instructed to engage in an specific exercise regimen . MEASUREMENTS The following measurements were recorded for both groups at baseline and at 6-month follow-up : ( 1 ) Neurobehavioral function as determined by the following tests : Mini-Mental State Exam ( MMSE ) , Hasegawa Dementia Scale Revised ( HDSR ) , Visuospatial Cognitive Performance Test ( VCP-test ) , Button score , Up & Go test , and Functional Reach ; and ( 2 ) Body mass index and blood pressure . RESULTS The effects of exercise were shown in the Up & Go test , and Functional Reach ( ANOVA with repeated measures ) . CONCLUSION This study demonstrates the acceptability and effectiveness of exercise on neurobehavioral function , even in older people more than 75 years of age Physical exercise has been shown to increase brain volume and improve cognition in r and omized trials of non-demented elderly . Although greater social engagement was found to reduce dementia risk in observational studies , r and omized trials of social interventions have not been reported . A representative sample of 120 elderly from Shanghai , China was r and omized to four groups ( Tai Chi , Walking , Social Interaction , No Intervention ) for 40 weeks . Two MRIs were obtained , one before the intervention period , the other after . A neuropsychological battery was administered at baseline , 20 weeks , and 40 weeks . Comparison of changes in brain volumes in intervention groups with the No Intervention group were assessed by t-tests . Time-intervention group interactions for neuropsychological measures were evaluated with repeated- measures mixed models . Compared to the No Intervention group , significant increases in brain volume were seen in the Tai Chi and Social Intervention groups ( p < 0.05 ) . Improvements also were observed in several neuropsychological measures in the Tai Chi group , including the Mattis Dementia Rating Scale score ( p = 0.004 ) , the Trailmaking Test A ( p = 0.002 ) and B ( p = 0.0002 ) , the Auditory Verbal Learning Test ( p = 0.009 ) , and verbal fluency for animals ( p = 0.01 ) . The Social Interaction group showed improvement on some , but fewer neuropsychological indices . No differences were observed between the Walking and No Intervention groups . The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise ( Tai Chi ) . In addition , intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements Background Mild cognitive impairment ( MCI ) is a well-recognised risk factor for dementia and represents a vital opportunity for intervening . Exercise is a promising strategy for combating cognitive decline by improving brain structure and function . Specifically , aerobic training ( AT ) improved spatial memory and hippocampal volume in healthy community-dwelling older adults . In older women with probable MCI , we previously demonstrated that resistance training ( RT ) and AT improved memory . In this secondary analysis , we investigated : ( 1 ) the effect of RT and AT on hippocampal volume and ( 2 ) the association between change in hippocampal volume and change in memory . Methods 86 women aged 70–80 years with probable MCI were r and omly assigned to a 6-month , twice-weekly programme of : ( 1 ) AT , ( 2 ) RT or ( 3 ) balance and tone training ( BAT ; ie , control ) . At baseline and trial completion , participants performed a 3 T MRI scan to determine hippocampal volume . Verbal memory and learning were assessed by Rey 's Auditory Verbal Learning Test . Results Compared with the BAT group , AT significantly improved left , right and total hippocampal volumes ( p≤0.03 ) . After accounting for baseline cognitive function and experimental group , increased left hippocampal volume was independently associated with reduced verbal memory and learning performance as indexed by loss after interference ( r=0.42 , p=0.03 ) . Conclusions Aerobic training significantly increased hippocampal volume in older women with probable MCI . More research is needed to ascertain the relevance of exercise-induced changes in hippocampal volume on memory performance in older adults with MCI . Trail registration number NCT00958867 This study aim ed to investigate the effects of a long-term resistance exercise intervention on executive functions in healthy elderly males , and to further underst and the potential neurophysiological mechanisms mediating the changes . The study assessed forty-eight healthy elderly males r and omly assigned to exercise ( n = 24 ) or control ( n = 24 ) groups . The assessment included neuropsychological and neuroelectric measures during a variant of the oddball task paradigm , as well as growth hormone ( GH ) , insulin-like growth factor-1 ( IGF-1 ) , and homocysteine levels at baseline and after either a 12 month intervention of resistance exercise training or control period . The results showed that the control group had a significantly lower accuracy rate and smaller P3a and P3b amplitudes in the oddball condition after 12 months . The exercise group exhibited improved reaction times ( RTs ) , sustained P3a and P3b amplitudes , increased levels of serum IGF-1 , and decreased levels of serum homocysteine . The changes in IGF-1 levels were significantly correlated with the changes in RT and P3b amplitude of the oddball condition in the exercise group . In conclusion , significantly enhanced serum IGF-1 levels after 12 months of resistance exercise were inversely correlated with neurocognitive decline in the elderly . These findings suggest that regular resistance exercise might be a promising strategy to attenuate the trajectory of cognitive aging in healthy elderly individuals , possibly mediated by IGF-1 BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions Strength training has been reported as a potentially useful exercise to improve psychological aspects in the elderly , but its effects remain controversial . This study investigated the effectiveness of strength training conducted twice a week for 12 weeks for improving health-related quality of life ( HRQOL ) and executive cognitive function . The study was a single-blind r and omized controlled trial with assessment s before and after intervention . HRQOL and executive function were assessed using the SF-36 Health Status Survey and a computerized neuro-cognitive assessment using task-switch reaction time trials , respectively . Subjects comprised 119 participants > or = 65 years old , r and omized to either strength training ( n=65 ) or health education classes ( controls , n=54 ) . The strength training program was design ed to strengthen the large muscle groups most important for functional activities and to improve balance . The effects of the intervention on the eight dimensions of the SF-36 in the control and training groups were analyzed . Only the mental health scale of the SF-36 was significantly improved for the training group compared with controls after 12 weeks . Task-switch reaction time and correct response rate remained unchanged . Short-term strength training might have modest positive effects on HRQOL , although this training period may not be sufficient to affect executive function in relatively healthy older people The aim of this study was to investigate the effects of a 6-month exercise program on cognitive function and blood viscosity in sedentary elderly men . Forty-six healthy inactive men , aged 60–75 years were r and omly distributed into a control group ( n=23 ) and an experimental group ( n=23 ) . Participants underwent blood analysis and physical and memory evaluation , before and after the 6-month program of physical exercise . The control group was instructed not to alter its everyday activities ; the experimental group took part in the fitness program . The program was conducted using a cycle ergometer , 3 times per week on alternate days , with intensity and volume individualized at ventilatory threshold 1 . Sessions were continuous and maximum duration was 60 min each . There was significant improvement in memory ( 21 % ; P<0.05 ) , decreased blood viscosity ( −19 % ; P<0.05 ) , and higher aerobic capacity ( 48 % ; P<0.05 ) among participants in the experimental group compared with the control group . These data suggest that taking part in an aerobic physical fitness program at an intensity corresponding to ventilatory threshold-1 may be considered a nonmedication alternative to improve physical and cognitive function The aims of this study were to examine the effects of aerobic exercise on measures of executive performance and their relationships with changes in cardiorespiratory fitness , cardiac vagal control ( heart rate variability ) and psychological variables . Thirty-six sedentary seniors aged 60 - 75 years were r and omly assigned to a swimming and aquaerobics program or a stretching program two times a week for 21 weeks . Executive functions ( inhibition , updating of working memory and cognitive flexibility ) and cardiorespiratory fitness ( estimated VO2max ) were assessed at the start , after 10 weeks of program and at the end of the program . Resting HRV and measures of psychological outcomes ( depression , self-efficacy , decisional balance ) were obtained at the start and at the end of the program . Participants of both groups significantly improved their VO2max level , their psychological state and their performance for the 2-back task . Only the participants in the aquaerobics group significantly improved their vagally-mediated HRV and their performance for the Stroop test and the verbal running-span test at the end of the program . Only improvements in cardiac vagal control and in inhibition were shown to be functionally related . These results are discussed in line with the model of neurovisceral integration CONTEXT Evidence suggests that physical activity may be related to the clinical expression of dementia . Whether the association includes low-intensity activity such as walking is not known . OBJECTIVE To examine the association between walking and future risk of dementia in older men . DESIGN Prospect i ve cohort study . SETTING AND PARTICIPANTS Distance walked per day was assessed from 1991 to 1993 in 2257 physically capable men aged 71 to 93 years in the Honolulu-Asia Aging Study . Follow-up for incident dementia was based on neurological assessment at 2 repeat examinations ( 1994 - 1996 and 1997 - 1999 ) . MAIN OUTCOME MEASURES Overall dementia , Alzheimer disease , and vascular dementia . RESULTS During the course of follow-up , 158 cases of dementia were identified ( 15.6/1000 person-years ) . After adjusting for age , men who walked the least ( < 0.25 mile/d ) experienced a 1.8-fold excess risk of dementia compared with those who walked more than 2 mile/d ( 17.8 vs 10.3/1000 person-years ; relative hazard [ RH ] , 1.77 ; 95 % confidence interval [ CI ] , 1.04 - 3.01 ) . Compared with men who walked the most ( > 2 mile/d ) , an excess risk of dementia was also observed in those who walked 0.25 to 1 mile/d ( 17.6 vs 10.3/1000 person-years ; RH , 1.71 ; 95 % CI , 1.02 - 2.86 ) . These associations persisted after accounting for other factors , including the possibility that limited amounts of walking could be the result of a decline in physical function due to pre clinical dementia . CONCLUSIONS Findings suggest that walking is associated with a reduced risk of dementia . Promoting active lifestyles in physically capable men could help late-life cognitive function BACKGROUND Cognitive decline among seniors is a pressing health care issue . Specific exercise training may combat cognitive decline . We compared the effect of once-weekly and twice-weekly resistance training with that of twice-weekly balance and tone exercise training on the performance of executive cognitive functions in senior women . METHODS In this single-blinded r and omized trial , 155 community-dwelling women aged 65 to 75 years living in Vancouver were r and omly allocated to once-weekly ( n = 54 ) or twice-weekly ( n = 52 ) resistance training or twice-weekly balance and tone training ( control group ) ( n = 49 ) . The primary outcome measure was performance on the Stroop test , an executive cognitive test of selective attention and conflict resolution . Secondary outcomes of executive cognitive functions included set shifting as measured by the Trail Making Tests ( parts A and B ) and working memory as assessed by verbal digit span forward and backward tests . Gait speed , muscular function , and whole-brain volume were also secondary outcome measures . RESULTS Both resistance training groups significantly improved their performance on the Stroop test compared with those in the balance and tone group ( P < or = .03 ) . Task performance improved by 12.6 % and 10.9 % in the once-weekly and twice-weekly resistance training groups , respectively ; it deteriorated by 0.5 % in the balance and tone group . Enhanced selective attention and conflict resolution was significantly associated with increased gait speed . Both resistance training groups demonstrated reductions in whole-brain volume compared with the balance and tone group at the end of the study ( P < or = .03 ) . CONCLUSION Twelve months of once-weekly or twice-weekly resistance training benefited the executive cognitive function of selective attention and conflict resolution among senior women . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00426881 Abstract : A r and omised controlled trial was conducted to determine whether a 12–month program of group exercise had beneficial effects on physiological and cognitive functioning and mood in 187 older community – dwelling women . The exercisers ( n= 94 ) and controls ( n= 93 ) were well matched in terms of the test measures and a number of health and life – style assessment s. The mean number of classes attended by the 71 exercise subjects who completed the program was 59.0 ( range 26 to 82 ) . At the end of the trial , the exercisers showed significant improvements in reaction time , strength , memory span and measures of wellbeing when compared with the controls . There was also an indication that anxiety had been reduced in the exercisers . Within the exercise group , improvements in memory span were associated with concomitant improvements in both reaction time and muscle strength . Also , within this group , initial mood measures were significantly inversely associated with improvements at retest , which suggests that the program may have normalised mood states in subjects who had high initial depression , anxiety and stress levels , rather than inducing improvements in all subjects . These findings suggest that group exercise has beneficial effects on physiological and cognitive functioning and wellbeing in older people PURPOSE The purpose of this study was to assess the impact of 24 wk of resistance training at two different intensities on cognitive functions in the elderly . METHODS Sixty-two elderly individuals were r and omly assigned to three groups : CONTROL ( N = 23 ) , experimental moderate ( EMODERATE ; N = 19 ) , and experimental high ( EHIGH ; N = 20 ) . The volunteers were assessed on physical , hemodynamic , cognitive , and mood parameters before and after the program . RESULTS On the 1 RM test ( P < 0.001 ) , the two experimental groups performed better than the CONTROL group , but they did not show differences between themselves . The EHIGH group gained more lean mass ( P = 0.05 ) than the CONTROL group and performed better on the following tests : digit span forward ( P < 0.001 ) , Corsi 's block-tapping task backward ( P = 0.001 ) , similarities ( P = 0.03 ) , Rey-Osterrieth complex figure immediate recall ( P = 0.02 ) , Toulouse-Pieron concentration test errors ( P = 0.01 ) , SF-36 ( general health ) ( P = 0.04 ) , POMS ( tension-anxiety , P = 0.04 ; depression-dejection , P = 0.03 ; and total mood disorder , P = 0.03 ) . The EMODERATE group scored higher means than the CONTROL group on digit span forward ( P < 0.001 ) , Corsi 's block-tapping task backward ( P = 0.01 ) , similarities ( P = 0.02 ) , Rey-Osterrieth complex figure immediate recall ( P = 0.02 ) , SF-36 ( general health , P = 0.005 ; vitality , P = 0.006 ) , POMS ( tension-anxiety , P = 0.001 ; depression-dejection , P = 0.006 ; anger-hostility , P = 0.006 ; fatigue-inertia , P = 0.02 ; confusion-bewilderment , P = 0.02 ; and total mood disorder , P = 0.001 ) . We also found that IGF-1 serum levels were higher in the experimental groups ( EMODERATE , P = 0.02 ; EHIGH , P < 0.001 ) . CONCLUSIONS Moderate- and high-intensity resistance exercise programs had equally beneficial effects on cognitive functioning We have compared the effects of different 12-week exercise programs on simple and choice reaction and movement times in persons 61 to 84 years old . One hundred thirty-eight volunteers were r and omized to either a control group , a two-day exercise group ( two 60-min sessions a week of aerobic exercises ) , or a two-day physical plus cognitive exercise group ( two 60-min sessions a week of aerobic and cognitive exercises ) . At follow-up , the aerobic and cognitive exercise program was found to have result ed in significant positive effects . Improvements were found in the two-day physical plus cognitive exercise group in all of the reaction parameters , particularly improvement in choice reaction time , which is used in most daily activities . Our results suggest that to improve reaction time values , it is advisable to include cognitive features into a physical exercise routine The hippocampus shrinks in late adulthood , leading to impaired memory and increased risk for dementia . Hippocampal and medial temporal lobe volumes are larger in higher-fit adults , and physical activity training increases hippocampal perfusion , but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown . Here we show , in a r and omized controlled trial with 120 older adults , that aerobic exercise training increases the size of the anterior hippocampus , leading to improvements in spatial memory . Exercise training increased hippocampal volume by 2 % , effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF , a mediator of neurogenesis in the dentate gyrus . Hippocampal volume declined in the control group , but higher preintervention fitness partially attenuated the decline , suggesting that fitness protects against volume loss . Cau date nucleus and thalamus volumes were unaffected by the intervention . These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood , which is accompanied by improved memory function Cardiovascular fitness is thought to offset declines in cognitive performance , but little is known about the cortical mechanisms that underlie these changes in humans . Research using animal models shows that aerobic training increases cortical capillary supplies , the number of synaptic connections , and the development of new neurons . The end result is a brain that is more efficient , plastic , and adaptive , which translates into better performance in aging animals . Here , in two separate experiments , we demonstrate for the first time to our knowledge , in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task . Specifically , highly fit ( Study 1 ) or aerobically trained ( Study 2 ) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning , when compared with low-fit ( Study 1 ) or nonaerobic control ( Study 2 ) participants . Additionally , in both studies there exist groupwise differences in activation of the anterior cingulate cortex , which is thought to monitor for conflict in the attentional system , and signal the need for adaptation in the attentional network . These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain , and may serve to reduce both biological and cognitive senescence in humans OBJECTIVES Frailty is a state of vulnerability associated with increased risks of fall , hospitalization , cognitive deficits , and psychological distress . Studies with healthy senior suggest that physical exercise can help improve cognition and quality of life . Whether frail older adults can show such benefits remains to be documented . METHOD A total of 83 participants aged 61 - 89 years were assigned to an exercise-training group ( 3 times a week for 12 weeks ) or a control group ( waiting list ) . Frailty was determined by a complete geriatric examination using specific criteria . Pre- and post-test measures assessed physical capacity , cognitive performance , and quality of life . RESULTS Compared with controls , the intervention group showed significant improvement in physical capacity ( functional capacities and physical endurance ) , cognitive performance ( executive functions , processing speed , and working memory ) , and quality of life ( global quality of life , leisure activities , physical capacity , social/family relationships , and physical health ) . Benefits were overall equivalent between frail and nonfrail participants . DISCUSSION Physical exercise training leads to improved cognitive functioning and psychological well-being in frail older adults BACKGROUND Several reports suggest beneficial impacts of either physical or mental activity on cognitive function in old age . However , the differential effects of complex mental and physical activities on cognitive performance in humans remain to be clarified . METHODS This r and omized controlled trial evaluates a cognitive and a physical st and ardized 6-month activity intervention ( 3 x 1.5 h/wk ) conducted in Berlin ( Germany ) . Two hundred fifty nine healthy women aged 70 - 93 years were r and omized to a computer course ( n = 92 ) , an exercise course ( n = 91 ) , or a control group ( n = 76 ) , of whom 230 completed the 6-month assessment . Group differences in change over a period of 6 months in episodic memory ( story recall , possible range , 0 - 21 ; word recall , possible range , 0 - 16 ) , executive control ( working memory , ie , time quotient of Trail Making Tests B/A ) , and verbal fluency were evaluated by analyses of covariance ( intention to treat ) adjusting for baseline , fluid intelligence , and educational level . RESULTS In contrast to the control group , both the exercise group , DeltaM ( SD ) = 2.09 ( 2.66 ) , p < .001 , and the computer group , DeltaM ( SD ) = 1.89 ( 2.88 ) , p < .001 , showed improved delayed story recall . They maintained performance in delayed word recall and working memory ( time measure ) as opposed to the control group that showed a decline , DeltaM ( SD ) = -0.91 ( 2.15 ) , p = .001 , and DeltaM ( SD ) = 0.24 ( 0.68 ) , p = .04 , respectively . CONCLUSIONS In healthy older women , participation in new stimulating activities contributes to cognitive fitness and might delay cognitive decline . Exercise and computer classes seem to generate equivalent beneficial effects Objective To evaluate the effects of Tai chi exercise on balance , sleep quality , and cognitive performance in community-dwelling elderly in Vinh city , Vietnam . Design A r and omized controlled trial . Participants One hundred two subjects were recruited . Intervention Subjects were divided r and omly into two groups . The Tai chi group was assigned 6 months ’ Tai chi training . The control group was instructed to maintain their routine daily activities . Outcome measures The Falls Efficacy Scale ( FES ) , Pittsburgh Sleep Quality Index ( PSQI ) , and Trail Making Test ( TMT ) were used as primary outcome measures . Results Participants in the Tai chi group reported significant improvement in TMT ( part A ) ( F [ 1 , 71 ] = 78.37 , P < 0.001 ) and in TMT ( part B ) , ( F [ 1 , 71 ] = 175.00 , P < 0.001 ) in comparison with the control group . Tai chi participants also reported better scores in FES ( F [ 1 , 71 ] = 96.90 , P < 0.001 ) and in PSQI ( F [ 1,71 ] = 43.69 , P = 0.001 ) than the control group . Conclusion Tai chi is beneficial to improve balance , sleep quality , and cognitive performance of the elderly This study examined the effects of a 12-week aerobic exercise program on psychological well-being and cognitive functioning in a group of ethnically diverse older adults living in an urban community . Forty-eight older men and women ( mean age = 72 + /- 6 ) were r and omly assigned to one of three groups : an aerobic exercise training group , a social activity control group , or a waiting list group . Results indicated little change in psychological well-being and provided limited support for the association of physiological improvement with enhanced mastery and cognitive functioning This study examined the effects of two short physical training programs on various parameters of heart rate variability ( HRV ) and on executive performance in older people . Twenty-four sedentary men and women aged 65–78 years were r and omly assigned to an aerobic exercise program or a stretching program three times a week for 12 weeks . Resting HRV was measured in time and frequency domains in each participant before and after the 12-week programs . Executive performance was measured with the Wisconsin card sorting test ( WCST ) . Significant group – session interactions emerged for the st and ard deviation of normal beat-to-beat ( R – R ) intervals , the root-mean-square of successive R – R , and high frequency power . Only the aerobic training group increased vagal-mediated HRV parameters . Moreover , only the participants in the aerobic training group improved their performance on the WCST . These results highlight the role of aerobic exercise as an important cardiac and brain protective factor , and suggest a direct link between exercise , HRV , and cognition in the aged population BACKGROUND Physical and cognitive activity seems to be an effective strategy by which to promote age-sensitive fluid cognitive abilities in older adults . METHOD In this r and omized controlled trial , 70 healthy senior citizens ( age 60 - 75 ) were allocated to a physical , cognitive , combined physical plus cognitive , and waiting control group . The trial assessed information processing speed , short-term memory , spatial relations , concentration , reasoning , and cognitive speed . RESULTS In contrast to the control group , the physical , cognitive , and combined training groups enhanced their concentration immediately after intervention . Only the physical training group showed improved concentration 3 months later . The combined training group displayed improved cognitive speed both immediately and three months after intervention . The cognitive training group displayed improved cognitive speed 3 months after intervention . CONCLUSIONS Physical , cognitive , and combined physical plus cognitive activity can be seen as cognition-enrichment behaviors in healthy older adults that show different rather than equal intervention effects CONTEXT Because Tai Chi ( TC ) is beneficial to elders without cognitive impairment ( CI ) , it also may benefit elders with CI . But elders with CI have generally been excluded from TC studies because many measurement tools require verbal reports that some elders with CI are unable to provide . OBJECTIVES To test the efficacy of a TC program in improving pain and other health outcomes in community-dwelling elders with knee osteoarthritis ( OA ) and CI . METHODS This pilot cluster-r and omized trial was conducted between January 2008 and June 2010 ( Clinical Trials.gov Identifier : NCT01528566 ) . The TC group attended Sun style TC classes , three sessions a week for 20 weeks ; the control group attended classes providing health and cultural information for the same length of time . Measures included the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain , physical function and stiffness subscales ; the Get Up and Go test ; the Sit-to-St and test ; and the Mini-Mental State Examination ( MMSE ) , administered at baseline , every four weeks during the intervention and at the end of the study ( post-test ) . RESULTS Eight sites participated in either the TC group ( four sites , 28 participants ) or control group ( four sites , 27 participants ) . The WOMAC pain ( P = 0.006 ) and stiffness scores ( P = 0.010 ) differed significantly between the two groups at post-test , whereas differences between the two groups in the WOMAC physical function score ( P = 0.071 ) and the MMSE ( P = 0.096 ) showed borderline significance at the post-test . WOMAC pain ( P = 0.001 ) , physical function ( P = 0.021 ) , and stiffness ( P ≤ 0.001 ) scores improved significantly more over time in the TC group than in controls . No adverse events were found in either group . CONCLUSION Practicing TC can be efficacious in reducing pain and stiffness in elders with knee OA and CI BACKGROUND Mild cognitive impairment ( MCI ) increases dementia risk with no pharmacologic treatment available . METHODS The Study of Mental and Resistance Training was a r and omized , double-blind , double-sham controlled trial of adults with MCI . Participants were r and omized to 2 supervised interventions : active or sham physical training ( high intensity progressive resistance training vs seated calisthenics ) plus active or sham cognitive training ( computerized , multidomain cognitive training vs watching videos/quizzes ) , 2 - 3 days/week for 6 months with 18-month follow-up . Primary outcomes were global cognitive function ( Alzheimer 's Disease Assessment Scale-cognitive subscale ; ADAS-Cog ) and functional independence ( Bayer Activities of Daily Living ) . Secondary outcomes included executive function , memory , and speed/attention tests , and cognitive domain scores . RESULTS One hundred adults with MCI [ 70.1 ( 6.7 ) years ; 68 % women ] were enrolled and analyzed . Resistance training significantly improved the primary outcome ADAS-Cog ; [ relative effect size ( 95 % confidence interval ) -0.33 ( -0.73 , 0.06 ) ; P < .05 ] at 6 months and executive function ( Wechsler Adult Intelligence Scale Matrices ; P = .016 ) across 18 months . Normal ADAS-Cog scores occurred in 48 % ( 24/49 ) after resistance training vs 27 % ( 14/51 ) without resistance training [ P < .03 ; odds ratio ( 95 % confidence interval ) 3.50 ( 1.18 , 10.48 ) ] . Cognitive training only attenuated decline in Memory Domain at 6 months ( P < .02 ) . Resistance training 18-month benefit was 74 % higher ( P = .02 ) for Executive Domain compared with combined training [ z-score change = 0.42 ( 0.22 , 0.63 ) resistance training vs 0.11 ( -0.60 , 0.28 ) combined ] and 48 % higher ( P < .04 ) for Global Domain [ z-score change = .0.45 ( 0.29 , 0.61 ) resistance training vs 0.23 ( 0.10 , 0.36 ) combined ] . CONCLUSIONS Resistance training significantly improved global cognitive function , with maintenance of executive and global benefits over 18 months IMPORTANCE The prevalence of cognitive impairment and dementia are projected to rise dramatically during the next 40 years , and strategies for maintaining cognitive function with age are critically needed . Physical or mental activity alone result in relatively small , domain-specific improvements in cognitive function in older adults ; combined interventions may have more global effects . OBJECTIVE To examine the combined effects of physical plus mental activity on cognitive function in older adults . DESIGN R and omized controlled trial with a factorial design . SETTING San Francisco , California . PARTICIPANTS A total of 126 inactive , community-residing older adults with cognitive complaints . INTERVENTIONS All participants engaged in home-based mental activity ( 1 h/d , 3 d/wk ) plus class-based physical activity ( 1 h/d , 3 d/wk ) for 12 weeks and were r and omized to either mental activity intervention ( MA-I ; intensive computer ) or mental activity control ( MA-C ; educational DVDs ) plus exercise intervention ( EX-I ; aerobic ) or exercise control ( EX-C ; stretching and toning ) ; a 2 × 2 factorial design was used so that there were 4 groups : MA-I/EX-I , MA-I/EX-C , MA-C/EX-1 , and MA-C/EX-C. MAIN OUTCOME MEASURES Global cognitive change based on a comprehensive neuropsychological test battery . RESULTS Participants had a mean age of 73.4 years ; 62.7 % were women , and 34.9 % were Hispanic or nonwhite . There were no significant differences between the groups at baseline . Global cognitive scores improved significantly over time ( mean , 0.16 SD ; P < .001 ) but did not differ between groups in the comparison between MA-I and MA-C ( ignoring exercise , P = .17 ) , the comparison between EX-I and EX-C ( ignoring mental activity , P = .74 ) , or across all 4 r and omization groups ( P = .26 ) . CONCLUSIONS AND RELEVANCE In inactive older adults with cognitive complaints , 12 weeks of physical plus mental activity was associated with significant improvements in global cognitive function with no evidence of difference between intervention and active control groups . These findings may reflect practice effects or may suggest that the amount of activity is more important than the type in this subject population . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00522899 The cardiovascular and behavioral adaptations associated with a 4-month program of aerobic exercise training were examined in 101 older men and women ( mean age = 67 years ) . Subjects were r and omly assigned to an Aerobic Exercise group , a Yoga and Flexibility control group , or a Waiting List control group . Prior to and following the 4-month program , subjects underwent comprehensive physiological and psychological evaluations . Physiological measures included measurement of blood pressure , lipids , bone density , and cardiorespiratory fitness including direct measurements of peak oxygen consumption ( VO2 ) and anaerobic threshold . Psychological measures included measures of mood , psychiatric symptoms , and neuropsychological functioning . This study demonstrated that 4 months of aerobic exercise training produced an overall 11.6 % improvement in peak VO2 and a 13 % increase in anaerobic threshold . In contrast , the Yoga and Waiting List control groups experienced no change in cardiorespiratory fitness . Other favorable physiological changes observed among aerobic exercise participants included lower cholesterol levels , diastolic blood pressure levels , and for subjects at risk for bone fracture , a trend toward an increase in bone mineral content . Although few significant psychological changes could be attributed to aerobic exercise training , participants in the two active treatment groups perceived themselves as improving on a number of psychological and behavioral dimensions OBJECTIVE To evaluate the effects of endurance exercise training ( EET ) on the cognitive status of healthy community-dwelling older adults . METHODS A r and omized controlled trial was conducted involving community-dwelling older adults from the town of Pianoro ( northern Italy ) . We r and omized 120 healthy subjects aged 65 - 74 years , both genders , to treatment ( N = 60 ) and control ( N = 60 ) groups . The treatment consisted of 12 months of supervised EET in a community gym , 3 h a week . All participants were assessed both at baseline and after 12 months on an intention-to-treat analysis . Cognitive status was assessed by one single test ( Mini Mental State Examination , MMSE ) . Anthropometric indexes , routine laboratory measurements and C-reactive protein ( CRP ) were also assessed . RESULTS The control group showed a significant decrease in MMSE score ( mean difference -1.21 , 95 % CI -1.83/-0.60 , p = 0.0002 ) , which differed significantly ( p = 0.02 ) from the treatment group scores ( -0.21 , 95 % CI -0.79/0.37 , p = 0.47 ) . The odds ratio for the treated older adults to have a stable cognitive status after 1 year , as compared to the control group , was 2.74 ( 95 % CI 1.16/6.48 ) after adjustment for age , gender , educational level and several other possible confounders . Blood pressure , body mass index , waist circumference and serum cholesterol did not differ significantly between the two groups , while CRP decreased only in the treatment group . CONCLUSIONS A 12-month EET intervention may reduce the progression of age-related cognitive decline in healthy older adults Previous studies concerning psychological benefits of exercise among the elderly has focused predominantly on the effects of aerobic exercise . In the present study , psychological and behavioral adaptations in response to 12-weeks of strength training were examined in medically healthy but sedentary 42 older adults ( mean age = 68 years ) . The purpose of this study was to evaluate the effects of high and low intensity resistance training intensity on a ) muscular fitness , b ) psychological affect , and c ) neurocognitive functioning . Subjects were r and omly assigned to high intensity/low volume ( EXH : 2 sets of 8 to 10 repetitions for 75 to 85 % of 1 RM ) , low intensity/high volume ( EXL : 2 sets of 14 to 16 repetitions for 55 to 65 % of 1 RM ) , or no exercise control programs . Prior to and following the 12-week program , subjects underwent comprehensive physiological and psychological evaluations . Physiological assessment included measurements of blood pressure , heart rate , arm and leg muscle strength , body composition , and oxygen consumption ( VO2max ) . Psychological measures included evaluations of mood , anxiety , and physical self-efficacy as well as cognitive functioning . The results of this study indicated that both high and low intensity strength programs were associated with marked improvements in physiological fitness and psychological functioning . Specifically , subjects in the strength training programs increased overall muscle strength by 38.6 % and reduced percent body fat by 3.0 % . Favorable psychological changes in the strength-trained subjects included improvements in positive and negative mood , trait anxiety , and perceived confidence for physical capability . The treatment effects of neurocognitive functioning were not significant . In summary , this study demonstrated that participation in 12-weeks of high or low intensity strength training can improve overall physical fitness , mood , and physical self-efficacy in older adults while cognitive functioning remains constant The effects of aerobic exercise training in a sample of 85 older adults were investigated . Ss were assigned r and omly to either an aerobic exercise group , a nonaerobic exercise ( yoga ) group , or a waiting-list control group . Following 16 weeks of the group-specific protocol , all of the older Ss received 16 weeks of aerobic exercise training . The older adults demonstrated a significant increase in aerobic capacity ( cardiorespiratory fitness ) . Performance on reaction-time tests of attention and memory retrieval was slower for the older adults than for a comparison group of 24 young adults , and there was no improvement in the older adults ' performance on these tests as a function of aerobic exercise training . Results suggest that exercise-related changes in older adults ' cognitive performance are due either to extended periods of training or to cohort differences between physically active and sedentary individuals The effect of aerobic exercise on reaction time in older women was investigated . 14 women ( M age = 65 yr . ) were carefully screened for health status and lifestyle , then assigned to a r and om order of the exercise and control groups ( ns = 7 ) . Pre- and posttraining tests of aerobic capacity , simple reaction time , and choice reaction time were administered . The exercise group rode a stationary bicycle ergometer for 8 consecutive weeks for 3 35- to 40-min . sessions per week . There were no significant pretraining differences between groups on simple reaction time , choice reaction time , or estimated VO2 max . No posttraining differences for simple and choice reaction time were found even though the exercise group had a significantly higher VO2 max than the controls . Contrary to some other findings , the data indicate that reaction time may be independent of aerobic training in healthy older women BACKGROUND Obesity impairs cognition and health-related quality of life ( HRQOL ) in older adults ; however , the appropriate treatment of obese older adults remains controversial . OBJECTIVE The objective was to determine the independent and combined effects of weight loss and exercise on cognition , mood , and HRQOL in obese older adults . DESIGN One hundred seven frail , obese older adults were r and omly assigned to a control , weight-management ( diet ) , exercise , or weight-management-plus-exercise ( diet-exercise ) group for 1 y. In this secondary analysis , main outcomes were Modified Mini-Mental State Examination ( 3MS ) and total Impact of Weight on Quality of Life-Lite ( IWQOL ) scores . Other outcomes included Word Fluency Test , Trail Making Test Parts A and B , and Geriatric Depression Scale ( GDS ) scores . RESULTS Scores on the 3MS improved more in the diet ( mean ± SE : 1.7 ± 0.4 ) , exercise ( 2.8 ± 0.4 ) , and diet-exercise ( 2.9 ± 0.4 ) groups than in the control group ( 0.1 ± 0.4 ) ( between-group P = 0.0001 - 0.04 ) ; scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group . Scores on the Word Fluency Test improved more in the exercise ( 4.1 ± 0.8 ) and diet-exercise ( 4.2 ± 0.7 ) groups than in the control group ( -0.8 ± 0.8 ; both P = 0.001 ) . For the Trail Making Test Part A , scores in the diet-exercise group ( -11.8 ± 1.9 ) improved more than in the control group ( -0.8 ± 1.9 ) ( P = 0.001 ) ; a similar finding was observed for the Trail Making Test Part B. Scores on the IWQOL improved more in the diet ( 7.6 ± 1.6 ) , exercise ( 10.1 ± 1.6 ) , and diet-exercise ( 14.0 ± 1.4 ) groups than in the control group ( 0.3 ± 1.6 ) ( P = 0.0001 - 0.03 ) ; scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group . In the diet-exercise group , peak oxygen consumption and strength changes were independent predictors of 3MS changes ; weight and strength changes were independent predictors of IWQOL changes . GDS scores did not change . CONCLUSIONS Weight loss and exercise each improve cognition and HRQOL , but their combination may provide benefits similar to exercise alone . These findings could inform practice guidelines with regard to optimal treatment strategies for obese older adults . This trial was registered at clinical trials.govas NCT00146107 AIM To compare the effect of multicomponent and resistance training and detraining on cognition and depressive symptoms in oldest-old community-dwelling people . METHODS A total of 69 sedentary older adults aged older than 80 years were assessed and r and omized into three groups ( control , multicomponent and resistance training ) . The multicomponent group performed protocol consisting of aerobic , strength and balance exercises . The resistance group participated in strength exercises using six machines . The control group did not perform any intervention . The training sessions had progressive intensity , lasted 16 weeks and included three sessions per week . The volunteers were assessed at baseline , at the end of the 16-week training sessions and after the 6-week detraining period . The assessment consisted of anamneses , Geriatric Depression Scale and cognition ( Montreal Cognitive Assessment , Clock Drawing Test , verbal fluency and dual task ) . RESULTS There were no significant differences between groups and times in any of variables ; however , the adherence to training was low , mainly in the multicomponent group . CONCLUSIONS R and omized controlled trials using adherence strategies and longer times comparing training variations are required to verify which training protocol s are more effective and consistent on cognition and depression in oldest-old people |
12,438 | 26,273,071 | Conclusion : Field triage compared to referral via a spoke centre leads to a lower 30-day mortality in STEMI patients . | Aims : The purpose of this study was to determine whether direct ambulance transport of ST-elevation myocardial infa rct ion ( STEMI ) patients to a percutaneous coronary intervention ( PCI ) hospital ( field triage ) leads to a lower 30-day mortality compared to transport via a referral non-PCI hospital ( referral via a spoke centre ) in STEMI patients . | Background — Traditional reperfusion options for patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) presenting to non- primary percutaneous coronary intervention (PPCI)-capable hospitals generally include onsite fibrinolytics or emergency transfer for PPCI . A third option , involving interventionalist transfer , was examined in the REVERSE-STEMI study . Methods and Results — A total of 334 patients with acute STEMI who presented to 5 referral hospitals with angiographic facilities but without interventionalists qualified for PPCI were r and omized to receive PPCI with either an interventionalist- ( n=165 ) or a patient-transfer ( n=169 ) strategy . The primary end point of door-to-balloon ( D2B ) time and secondary end points of left ventricular ejection fraction and major adverse cardiac events ( MACE ) at 1-year clinical follow-up were compared between the 2 groups . Compared with the patient-transfer strategy , the interventionalist-transfer strategy result ed in a significantly shortened D2B time ( median , 92 minutes versus 141 minutes ; P<0.0001 ) , with more patients having first balloon angioplasty within 90 minutes ( 21.2 % versus 7.7 % , P<0.001 ) . This treatment strategy also was associated with higher left ventricular ejection fraction ( 0.60±0.07 versus 0.57±0.09 , P<0.001 ) and improved 1-year MACE-free survival ( 84.8 % versus 74.6 % , P=0.019 ) . Multivariate Cox proportional hazards modeling revealed that the interventionalist-transfer strategy was an independent factor for reduced risk of composite MACE ( hazard ratio , 0.63 ; 95 % CI , 0.45 to 0.88 ; P=0.003 ) . Conclusions — The interventionalist-transfer strategy for PPCI may be effective in improving the care of patients with STEMI presenting to a non-PPCI-capable hospital , particularly in a congested cosmopolitan region where patient transfers could be prolonged . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00713557 AIMS We investigated the net benefit in the outcome of reducing treatment delay through field triage and emergency department ( ED ) bypass in patients with ST-elevation myocardial infa rct ion ( STEMI ) treated with primary angioplasty . METHODS AND RESULTS In a prospect i ve registry study , consecutive patients with suspected STEMI were assigned to : ( i ) pre-hospital ECG and triage or ( ii ) ECG and triage at the closest ED , solely based on ambulance availability . Four district hospitals and one regional heart centre serviced the 890,000 population metropolitan area and primary angioplasty was the only reperfusion strategy employed . Baseline characteristics were similar in STEMI patients triaged in the field ( 108 ) and the EDs ( 193 ) . Symptom onset to balloon times : 154 [ inter-quartile range ( IQR ) 120 - 233 ) vs. 249 ( IQR 184 - 405 ) min ( P<0.001 ) and peak creatine kinase in early presenters ( < 2 h ) : 1435 ( 95 % CI : 904 - 1966 ) U/L vs. 2320 ( 95 % CI : 1881 - 2762 ) U/L ( P=0.009 ) were lower in field- than in ED-triaged patients . Mortality in the PCI treated were 1.1 and 8.2 % [ P=0.025 , RR 0.14 ( 95 % CI : 0.01 - 1.08 ) ] and overall mortality were 1.9 and 7.3 % [ P=0.046 , RR 0.26 ( 95 % CI : 0.05 - 1.11 ) ] . CONCLUSION Field-triage and ED bypass were feasible means of reducing treatment delay in patients with suspected STEMI and result ed in smaller infa rct size in early presenters and a trend towards a reduction in mortality Objective To investigate the potential benefit of an earliest possible out-of-hospital start of abciximab ( ReoPro ) therapy in ST-elevation myocardial infa rct ion ( STEMI ; Lilly , Bad Homburg , Germany ) and planned primary percutaneous intervention compared with periprocedural abciximab treatment on reperfusion and clinical outcome . Methods R and omization of one hundred and one patients with STEMI to prehospital or periprocedural abciximab treatment . Evaluation of thrombolysis in myocardial infa rct ion ( TIMI ) flow , ST-segment resolution , myocardial blush grade , and maximal creatine kinase release before and after as well as clinical follow-up until 6 months after the index event . Results Prehospital abciximab ( group 1 ) was initiated a median of 101 min ( 37–165 min ) earlier compared with periprocedural treatment ( group 2 ) . Initial TIMI 3 flow ( 24 vs. 15 % , P = NS ) , ST-segment resolution before percutaneous coronary intervention ( PCI ) ( < 30 % : 33 vs. 46 % , P = NS ; > 70 % : 38 vs. 33 % , P = NS ) , post-PCI myocardial blush grade 2 and 3 ( 72 vs. 75 % , P = NS ) , maximal cardiac enzyme release ( creatinine kinase MB median 77 U/l ; range 33–137 vs. 74 U/l ; range 39–143 U/l , P = NS ) , and 6 months follow-up ( recurrent myocardial infa rct ion or repeat coronary intervention , and PCI , need for coronary bypass surgery ) did not differ significantly between both treatment groups . Conclusion Prehospital intravenous administration of abciximab , although safe and feasible in a trained surrounding , does not add angiographic or clinical benefit to patients with STEMI BACKGROUND Although both prehospital fibrinolysis and primary angioplasty provide a clinical benefit over in-hospital fibrinolysis in acute myocardial infa rct ion , they have not been directly compared . Our aim was to find out whether primary angioplasty was better than prehospital fibrinolysis . METHODS We did a r and omised multicentre trial of 840 patients ( of 1200 planned ) who presented within 6 h of acute myocardial infa rct ion with ST-segment elevation , initially managed by mobile emergency-care units . We assigned patients to prehospital fibrinolysis ( n=419 ) with accelerated alteplase or primary angioplasty ( n=421 ) , and transferred all to a centre with access to emergency angioplasty . Our primary endpoint was a composite of death , non-fatal reinfa rct ion , and non-fatal disabling stroke at 30 days . Analyses were by intention to treat . FINDINGS The median delay between onset of symptoms and treatment was 130 min in the prehospital-fibrinolysis group and 190 min ( time to first balloon inflation ) in the primary -angioplasty group . Rescue angioplasty was done in 26 % of the patients in the fibrinolysis group . The rate of the primary endpoint was 8.2 % ( 34 patients ) in the prehospital-fibrinolysis group and 6.2 % ( 26 patients ) in the primary -angioplasty group ( risk difference 1.96 , 95 % CI -1.53 to 5.46 ) . 16 ( 3.8 % ) patients assigned prehospital fibrinolysis and 20 ( 4.8 % ) assigned primary angioplasty died ( p=0.61 ) . INTERPRETATION A strategy of primary angioplasty was not better than a strategy of prehospital fibrinolysis ( with transfer to an interventional facility for possible rescue angioplasty ) in patients presenting with early myocardial infa rct ion OBJECTIVE To assess the safety and feasibility of acute transport followed by rescue percutaneous transluminal coronary angioplasty ( PTCA ) or primary PTCA in patients with acute myocardial infa rct ion initially admitted to a hospital without PTCA facilities . DESIGN In a multicentre r and omised open trial , three regimens of treatment of acute large myocardial infa rct ion were compared for patients admitted to hospitals without angioplasty facilities : thrombolytic treatment with alteplase ( 75 patients ) , alteplase followed by transfer to the PTCA centre and ( if indicated ) rescue PTCA ( 74 patients ) , or transfer for primary PTCA ( 75 patients ) . RESULTS Between 1995 and 1997 224 patients were included . Baseline characteristics were distributed evenly . Transport to the PTCA centre was without severe complications in all patients . Mean ( SD ) delay from onset of symptoms to r and omisation was 130 ( 75 ) minutes and from r and omisation to angiography 90 ( 25 ) minutes . Death or recurrent infa rct ion within 42 days occurred in 12 patients in the thrombolysis group , in 10 patients in the rescue PTCA group , and in six patients in the primary PTCA group . These differences were not significant . CONCLUSIONS Acute transfer for rescue PTCA or primary PTCA in patients with extensive myocardial infa rct ion is feasible and safe . Efficacy of rescue PTCA or primary PTCA in this setting will have to be tested in larger series before this approach can be implemented as “ routine treatment ” for patients with extensive myocardial infa rct ion BACKGROUND For the treatment of myocardial infa rct ion with ST-segment elevation , primary angioplasty is considered superior to fibrinolysis for patients who are admitted to hospitals with angioplasty facilities . Whether this benefit is maintained for patients who require transportation from a community hospital to a center where invasive treatment is available is uncertain . METHODS We r and omly assigned 1572 patients with acute myocardial infa rct ion to treatment with angioplasty or accelerated treatment with intravenous alteplase ; 1129 patients were enrolled at 24 referral hospitals and 443 patients at 5 invasive-treatment centers . The primary study end point was a composite of death , clinical evidence of reinfa rct ion , or disabling stroke at 30 days . RESULTS Among patients who underwent r and omization at referral hospitals , the primary end point was reached in 8.5 percent of the patients in the angioplasty group , as compared with 14.2 percent of those in the fibrinolysis group ( P=0.002 ) . The results were similar among patients who were enrolled at invasive-treatment centers : 6.7 percent of the patients in the angioplasty group reached the primary end point , as compared with 12.3 percent in the fibrinolysis group ( P=0.05 ) . Among all patients , the better outcome after angioplasty was driven primarily by a reduction in the rate of reinfa rct ion ( 1.6 percent in the angioplasty group vs. 6.3 percent in the fibrinolysis group , P<0.001 ) ; no significant differences were observed in the rate of death ( 6.6 percent vs. 7.8 percent , P=0.35 ) or the rate of stroke ( 1.1 percent vs. 2.0 percent , P=0.15 ) . Ninety-six percent of patients were transferred from referral hospitals to an invasive-treatment center within two hours . CONCLUSIONS A strategy for reperfusion involving the transfer of patients to an invasive-treatment center for primary angioplasty is superior to on-site fibrinolysis , provided that the transfer takes two hours or less Background — The value of prehospital initiation of glycoprotein IIb/IIIa inhibitors remains a controversial issue . We sought to investigate whether in-ambulance initiation of abciximab in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) improves ST-segment elevation resolution ( STR ) after primary percutaneous coronary intervention ( PCI ) . Methods and Results — MISTRAL ( Myocardial Infa rct ion with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace ) is a prospect i ve , r and omized , double-blind study . Two hundred and fifty-six patients with acute STEMI were allocated to receive abciximab either in the ambulance ( ambulance group , n=127 ) or in the catheterization laboratory ( hospital group , n=129 ) . The primary end point was complete ( > 70 % ) STR after PCI . Complete STR was not significantly different between the 2 groups ( before PCI , 21.6 % versus 15.5 % , P=0.28 ; after PCI , 70.3 % versus 65.8 % , P=0.49 ) . Thrombolysis In Myocardial Infa rct ion ( TIMI ) 2 to 3 flow rates before PCI tended to be higher in the ambulance group ( 46.8 % versus 35 % , P=0.08 ) but not after PCI ( 70.3 % versus 65.8 % , P=0.49 ) . Slow flow tended to be lower ( 5.6 % versus 13.4 % , P=0.07 ) , and distal embolization occurred significantly less often in the ambulance group ( 8.1 % versus 21.1 % , P=0.008 ) . One- and 6-month major adverse cardiac event rates were low and similar in both groups . Conclusions — Early ambulance administration of abciximab in STEMI did not improve either STR or TIMI flow rate after PCI . However , it tended to improve TIMI flow pre-PCI and decreased distal embolization during procedure . Larger studies are needed to confirm these results . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00638638 Primary percutaneous coronary intervention ( PCI ) is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) . We evaluated whether presentation of patients with STEMI to a noninterventional facility requiring transfer for primary PCI compared to direct admission to a PCI center has an impact on clinical outcomes . Of 3,602 patients enrolled in the multicenter , prospect i ve HORIZONS-AMI trial , 988 ( 24.7 % ) were transferred for primary PCI and 2,614 were directly admitted to an interventional hospital . Clinical outcomes at 30 days and 1 year were evaluated . Median time to reperfusion in patients with transfer was 67 minutes longer compared to patients without transfer ( 272 vs 205 minutes , p < 0.001 ) , and first door-to-balloon time was 47 minutes longer ( 134 vs 87 minutes , p < 0.001 ) . At 30 days and 1 year there were no significant differences between patients with and without transfer in the rates of major adverse cardiac events ( 30 days 5.8 % vs 5.4 % , p = 0.68 ; 1 year 11.6 % vs 12.0 % , p = 0.74 ) , major bleeding ( 30 days 7.3 % vs 6.9 % , p = 0.66 ; 1 year 7.9 % vs 7.4 % , p = 0.63 ) , or mortality ( 30 days 2.6 % vs 2.6 % , p = 0.92 ; 1 year 4.0 % vs 4.2 % , p = 0.81 ) . In transfer and nontransfer patients use of bivalirudin compared to unfractionated heparin plus glycoprotein IIb/IIIa inhibitor was associated with lower rates of bleeding , cardiac death , and net adverse clinical events . In conclusion , in the HORIZONS-AMI trial , 30-day and 1-year survival rates and clinical outcomes were comparable in patients with STEMI requiring and not requiring transfer for primary PCI OBJECTIVES We have performed a retrospective analysis of the data stratified by time to treatment and by enrollment site : percutaneous coronary intervention hospitals ( PCIH ) , nonpercutaneous coronary intervention hospitals ( NoPCIH ) , or in a pre-hospital setting ( PreH ) . BACKGROUND The ASSENT-4 PCI ( Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention ) trial intended to test the hypothesis that in ST-segment elevation myocardial infa rct ion ( STEMI ) patients an upfront fibrinolytic bolus before PCI ( " facilitated PCI " ) compared with primary PCI would benefit STEMI patients facing a long pre-PCI delay . METHODS Seven hundred forty-nine patients ( 45 % ) presented directly to PCIH , 578 ( 34 % ) presented to NoPCIH , and 334 ( 20 % ) were r and omized and initially treated in the PreH setting . RESULTS Patients in the PreH-facilitated group had the shortest delays ( pain-to-fibrinolytic treatment 125 min ) and the lowest 90-day mortality ( 3.1 % ) . Among patients r and omized to primary PCI , the shortest time from pain to first balloon was similarly in the PreH group ( 223 min ) . They had the lowest mortality of the primary PCI patient groups ( 4.1 % ) . The highest mortality ( 8.4 % ) was in patients presenting to a PCIH and assigned to the facilitated strategy . Their pain-to-lysis time was 174 min and pain-to-PCI time 266 min ( or 92 min after lysis ) . CONCLUSIONS Few patients fit the target population , long delays to PCI for whom facilitated PCI was design ed . Patients treated early after pain onset in the PreH setting do well after a facilitated approach . Despite limitations of post hoc subgroup analysis , these observations suggest caution in extrapolating the results of the ASSENT-4 trial to the " real world " where many patients might have potentially short pain-to-fibrinolysis time but are facing a long transport time to primary PCI In animal studies , transthoracic ultrasound and microbubbles have shown to dissolve thrombi in ST elevation myocardial infa rct ion ( STEMI ) . To examine this effect in patients , we have initiated the Sonolysis trial . In this pilot study of 10 patients with a first acute STEMI , we investigated the safety and feasibility of this trial . After pretreatment in the ambulance , five patients were r and omized to receive microbubbles with three-dimensional ( 3-D ) guided high mechanical index impulses ( 1.18 ) for 15 min , whereas the control group received placebo without ultrasound . Subsequently , primary percutaneous coronary intervention ( PPCI ) was performed , if indicated . All patients successfully underwent study treatment and PPCI . No significant difference between treatment and control group in safety ( minor adverse events 2/5 vs. 2/5 , p = NS ) and outcome ( TIMI III flow 3/5 vs. 1/5 respectively , p = 0.23 ) was recorded . These results demonstrate that the study protocol is feasible in the acute cardiac care setting and safe during treatment and follow-up Outcomes were evaluated in 1,841 consecutive patients with acute myocardial infa rct ion treated with primary percutaneous coronary intervention from 1984 to 2000 comparing patients transferred from community hospitals ( n = 680 ) with patients presenting locally ( n = 1,161 ) . Baseline variables were similar except transferred patients had fewer prior infa rct ions ( 13 % vs 21 % , p < 0.001 ) and underwent less prior bypass surgery ( 2.8 % vs 6.0 % , p = 0.002 ) . Median times from symptom onset to emergency department arrival were similar , but door-to-balloon times and reperfusion times were approximately 1 hour longer in transferred patients ( 2.8 vs 1.9 hours [ p < 0.001 ] and 4.5 vs 3.5 hours [ p < 0.001 ] , respectively ) . Despite longer treatment times , there were no significant differences between transferred and nontransferred patients in 30-day mortality ( 7.6 % vs 8.1 % , p = 0.73 ) , reinfa rct ion , urgent target vessel revascularization , stroke , and late mortality . After adjusting for differences in baseline variables , mortality remained similar between transferred and nontransferred patients ( odds ratio 0.90 , 95 % confidence interval 0.59 to 1.36 ) . Peak cardiac enzyme values were higher in transferred patients , but there were no differences in 6-month ejection fractions between groups . In conclusion , patients transferred from community hospitals for primary percutaneous coronary intervention have almost 1-hour additional treatment delay , but this does not appear to have a major adverse effect on clinical outcomes . These data should encourage further r and omized trials to evaluate the role of transfer for mechanical reperfusion in patients presenting to community hospitals with acute myocardial infa rct ion AIMS Early and complete reperfusion is the main treatment goal in ST-elevation myocardial infa rct ion ( STEMI ) . The timely optimal reperfusion strategy might be a pre-hospital initiated pharmacological reperfusion with subsequent facilitated percutaneous coronary intervention ( PCI ) . This approach has been compared with pre-hospital combination-fibrinolysis only to determine whether either one of these methods offer advantages with respect to final infa rct size . METHODS AND RESULTS Patients with STEMI were r and omized to either pre-hospital combination-fibrinolysis ( half-dose reteplase+abciximab ) with st and ard care ( n=82 ) or pre-hospital combination-fibrinolysis with facilitated PCI ( n=82 ) . Primary endpoint was the infa rct size assessed by delayed enhancement magnetic resonance . Secondary endpoints were ST-segment resolution at 90 min and a composite of death , re-myocardial infa rct ion , major bleeding , and stroke at 6 months . The infa rct size was lower after facilitated PCI with 5.2 % [ interquartile range ( IQR ) 1.3 - 11.2 ] as opposed to 10.4 % ( IQR 3.4 - 16.3 ) after pre-hospital combination-fibrinolysis ( P=0.001 ) . Complete ST-segment resolution was 80.0 % after facilitated PCI vs. 51.9 % after pre-hospital combination-fibrinolysis ( P<0.001 ) . After facilitated PCI , there was a trend towards a lower event rate in the combined clinical endpoint ( 15 vs. 25 % , P=0.10 , relative risk 0.57 , 95 % CI 0.28 - 1.13 ) . CONCLUSION In patients with STEMI , additional facilitated PCI after pre-hospital combination-fibrinolysis results in an improved tissue perfusion with subsequent smaller infa rct size as opposed to pre-hospital combination-fibrinolysis alone . This translates into a trend towards a better clinical outcome BACKGROUND Primary percutaneous coronary intervention ( PCI ) is shown to be the most effective reperfusion strategy in acute myocardial infa rct ion . The aim of this multicentre national r and omized mortality trial was to test whether the nationwide change in treatment guidelines ( transportation of all patients to PCI centres ) was warranted . METHODS The PRAGUE-2 study r and omized 850 patients with acute ST elevation myocardial infa rct ion presenting within < 12 h to the nearest community hospital without a catheter laboratory to either thrombolysis in this hospital ( TL group , n=421 ) or immediate transport for primary percutaneous coronary intervention ( PCI group , n=429 ) . The primary end-point was 30-day mortality . Secondary end-points were : death/reinfa rct ion/stroke at 30 days ( combined end-point ) and 30-day mortality among patients treated within 0 - 3 h and 3 - 12 h after symptom onset . Maximum transport distance was 120 km . RESULTS Five complications ( 1.2 % ) occurred during the transport . R and omization-balloon time in the PCI group was 97+/-27 min , and r and omization-needle time in the TL group was 12+/-10 min . Mortality at 30 days was 10.0 % in the TL group compared to 6.8 % mortality in the PCI group ( P=0.12 , intention-to-treat analysis ) . Mortality of 380 patients who actually underwent PCI was 6.0 % vs 10.4 % mortality in 424 patients who finally received TL ( P<0.05 ) . Among 299 patients r and omized > 3 h after the onset of symptoms , the mortality of the TL group reached 15.3 % compared to 6 % in the PCI group ( P<0.02 ) . Patients r and omized within <3 h of symptom onset ( n=551 ) had no difference in mortality whether treated by TL ( 7.4 % ) or transferred to PCI ( 7.3 % ) . A combined end-point occurred in 15.2 % of the TL group vs 8.4 % of the PCI group ( P<0.003 ) . CONCLUSIONS Long distance transport from a community hospital to a tertiary PCI centre in the acute phase of AMI is safe . This strategy markedly decreases mortality in patients presenting > 3 h after symptom onset . For patients presenting within <3 h of symptoms , TL results are similar results to long distance transport for PCI BACKGROUND Primary coronary angioplasty is an effective reperfusion strategy in acute myocardial infa rct ion . However , its availability is limited , and transporting patients to an angioplasty centre in the acute phase of myocardial infa rct ion has not yet been proved safe . METHODS The PRAGUE study ( PRimary Angioplasty in patients transferred from General community hospitals to specialized PTCA Units with or without Emergency thrombolysis ) compared three reperfusion strategies in patients with acute myocardial infa rct ion , presenting within 6 h of symptom onset at community hospitals without a catheterization laboratory : group A - thrombolytic therapy in community hospitals ( n=99 ) , group B - thrombolytic therapy during transportation to angioplasty ( n=100 ) , group C - immediate transportation for primary angioplasty without pre-treatment with thrombolysis ( n=101 ) . RESULTS No complications occurred during transportation in group C. Two ventricular fibrillations occurred during transportation in group B. Median admission-reperfusion time in transported patients ( group B 106 min , group C 96 min ) compared favourably with the anticipated > 90 min in group A. The combined primary end-point ( death/reinfa rct ion/stroke at 30 days ) was less frequent in group C ( 8 % ) compared to groups B ( 15 % ) and A ( 23 % , P<0 . 02 ) . The incidence of reinfa rct ion was markedly reduced by transport to primary angioplasty ( 1 % in group C vs 7 % in group B vs 10 % in group A , P<0.03 ) . CONCLUSIONS Transferring patients from community hospitals to a tertiary angioplasty centre in the acute phase of myocardial infa rct ion is feasible and safe . This strategy is associated with a significant reduction in the incidence of reinfa rct ion and the combined clinical end-point of death/reinfa rct ion/stroke at 30 days when compared to st and ard thrombolytic therapy at the community hospital |
12,439 | 18,349,093 | Generally there were modest positive effects on psychological outcomes such as worry and anxiety , behavioral outcomes have shown mixed results , and clinical outcomes were less well studied .
One systematic review , 1 r and omized controlled trial , and 14 other studies assessed consumer information needs and found in general that genetics knowledge was reported to be low but that attitudes were generally positive . | CONTEXT The greatest public health benefit of advances in underst and ing the human genome may be realized for common chronic diseases such as cardiovascular disease , diabetes mellitus , and cancer .
Attempts to integrate such knowledge into clinical practice are still in the early stages , and as a result , many questions surround the current state of this translation .
OBJECTIVE To synthesize current information on genetic health services for common adult-onset conditions by examining studies that have addressed the outcomes , consumer information needs , delivery , and challenges in integrating these services . | Genetic testing for inherited germ-line mutations associated with cancer susceptibility is an emerging technology in medical practice . Limited information is currently available about physician use of cancer susceptibility tests ( CSTs ) . In 1999 - 2000 , a nationally representative survey was conducted to estimate prevalence of CST use by United States physicians and assess demographic , training , practice setting , and practice patterns associated with use . A stratified r and om sample of clinicians in eight specialties was selected from a file of all licensed physicians . In total , 1251 physicians , including 820 in primary care and 431 in tertiary care , responded to a 15-min question naire by mail , telephone , fax , or Internet ( response rate = 71.0 % ) . In the previous 12 months , 31.2 % [ 95 % confidence interval ( CI ) , 28.5 - 33.9 ] overall , including 30.6 % ( 95 % CI , 27.5 - 33.7 ) in primary care and 33.4 % ( 95 % CI , 27.9 - 38.9 ) in tertiary care , had ordered CSTs or referred patients elsewhere for risk assessment or testing . More physicians referred patients elsewhere [ 26.7 % ( 95 % CI , 24.2 - 29.2 ) ] than directly ordered tests [ 7.9 % ( 95 % CI , 6.3 - 9.5 ) ] . Factors associated with ordering or referring included practice location in the Northeast [ odds ratio ( OR ) , 2.30 ; 95 % CI , 1.46 - 3.63 % ] , feeling qualified to recommend CSTs ( OR , 1.96 ; 95 % CI = 1.41 - 2.72 ) , receiving CST advertising material s ( OR , 1.97 ; 95 % CI , 1.40 - 2.78 % ) , and most notably , having patients who asked whether they can or should get tested ( OR , 5.52 ; 95 % CI , 3.97 - 7.67 % ) . Lower CST use was associated with not knowing if there were local testing and counseling facilities ( OR , 0.39 ; 95 % CI , 0.23 - 0.66 % ) . These findings underscore the importance of establishing effective clinical approaches to test use and promoting physician education to facilitate communication with patients about cancer genetics Purpose : Genetic screening can enable timely detection and treatment of hereditary hemochromatosis ( HH ) . Little is known about patient acceptability of DNA testing as compared to conventional phenotypic testing . Methods : Within the HEIRS Study , a large primary -care screening study of HH and iron overload , we r and omly assigned participants to receive brief information on either HH genotypic or phenotypic testing , and assessed the willingness to accept this test . The study was design ed to recruit an equal number of African Americans and Caucasians . Results : A total of 2500 participants were recruited from waiting rooms of primary care practice s ; 2165 participants who self-identified as African Americans and Caucasians were included in the analyses . Overall , 56 % had accepted a genotypic test versus 58 % for a phenotypic test . Adjusting for Field Center ( FC ) , age , gender , race , educational attainment , global health rating , and knowledge of the test , the odds ratio of accepting a genotypic versus phenotypic test was 0.85 ( 95 % CI : 0.71 , 1.02 ; P = 0.078 ) . Characteristics associated with test acceptance were age 45–64 years , female gender , Caucasian race , self-rated health less than “ very good ” , and knowledge of the test . Test acceptance was associated with interest in knowing more about health ( 81 % ) and in helping family members ( 71 % ) . Refusal reasons included a need to talk with a doctor ( 44 % ) , concern about privacy ( 32 % ) , and dislike of blood drawing ( 29 % ) . Conclusion : In this diverse sample of primary care patients , stated acceptance of genotypic testing for HH mutations was similar to phenotypic testing for blood iron . Patient education regarding the nature of test , importance of disease detection , and privacy protection appear to be essential for achieving high rates of screening participation OBJECTIVE To examine the relationship between health beliefs and attitudes toward colorectal cancer screening , strength of family history risk , and being appropriately screened for colorectal cancer . METHODS In February 2004 , 7000 r and omly selected members of a multi-specialty group practice located in Boston , MA were mailed a brief survey that was used to ascertain colorectal cancer family history . A follow-up survey that contained questions representing selected constructs of the Health Belief Model , Theory of Planned Behavior , and healthcare experiences was then mailed to all 355 individuals who reported a family history in the initial survey and 710 r and omly selected participants with no colorectal cancer family history . RESULTS Participants who were appropriately screened had higher mean scores for perceived cancer risk , subjective norms , and perceived benefits and lower scores for perceived barriers . Multivariate findings indicate that having high perceptions of risk for colorectal cancer was a significant correlate of being screened appropriately among individuals with a strong family history . CONCLUSIONS For those at greatest colorectal cancer risk due to family history , ensuring that these individuals underst and their personal risk might lead to increased colorectal cancer screening participation . Future intervention research is warranted to examine if raising perceptions of risk can increase screening behaviors in individuals with colorectal cancer risk due to family history Background — Pharmacogenetic-guided dosing of warfarin is a promising application of “ personalized medicine ” but has not been adequately tested in r and omized trials . Methods and Results — Consenting patients ( n=206 ) being initiated on warfarin were r and omized to pharmacogenetic-guided or st and ard dosing . Buccal swab DNA was genotyped for CYP2C9 * 2 and CYP2C9 * 3 and VKORC1C1173 T with a rapid assay . St and ard dosing followed an empirical protocol , whereas pharmacogenetic-guided dosing followed a regression equation including the 3 genetic variants and age , sex , and weight . Prothrombin time international normalized ratio ( INR ) was measured routinely on days 0 , 3 , 5 , 8 , 21 , 60 , and 90 . A research pharmacist unblinded to treatment strategy managed dose adjustments . Patients were followed up for up to 3 months . Pharmacogenetic-guided predicted doses more accurately approximated stable doses ( P<0.001 ) , result ing in smaller ( P=0.002 ) and fewer ( P=0.03 ) dosing changes and INRs ( P=0.06 ) . However , percent out-of-range INRs ( pharmacogenetic=30.7 % , st and ard=33.1 % ) , the primary end point , did not differ significantly between arms . Despite this , when restricted to wild-type patients ( who required larger doses ; P=0.001 ) and multiple variant carriers ( who required smaller doses ; P<0.001 ) in exploratory analyses , results ( pharmacogenetic=29 % , st and ard=39 % ) achieved nominal significance ( P=0.03 ) . Multiple variant allele carriers were at increased risk of an INR of ≥4 ( P=0.03 ) . Conclusions — An algorithm guided by pharmacogenetic and clinical factors improved the accuracy and efficiency of warfarin dose initiation . Despite this , the primary end point of a reduction in out-of-range INRs was not achieved . In subset analyses , pharmacogenetic guidance showed promise for wild-type and multiple variant genotypes Purpose : To determine the genetics education needs and priorities of dietitians , occupational therapists , physical therapists , psychologists , speech- language -hearing specialists , and social workers . Methods : A r and om sample mail survey of 3600 members of 6 national health professional organizations was undertaken in 1998 and result ed in 1958 responses . Results : A majority worked with clients with genetic conditions , most were providing genetic services to some clients , few had high confidence in providing genetic services , most had little or no education in genetics , and two-thirds wanted continuing education . Conclusion : The study shows a critical need for genetics education of allied and counseling health professionals Genetic testing for an inherited susceptibility to cancer is an emerging technology in medical practice . Little information is currently available about physicians ' attitudes toward these tests . To assess US physicians ' opinions on unresolved issues surrounding genetic testing , a 15‐min survey was administered to a stratified r and om sample of 1,251 physicians from 8 specialties , selected from a file of all licensed physicians in the US ( response rate = 71.0 % ) . Dependent measures included physicians ' attitudes toward genetic counseling and testing qualifications , availability of guidelines , patient confidentiality and insurance discrimination issues , and clinical utility of genetic tests . More than 89 % of physicians reported a need for physician guidelines , 81 % thought that patients with positive genetic test results are at risk for insurance discrimination , and more than 53 % thought that it was difficult to ensure the confidentiality of test results . Almost 25 % indicated that genetic tests for cancer susceptibility have too many inaccurate or ambiguous results ; nearly 75 % thought that clear guidelines are not available for managing patients with positive test results . Only 29 % of physicians reported feeling qualified to provide genetic counseling to their patients . More than 84 % of oncologists considered themselves qualified to recommend genetic testing to their patients compared with 40 % of primary care physicians ( PCPs ) , and 57 % of tertiary care physicians ( TCPs ) . US physicians expressed great uncertainty about issues surrounding genetic testing for cancer susceptibility . Results of this national survey underscore the need to provide physicians with clear guidelines on the use of genetic cancer susceptibility tests and effective medical training on their appropriate implementation . Published 2003 Wiley‐Liss , There is a need to integrate primary - and secondary -care cancer genetic services , but the most appropriate model of service delivery remains unclear . This study reports patients ’ expectations of breast cancer genetic services and a comparison of their satisfaction with two service models . In the first model , risk assessment was carried out using mailed family history data . Women estimated as being at high/moderate risk were offered an appointment at the familial breast cancer clinic , and those at low risk were sent a letter of reassurance . In the second model , all women were seen by a genetic nurse specialist , who assessed risk , referred high/moderate-risk women to the above clinic and discharged those at low risk . Over 60 % of all women in the study regarded access to breast screening by mammogram and regular check-ups as very important . This underlines the dem and for a multidisciplinary service providing both clinical genetic and surgical services . Satisfaction was high with both models of service , although significantly lower among women not at increased cancer risk and thus not offered a clinical check-up and mammography . Increased cancer worry was associated with a greater expressed need for information and for reassurance through follow-up clinical checks and mammography . Better targeting of counselling to the expressed concerns and needs of these women is required to improve the service offered . GPs and patients expressed no clear preference for any specific service location or staffing configuration . The novel community service was less expensive in terms of both staff and patient costs . The potential to decrease health staff/patient contact time and to employ nurse practitioners with both clinical genetic and oncology training should be explored further . The rapidly rising dem and for these services suggests that the evaluation of further new models needs to continue to be given priority to guide the development of cancer genetic services Purpose : Little is known about reasons why eligible breast cancer patients decline BRCA mutation testing . They may withdraw at different stages during genetic counseling for different reasons . We prospect ively studied perceived benefits and barriers to genetic counseling and BRCA testing in 102 newly diagnosed breast cancer patients approached for genetic counseling at the start of radiotherapy . Methods : Patients completed question naires and participated in interviews at different stages of the counseling protocol . Results : Participation was not influenced by distress , knowledge about hereditary breast cancer , previous genetic testing in relatives , or perceived risks and barriers . Immediate decliners ( n = 23 ) do not believe genetic testing is relevant for them . Patients who decline after pedigree compilation ( n = 14 ) are more hesitant and anxious about the influence of the test result on their future often wishing to postpone further testing . Late decliners ( n = 7 ) withdraw afraid of the test result and /or after a relative 's objection . These decliners are not easily identified upon approach because they are similar to patients who receive a DNA test result ( n = 58 ) . Notwithst and ing their decline , 81 % agreed to the timing or would have preferred an earlier approach for genetic counseling . Conclusion : Decliners may make more informed decisions after tailored health education , including adequate risk information Commercial marketing material s may serve as a source of information for physicians about genetic testing for inherited cancer susceptibility ( GTICS ) in addition to medical guidelines , continuing education , and journal articles . The primary purpose s of this study were to : ( 1 ) determine the percentage of physicians who received advertisements for GTICS early in the diffusion of commercial GTICS ( 1999–2000 ) ; ( 2 ) assess associated characteristics ; and ( 3 ) measure the perceived importance of commercial advertisements and promotions in physicians ' decisions to recommend testing to patients . A nationally representative , stratified r and om sample of 1,251 physicians from the American Medical Association ( AMA ) Physician Masterfile completed a 15–20 min mixed mode question naire that assessed specialty , previous use of genetic tests , practice characteristics , age , and receipt of advertising material s ( response rate = 71 % ) . Overall , 27.4 % ( n = 426 ) had received advertisements . In multivariate analysis , factors associated with receipt of advertisements included : specialties in obstetrics/gynecology , oncology , or gastroenterology ; past GTICS use , and age 50 + . One of four felt that advertisements would be important in their decision to recommend GTICS . Study results indicate that physicians , particularly in oncology , obstetrics/gynecology , and gastroenterology , began receiving GTICS advertisements commensurate with the early diffusion of commercially available tests into clinical practice . At that time , one‐quarter of the physicians considered advertisements to play an important role in their clinical decision making , suggesting attention to other sources of information and additional factors . Published 2005 Wiley‐Liss , Purpose : We assessed the importance assigned by primary care physicians to eight factors influencing whether they would order a genetic test to individually tailor smoking cessation treatment . Methods : A r and om sample of United States primary care physicians was surveyed about how important each of eight factors were in the decision to order the test . Broadly , these factors included the ability of the test to improve treatment , the patient 's reaction to test results , concern about misuse of test results , and the ability of the physician 's office to manage informed consent for the test . Results : Physicians indicated the most important factor they would consider in ordering a genetic test to tailor smoking cessation treatment was the ability to improve cessation outcomes . However , when told the genotype identified by the test was associated with stigma-inducing mental health conditions , physicians emphasized the importance of possible racial , insurance , and employment discrimination in their decisions . Conclusions : Primary care physicians are eager to improve smoking cessation treatment , but the collateral information generated by genetic testing to tailor treatment may be an impediment unless proper antidiscrimination measures are in place The objective was to evaluate the effect of an assessment strategy using the computer decision support system ( the GRAIDS software ) , on the management of familial cancer risk in British general practice in comparison with best current practice . The design included cluster r and omised controlled trial , and involved forty-five general practice teams in East Anglia , UK . R and omised to GRAIDS ( Genetic Risk Assessment on the Internet with Decision Support ) support ( intervention n=23 ) or comparison ( n=22 ) . Training in the new assessment strategy and access to the GRAIDS software ( GRAIDS arm ) was conducted , compared with an educational session and guidelines about managing familial breast and colorectal cancer risk ( comparison ) were mailed . Outcomes were measured at practice , practitioner and patient levels . The primary outcome measure , at practice level , was the proportion of referrals made to the Regional Genetics Clinic for familial breast or colorectal cancer that were consistent with referral guidelines . Other measures included practitioner confidence in managing familial cancer ( GRAIDS arm only ) and , in patients : cancer worry , risk perception and knowledge about familial cancer . There were more referrals to the Regional Genetics Clinic from GRAIDS than comparison practice s ( mean 6.2 and 3.2 referrals per 10 000 registered patients per year ; mean difference 3.0 referrals ; 95 % confidence interval ( CI ) 1.2–4.8 ; P=0.001 ) ; referrals from GRAIDS practice s were more likely to be consistent with referral guidelines ( odds ratio (OR)=5.2 ; 95 % CI 1.7–15.8 , P=0.006 ) . Patients referred from GRAIDS practice s had lower cancer worry scores at the point of referral ( mean difference −1.44 95 % CI −2.64 to −0.23 , P=0.02 ) . There were no differences in patient knowledge about familial cancer . The intervention increased GPs ' confidence in managing familial cancer . Compared with education and mailed guidelines , assessment including computer decision support increased the number and quality of referrals to the Regional Genetics Clinic for familial cancer risk , improved practitioner confidence and had no adverse psychological effects in patients . Trials are registered under N0181144343 in the UK National Research Register Purpose : The study goals were to ( 1 ) determine the proportion of unselected individuals at increased risk for diseases with known genetic components and ( 2 ) compare the documentation and quality of risk assessment between a question naire , a pedigree interview , and chart review . Methods : Seventy-eight patients seen in a division of internal medicine were r and omized into two groups , which completed a question naire or underwent a pedigree interview . Chart notes were compared to both study tools . Results : Sixty-two ( 79.5 % ) of the 78 participants scored at increased risk for at least one category . Either of the two study tools found significantly more people at high risk ( 48/78 , 61.5 % ) than the chart review ( 31/78 , 39.7 % ) ( P = 0.01 ) . Conclusions : Approximately 20 % of patients in an unselected internal medicine practice were at an increased risk that was not documented in review ed chart notes . Targeted family history analysis reveals patients who require increased medical surveillance , preventive measures , or genetic counseling/testing PURPOSE To prospect ively determine the impact of genetic counseling and testing on risk-reduction strategies and cancer incidence in a cohort of individuals at hereditary risk for breast and ovarian cancer . PATIENTS AND METHODS Two hundred fifty-one individuals with BRCA mutations were identified at a single comprehensive cancer center from May 1 , 1995 , through October 31 , 2000 . Uniform recommendations regarding screening and preventive surgery were provided in the context of genetic counseling . Patients were followed for a mean of 24.8 months ( range , 1.6 to 66.0 months ) using st and ardized question naires , chart review s , and contact with primary physicians . RESULTS Frequency of cancer surveillance by physical examinations and imaging studies increased after genetic counseling and testing . Twenty-one breast , ovarian , primary peritoneal , or fallopian tube cancers were detected after receipt of genetic test results . Among 29 individuals choosing risk-reducing mastectomy after testing , two were found to have occult intraductal breast cancers . Among 90 individuals who underwent risk-reducing salpingo-oophorectomy , one early-stage ovarian neoplasm and one early-stage fallopian tube neoplasm were found . Radiographic or tumor marker-based screening detected six breast cancers , five of which were stage 0/I , one early-stage primary peritoneal cancer , and three stage I or II ovarian cancers . Six additional breast cancers were detected by physical examination between radiographic screening intervals ; four of these six tumors were stage I. No stage III or stage IV malignancies were detected after genetic testing . CONCLUSION This study provides prospect i ve evidence that genetic counseling and testing increased surveillance and led to risk-reducing operations , which result ed in diagnosis of early-stage tumors in patients with BRCA1 and BRCA2 mutations Background and Objectives Although more and more genetic information is available , it is unclear whether this information is helpful for patients . Therefore , we assessed the positive and negative effects of informing obese people about the genetic etiology of being overweight . Design , Participants Two hundred ninety-four obese people were r and omized to 2 interventions ( a 1-session consultation for obese people on how to manage obesity either including genetic information or not ) ; their results were compared to a control group ( 116 ) . Subjects were assessed before and after consultation and 6 months later . Measurements Weight , scales on feeling guilty for being overweight , self-control , negative mood ( primary endpoint ) , body acceptance , restraint eating . Results Both types of consultations were considered helpful by the participants , and had comparable effects on body weight . The consultation with genetic information was rated superior in terms of leading to new insights ( advantage for consultation with genetic information , even 6 months later ; p = 0.046 ) . No negative effects ( e.g. , loss of self-efficacy/self-control , increase of body weight ; all p > 0.20 for interaction consultation × time ) were observed for informing obese people about the genetic etiology of being overweight . The consultation result ed in long-term improvement of negative mood if it included genetic information in the case of participants with a family history of obesity and if it included no genetic information in the case of obese people without a family history of obesity ( p = 0.03 for interaction of group , intervention , and time ) . Conclusions Consultations in obesity can be helpful in general . These consultations should include genetic information if people have a family history of obesity BACKGROUND Offspring of people with type 2 diabetes underestimate their risk of developing the disease and know little about primary prevention . However , education about risk might cause psychological harm . AIM To examine cognitive and psychological effects of education about personal risk . METHOD Patients with type 2 diabetes were recruited from r and omly selected general practice s. One of their adult offspring was r and omly selected and r and omly allocated into one of three groups : 1 . Group 1 : given an initial interview , education , and a final interview ; 2 . Group 2 : given an initial and final interview ; and 3 . Group 3 : given one interview only . Psychological outcomes were assessed using Hospital Anxiety and Depression Scale ( HAD ) and Positive Well-Being Scale ( PWB ) scores . RESULTS Sixty-nine per cent ( 105/152 ) of eligible offspring participated . Ninety-one per cent ( 96/152 ) completed the study . Comparing first and final interviews , in Group 1 , significantly fewer responders at final interview ( after education ) thought that their risk of developing diabetes was ' low ' ( 65 % versus 41 % , P = 0.027 ) , while in Group 2 , there was no significant change in risk perception ( P = 0.13 ) . Significantly fewer people in the educated group ( Group 1 , final interview ) than in the control group ( Group 3 ) thought their risk of developing diabetes was ' low ' ( 41 % versus 77 % , P = 0.002 ) . Risk education did not affect total HAD scores or PWB scores significantly . CONCLUSION Educating offspring of people with type 2 diabetes in this way about their risk of diabetes and possible preventive strategies increases their perception of personal risk but does not cause psychological harm Primary care practitioners need to be supported by specialist genetics services to enable them to cope effectively with the exp and ing relevance of genetics to their patients . Genetic counselors could be effective in such a role . This exploratory project set out to improve the Primary –Tertiary interface through piloting such a service to general practice for 1 year . Tailored genetic educational outreach was delivered by a genetic counselor to ten r and omly selected general practice s in central Engl and for 12 months . A range of services were provided to the practice s these included facilitated genetic up date sessions , a responsive advice service and referral guidelines . The service was evaluated through pre and post intervention question naires and via seven semi-structured interviews . This article presents a description of the development and delivery of this service and also reports on the experiences of a sample of the participants . Participants reported positive attitudes to the service and said that they had gained knowledge and confidence , as well as recognized limitations and gaps in their current knowledge . The consistent link with a specialist genetics service provided by a genetic counselor had a positive impact during the project and participants have continued to utilize the genetic counselor for advice and support with genetic patient issues since the project was completed . This is the first example of this model of service provision . Further research , utilizing a larger sample and other measures of behavioral change needs to be carried out to assess whether this model should be adopted on a wider basis AIM This paper reports a pilot study to test the feasibility of providing genetic nurse counsellor clinics in primary care in the United Kingdom , to develop a question naire to evaluate patients ' satisfaction with their genetics appointments , and to establish patient and provider costs . BACKGROUND Genetic counsellors are healthcare professionals with experience in medical genetics and counselling and often have a professional background in nursing , science , genetics , psychology , or public health and work as members of multidisciplinary teams . Professional genetic counsellor accreditation is possible in the United Kingdom , United States of America , Australia and Canada . Increasing referrals to specialist genetics services have precipitated a review of models of service delivery in the United Kingdom . METHODS A r and om half of 74 general practice s in three primary care trusts were selected for the study , and the patients registered with these practice s and referred to the clinical genetics service , were offered an appointment in primary care with a genetic nurse counsellor . A clinic follow-up postal question naire was developed . RESULTS Between July 2002 and May 2003 , 64 appointments were offered to patients referred and registered with the selected general practice s , 45 ( 79 % ) patients attended their appointment and 34 ( 77 % ) returned their follow-up question naire . Total mean satisfaction score was high and patients were most satisfied with the information and affective domains of the appointment . Those referred with a family history of cancer were more satisfied than those referred with a non-cancer diagnosis . Forty-eight per cent of patients seen by the genetic nurse counsellor did not need to attend a further appointment with a doctor in secondary care . Patients were satisfied with the travel time and distance to clinic and patient clinic costs were low . CONCLUSION Patients do attend genetic nurse counsellor clinics in primary care , and are satisfied with the new location . A large cluster r and omized controlled trial is now being conducted to obtain a controlled comparison of clinic attendance rates and patients ' satisfaction with clinics in primary vs. secondary care setting |
12,440 | 30,032,399 | All three modes of exercise intervention showed a significant effect on quality of life between groups .
Conclusions Exercise is a safe and effective method of improving the quality of life in patients with breast cancer .
In particular , combined training was associated with a significant improvement in quality of life . | Purpose The purpose of this study was to conduct a systematic review to assess the effect of exercise on the quality of life among people with breast cancer . | Goals of workOur aim was to compare the effects of l and versus water multimodal exercise programs on body composition and breast cancer-specific quality of life in breast cancer survivors . Patients and methods Ninety-eight breast cancer survivors were assigned to three groups : control , l and exercise , and water exercise . Both exercise groups participated in an 8-week multimodal program . Adiposity was measured by anthropometry ( body mass index , waist circumference ) and bioelectrical impedance ( body fat and muscle lean body mass ) . Incidence of clinical ly significant secondary lymphedema was also assessed . Finally , specific quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life BR-23.Main Results Using ANCOVA , significant group × time interactions for body fat percentage ( F = 3.376 ; P = 0.011 ) and lean body mass ( F = 3.566 ; P = 0.008 ) were found . Breast cancer survivors in the l and exercise group exhibited a greater decrease in percentage of body fat than those in the water exercise ( P < 0.001 ) and control ( P = 0.002 ) groups . The ANCOVA revealed a significant group × time interaction for waist circumference ( F = 4.553 ; P = 0.002 ) : breast cancer survivors in the control group showed a greater waist circumference when compared to water ( P = 0.003 ) and l and ( P < 0.001 ) exercise groups . A significant group × time interaction was also found for breast symptoms ( F = 9.048 ; P < 0.001 ) : participants in the water exercise group experienced a greater decrease of breast symptoms than those in the l and exercise ( P < 0.01 ) and control ( P < 0.05 ) groups . Conclusion L and exercise produced a greater decrease in body fat and an increase in lean body mass , whereas water exercise was better for improving breast symptoms Few r and omized controlled trials have examined the effects of combined aerobic and resistance training in breast cancer survivors soon after completing adjuvant therapy . Breast cancer survivors ( N = 58 ) within 2 years of completing adjuvant therapy were r and omly assigned to an immediate exercise group ( IEG ; n = 29 ) or a delayed exercise group ( DEG ; n = 29 ) . The IEG completed 12 weeks of supervised aerobic and resistance exercise , three times per week . The DEG completed the program during the next 12 weeks . Participants completed patient-rated outcomes at baseline , 6 , 12 , 18 and 24 weeks . The primary endpoint was overall quality of life ( QoL ) measured by the Functional Assessment of Cancer Therapy-Breast scale . Secondary endpoints were fatigue , social physique anxiety , and physical fitness . Follow-up data was obtained on 97 % of participants and exercise adherence was 61.3 % . Repeated measures analyses of variance revealed a significant group by time interaction for overall QoL ( P < 0.001 ) . Specifically , QoL increased in the IEG from baseline to 12 weeks by 20.8 points compared to a decrease in the DEG of 5.3 points ( mean group difference = 26.1 ; 95 % CI = 18.3–32.7 ; P < 0.001 ) . From 12 to 24 weeks , QoL increased in the DEG by 29.5 points compared to an increase of 6.5 points in the IEG ( mean group difference = 23.0 ; 95 % CI = 16.3–29.1 ; P < 0.001 ) . Similar results were obtained for the secondary endpoints . Combined aerobic and resistance exercise soon after the completion of breast cancer therapy produces large and rapid improvements in health-related outcomes This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer The aim of this study was to determine whether an exercise program , commencing 4–6 weeks post-operatively , reduces upper limb impairments in women treated for early breast cancer . Women ( n = 160 ) were r and omized to either an 8-week exercise program ( n = 81 ) or to a control group ( n = 79 ) following stratification for axillary surgery . The exercise program comprised a weekly session and home program of passive stretching and progressive resistance training for shoulder muscles . The control group attended fortnightly assessment s but no exercises were provided . The primary outcome was self-reported arm symptoms derived from the EORTC breast cancer-specific question naire ( BR23 ) , scored out of 100 with a low score indicative of fewer symptoms . The secondary outcomes included physical measures of shoulder range of motion , strength , and swelling ( i.e. , lymphedema ) . Women were assessed immediately following the intervention and at 6 months post-intervention . The change in symptoms from baseline was not significantly different between groups immediately following the intervention or at 6 m post-intervention . The between group difference immediately following the intervention was 4 ( 95 % CI −1 to 9 ) and 6 months post-intervention was 4 ( −2 to 10 ) . However , the change in range of motion for flexion and abduction was significantly greater in the exercise group immediately following the intervention , as was change in shoulder abductor strength . In conclusion , a supervised exercise program provided some , albeit small , additional benefit at 6 months post-intervention to women who had been provided with written information and reminders to use their arm . Both the groups reported few impairments including swelling immediately following the intervention and 6 months post-intervention . Notably , resistance training in the post-operative period did not precipitate lymphedema OBJECTIVES This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer out patients undergoing adjuvant radiotherapy at a cancer centre . METHODS Eighty-eight stage II and III breast cancer out patients were r and omly assigned to receive yoga ( n = 44 ) or brief supportive therapy ( n = 44 ) prior to their radiotherapy treatment . Intervention consisted of yoga sessions lasting 60 min daily while the control group was imparted supportive therapy once in 10 days . Assessment s included European Organization for Research in the Treatment of Cancer- Quality of Life ( EORTCQoL C30 ) functional scales and Positive and Negative Affect Schedule ( PANAS ) . Assessment s were done at baseline and after 6 weeks of radiotherapy treatment . RESULTS An intention to treat GLM repeated measures ANOVA showed significant difference across groups over time for positive affect , negative affect and emotional function and social function . There was significant improvement in positive affect ( ES = 0.59 , p = 0.007 , 95%CI 1.25 to 7.8 ) , emotional function ( ES = 0.71 , p = 0.001 , 95%CI 6.45 to 25.33 ) and cognitive function ( ES = 0.48 , p = 0.03 , 95%CI 1.2 to 18.5 ) , and decrease in negative affect ( ES = 0.84 , p<0.001 , 95%CI -13.4 to -4.4 ) in the yoga group as compared to controls . There was a significant positive correlation between positive affect with role function , social function and global quality of life . There was a significant negative correlation between negative affect with physical function , role function , emotional function and social function . CONCLUSION The results suggest a possible role for yoga to improve quality of life and affect in breast cancer out patients BACKGROUND Exercise has been reported to decrease cancer-related fatigue and to increase quality of life ( QoL ) in various breast cancer ( BC ) population s. However , studies investigating exercise during radiotherapy or resistance training are scarce . We conducted a r and omized , controlled trial ( BEST study ) to assess the efficacy of 12-week resistance training on fatigue beyond possible psychosocial effects of a group-based intervention . PATIENTS AND METHODS One hundred sixty patients with BC stage 0-III were r and omly assigned to a 12-week progressive resistance training ( 2 times/week ) or a 12-week relaxation control ( RC , 2 times/week ) . Both interventions were group-based . The primary end point fatigue was assessed with a 20-item multidimensional question naire , QoL with EORTC question naires . Statistical analyses were based on analysis of covariance models for the individual changes from baseline to week 13 . RESULTS Adherence to the intervention program as well as the completion rate ( 97 % ) for the primary outcome variable fatigue was high . In intention-to-treat analyses for the N = 155 patients , significant between-group mean differences ( MD ) favoring the exercise group ( EX ) were observed for general fatigue ( P = 0.044 ) , especially for the subscale physical fatigue [ MD = -0.8 ; 95 % confidence interval -1.5 to -0.2 , P = 0.013 ] , but not for affective ( P = 0.91 ) or cognitive fatigue ( P = 0.65 ) . For QoL , significantly larger improvements regarding the role function ( P = 0.035 ) and pain ( P = 0.040 ) were noted among exercisers compared with RCs . Future perspective improved significantly stronger in the RC group compared with the EX group ( P = 0.047 ) . CONCLUSIONS The 12-week resistance training program was a safe , feasible and efficacious strategy to improve cancer-related fatigue and components of QoL in BC patients during adjuvant radiotherapy . As exercise was compared with another group-based intervention , results indicate that resistance training effects on fatigue and QoL go beyond psychosocial benefits , and that the clinical ly relevant overall benefit of resistance exercise compared with usual care can be assumed to be higher . TRIAL REGISTRATION Clinical Trials.gov NCT01468766 Background Secondary arm lymphoedema continues to affect at least 20 % of women after treatment for breast cancer requiring lifelong professional treatment and self-management . The holistic practice of yoga may offer benefits as an adjunct self-management option . The aim of this small pilot trial was to gain preliminary data to determine the effect of yoga on women with stage one breast cancer-related lymphoedema ( BCRL ) . This paper reports the results for the primary and secondary outcomes . Methods Participants were r and omised , after baseline testing , to receive either an 8-week yoga intervention ( n = 15 ) , consisting of a weekly 90-minute teacher-led class and a 40-minute daily session delivered by DVD , or to a usual care wait-listed control group ( n = 13 ) . Primary outcome measures were : arm volume of lymphoedema measured by circumference and extra-cellular fluid measured by bioimpedance spectroscopy . Secondary outcome measures were : tissue in duration measured by tonometry ; levels of sensations , pain , fatigue , and their limiting effects all measured by a visual analogue scale ( VAS ) and quality of life based on the Lymphoedema Quality of Life Tool ( LYMQOL ) . Measurements were conducted at baseline , week 8 ( post-intervention ) and week 12 ( four weeks after cessation of the intervention ) . Results At week 8 , the intervention group had a greater decrease in tissue in duration of the affected upper arm compared to the control group ( p = 0.050 ) , as well as a greater reduction in the symptom sub-scale for QOL ( p = 0.038 ) . There was no difference in arm volume of lymphoedema or extra-cellular fluid between groups at week 8 ; however , at week 12 , arm volume increased more for the intervention group than the control group ( p = 0.032 ) . Conclusions An 8-week yoga intervention reduced tissue in duration of the affected upper arm and decreased the QOL sub-scale of symptoms . Arm volume of lymphoedema and extra-cellular fluid did not increase . These benefits did not last on cessation of the intervention when arm volume of lymphoedema increased . Further research trials with a longer duration , higher levels of lymphoedema and larger numbers are warranted before definitive conclusions can be made Exercise for Health was a r and omized , controlled trial design ed to evaluate two modes of delivering ( face-to-face [ FtF ] and over-the-telephone [ Tel ] ) an 8-month translational exercise intervention , commencing 6-weeks post-breast cancer surgery ( PS ) . Outcomes included quality of life ( QoL ) , function ( fitness and upper body ) and treatment-related side effects ( fatigue , lymphoedema , body mass index , menopausal symptoms , anxiety , depression and pain ) . Generalised estimating equation modelling determined time ( baseline [ 5 weeks PS ] , mid-intervention [ 6 months PS ] , post-intervention [ 12 months PS ] ) , group ( FtF , Tel , Usual Care [ UC ] ) and time-by-group effects . 194 women representative of the breast cancer population were r and omised to the FtF ( n = 67 ) , Tel ( n = 67 ) and UC ( n = 60 ) groups . There were significant ( p < 0.05 ) interaction effects on QoL , fitness and fatigue with differences being observed between the treatment groups and the UC group . Trends observed for the treatment groups were similar . The treatment groups reported improved QoL , fitness and fatigue over time and changes observed between baseline and post-intervention were clinical ly relevant . In contrast , the UC group experienced no change , or worsening QoL , fitness and fatigue , mid-intervention . Although improvements in the UC group occurred by 12-months post-surgery , the change did not meet the clinical ly relevant threshold . There were no differences in other treatment-related side effects between groups . This translational intervention trial , delivered either FtF or Tel , supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment OBJECTIVE To determine the effect of exercise on quality of life in ( a ) a r and omized controlled trial of exercise among recently diagnosed breast cancer survivors undergoing adjuvant therapy and ( b ) a similar trial among post-treatment survivors . METHODS Fifty newly diagnosed breast cancer survivors were recruited through a hospital-based tumor registry and r and omized to a 6-month , home-based exercise program ( n=25 ) or a usual care group ( n=25 ) . In a separate trial , 75 post-treatment survivors were r and omized to a 6-month , supervised exercise intervention ( n=37 ) or to usual care ( n=38 ) . Participants in both studies completed measures of happiness , depressive symptoms , anxiety , stress , self-esteem , and quality of life at baseline and 6 months . RESULTS Forty-five participants completed the trial for newly diagnosed survivors and 67 completed the trial for post-treatment survivors . Good adherence was observed in both studies . Baseline quality of life was similar for both studies on most measures . Exercise was not associated with quality of life benefits in the full sample of either study ; however exercise was associated with improved social functioning among post-treatment survivors who reported low social functioning at baseline ( p<0.05 ) . CONCLUSIONS Exercise did not affect quality of life in either recently diagnosed or post-treatment breast cancer survivors ; however this may be due in part to relatively high baseline functioning among participants in both studies . Strategies for future research include limiting enrollment to survivors who report reduced quality of life on screening question naires and targeting survivor subgroups known to be at particular risk for quality of life impairment Background To improve adherence to physical activity ( PA ) , behavioural support in the form of behavioural change counselling may be necessary . However , limited evidence of the effectiveness of home-based PA combined with counselling in breast cancer patients exists . The aim of this current r and omised controlled trial with a parallel group design was to evaluate the effectiveness of a home-based PA intervention on PA levels , anthropometric measures , health-related quality of life ( HRQoL ) , and blood biomarkers in breast cancer survivors . Methods Eighty post-adjuvant therapy invasive breast cancer patients ( age = 53.6 ± 9.4 years ; height = 161.2 ± 6.8 cm ; mass = 68.7 ± 10.5 kg ) were r and omly allocated to a 6-month home-based PA intervention or usual care . The intervention group received face-to-face and telephone PA counselling aim ed at encouraging the achievement of current recommended PA guidelines . All patients were evaluated for our primary outcome , PA ( International PA Question naire ) and secondary outcomes , mass , BMI , body fat % , HRQoL ( Functional assessment of Cancer Therapy-Breast ) , insulin resistance , triglycerides ( TG ) and total ( TC ) , high-density lipoprotein ( HDL-C ) and low-density lipoprotein ( LDL-C ) cholesterol were assessed at baseline and at 6-months . Results On the basis of linear mixed-model analyses adjusted for baseline values performed on 40 patients in each group , total , leisure and vigorous PA significantly increased from baseline to post-intervention in the intervention compared to usual care ( between-group differences , 578.5 MET-min∙wk−1 , p = .024 , 382.2 MET-min∙wk−1 , p = .010 , and 264.1 MET-min∙wk−1 , p = .007 , respectively ) . Both body mass and BMI decreased significantly in the intervention compared to usual care ( between-group differences , −1.6 kg , p = .040 , and −.6 kg/m2 , p = .020 , respectively ) . Of the HRQoL variables , FACT-Breast , Trial Outcome Index , functional wellbeing , and breast cancer subscale improved significantly in the PA group compared to the usual care group ( between-group differences , 5.1 , p = .024 ; 5.6 , p = .001 ; 1.9 p = .025 ; and 2.8 , p = .007 , respectively ) . Finally , TC and LDL-C was significantly reduced in the PA group compared to the usual care group ( between-group differences , −.38 mmol∙L−1 , p = .001 ; and −.3 mmol∙L−1 , p = .023 , respectively ) . Conclusions We found that home-based PA result ed in significant albeit small to moderate improvements in self-reported PA , mass , BMI , breast cancer specific HRQoL , and TC and LDL-C compared with usual care . Clinical Trials.gov identifierNCT02408107 ( March 25 , 2015 PURPOSE Interventions to increase physical activity among breast cancer survivors are needed to improve health and quality of life and possibly to reduce the risk of disease recurrence and early mortality . Therefore , we report the feasibility and preliminary outcomes of a pilot r and omized trial design ed to increase physical activity in sedentary breast cancer survivors receiving hormone therapy . METHODS Forty-one sedentary women on estrogen receptor modulators or aromatase inhibitors for stage I , II , or IIIA breast cancer were r and omly assigned to receive a 12-wk multidisciplinary physical activity behavior change intervention or usual care . RESULTS Recruitment was 34 % , intervention adherence was 99 % , and complete follow-up data were obtained on 93 % . Most participants ( 93 % ) were white with mean age of 53 + /- 9 yr . Differences favoring the intervention group were noted for accelerometer physical activity counts ( mean difference = 72,103 ; 95 % confidence interval ( CI ) = 25,383 - 119,000 ; effect size ( d ) = 1.02 ; P = 0.004 ) , aerobic fitness ( mean difference = 2.9 ; 95 % CI = -0.1 to 5.8 ; d = 0.64 ; P = 0.058 ) , back/leg muscle strength ( mean difference = 12.3 ; 95 % CI = 0.4 - 15.9 ; d = 0.81 ; P = 0.017 ) , waist-to-hip ratio ( mean difference = -0.05 ; 95 % CI = -0.01 to -0.08 ; d = -0.77 ; P = 0.018 ) , and social well-being ( mean difference = 2.0 ; 95 % CI = 0.3 - 3.8 ; d = 0.76 ; P = 0.03 ) . However , the intervention group also reported a greater increase in joint stiffness ( mean difference = 1.1 ; 95 % CI = 0.1 - 2.2 ; d = 0.70 ; P = 0.04 ) . CONCLUSIONS A behavior change intervention for breast cancer survivors based on the social cognitive theory is feasible and results in potentially meaningful improvements in physical activity and selected health outcomes . Confirmation in a larger study is warranted Objectives To determine functional and psychological benefits of a 12 week supervised group exercise programme during treatment for early stage breast cancer , with six month follow-up . Design Pragmatic r and omised controlled prospect i ve open trial . Setting Three National Health Service oncology clinics in Scotl and and community exercise facilities . Participants 203 women entered the study ; 177 completed the six month follow-up . Interventions Supervised 12 week group exercise programme in addition to usual care , compared with usual care . Main outcome measures Functional assessment of cancer therapy ( FACT ) question naire , Beck depression inventory , positive and negative affect scale , body mass index , seven day recall of physical activity , 12 minute walk test , and assessment of shoulder mobility . Results Mixed effects models with adjustment for baseline values , study site , treatment at baseline , and age gave intervention effect estimates ( intervention minus control ) at 12 weeks of 129 ( 95 % confidence interval 83 to 176 ) for metres walked in 12 minutes , 182 ( 75 to 289 ) for minutes of moderate intensity activity reported in a week , 2.6 ( 1.6 to 3.7 ) for shoulder mobility , 2.5 ( 1.0 to 3.9 ) for breast cancer specific subscale of quality of life , and 4.0 ( 1.8 to 6.3 ) for positive mood . No significant effect was seen for general quality of life ( FACT-G ) , which was the primary outcome . At the six month follow-up , most of these effects were maintained and an intervention effect for breast cancer specific quality of life emerged . No adverse effects were noted . Conclusion Supervised group exercise provided functional and psychological benefit after a 12 week intervention and six months later . Clinicians should encourage activity for their patients . Policy makers should consider the inclusion of exercise opportunities in cancer rehabilitation services . Trial registration Current controlled trials IS RCT N12587864 PURPOSE To evaluate yoga 's impact on inflammation , mood , and fatigue . PATIENTS AND METHODS A r and omized controlled 3-month trial was conducted with two post-treatment assessment s of 200 breast cancer survivors assigned to either 12 weeks of 90-minute twice per week hatha yoga classes or a wait-list control . The main outcome measures were lipopolysaccharide-stimulated production of proinflammatory cytokines interleukin-6 ( IL-6 ) , tumor necrosis factor alpha ( TNF-α ) , and interleukin-1β ( IL-1β ) , and scores on the Multidimensional Fatigue Symptom Inventory-Short Form ( MFSI-SF ) , the vitality scale from the Medical Outcomes Study 36-item Short Form ( SF-36 ) , and the Center for Epidemiological Studies -Depression ( CES-D ) scale . RESULTS Immediately post-treatment , fatigue was not lower ( P > .05 ) but vitality was higher ( P = .01 ) in the yoga group compared with the control group . At 3 months post-treatment , fatigue was lower in the yoga group ( P = .002 ) , vitality was higher ( P = .01 ) , and IL-6 ( P = .027 ) , TNF-α ( P = .027 ) , and IL-1β ( P = .037 ) were lower for yoga participants compared with the control group . Groups did not differ on depression at either time ( P > .2 ) . Planned secondary analyses showed that the frequency of yoga practice had stronger associations with fatigue at both post-treatment visits ( P = .019 ; P < .001 ) , as well as vitality ( P = .016 ; P = .0045 ) , but not depression ( P > .05 ) than simple group assignment ; more frequent practice produced larger changes . At 3 months post-treatment , increasing yoga practice also led to a decrease in IL-6 ( P = .01 ) and IL-1β ( P = .03 ) production but not in TNF-α production ( P > .05 ) . CONCLUSION Chronic inflammation may fuel declines in physical function leading to frailty and disability . If yoga dampens or limits both fatigue and inflammation , then regular practice could have substantial health benefits PURPOSE To examine the effects of aerobic exercise therapy on quality of life ( QoL ) and associated outcomes in women treated for breast cancer . Evidence suggests that exercise may be beneficial , but no trial has included an exercise-placebo and a usual-care group to control for the attention effects that might be associated with aerobic exercise interventions in cancer patients . PATIENTS AND METHODS A total of 108 women who had been treated for breast cancer 12 to 36 months previously were r and omly assigned to supervised aerobic exercise therapy ( n = 34 ) , exercise-placebo ( body conditioning ; n = 36 ) , or usual care ( n = 38 ) . Exercise therapy and exercise-placebo sessions took place three times per week for 8 weeks . Outcomes included QoL , depression , exercise behavior , aerobic fitness ; outcomes were assessed at baseline and at the 8- and 24-week follow-up . RESULTS Analyses of covariance revealed a significant mean difference of 9.8 units in Functional Assessment of Cancer Therapy-General ( primary outcome ) favoring aerobic exercise therapy at 8 weeks , relative to usual care . Significant differences that favored aerobic exercise therapy relative to usual care were recorded for Functional Assessment of Cancer Therapy-Breast , social/family well-being , functional well-being , and breast cancer subscale scores at 8-week follow-up . Psychological health outcomes improved modestly for both intervention groups ; these improvements were sustained for several end points . CONCLUSION Exercise therapy had large , clinical ly meaningful , short-term beneficial effects on QoL in women treated for breast cancer ; this finding can not be attributable to attention , given that the exercise-placebo group did not report similar effects relative to usual care PURPOSE To determine the effects of exercise training on cardiopulmonary function and quality of life ( QOL ) in postmenopausal breast cancer survivors who had completed surgery , radiotherapy , and /or chemotherapy with or without current hormone therapy use . METHODS Fifty-three postmenopausal breast cancer survivors were r and omly assigned to an exercise ( n = 25 ) or control ( n = 28 ) group . The exercise group trained on cycle ergometers three times per week for 15 weeks at a power output that elicited the ventilatory equivalent for carbon dioxide . The control group did not train . The primary outcomes were changes in peak oxygen consumption and overall QOL from baseline to postintervention . Peak oxygen consumption was assessed by a grade d exercise test using gas exchange analysis . Overall QOL was assessed by the Functional Assessment of Cancer Therapy-Breast scale . RESULTS Fifty-two participants completed the trial . The exercise group completed 98.4 % of the exercise sessions . Baseline values for peak oxygen consumption ( P = .254 ) and overall QOL ( P = .286 ) did not differ between groups . Peak oxygen consumption increased by 0.24 L/min in the exercise group , whereas it decreased by 0.05 L/min in the control group ( mean difference , 0.29 L/min ; 95 % confidence interval [ CI ] , 0.18 to 0.40 ; P < .001 ) . Overall QOL increased by 9.1 points in the exercise group compared with 0.3 points in the control group ( mean difference , 8.8 points ; 95 % CI , 3.6 to 14.0 ; P = .001 ) . Pearson correlations indicated that change in peak oxygen consumption correlated with change in overall QOL ( r = 0.45 ; P < .01 ) . CONCLUSION Exercise training had beneficial effects on cardiopulmonary function and QOL in postmenopausal breast cancer survivors The aim of this study was to explore the effects of exercise on angiogenesis and apoptosis-related molecules , quality of life , fatigue and depression in patients who completed breast cancer treatment . Sixty breast cancer patients were r and omised into three groups , as supervised exercise group , home exercise group and education group . Angiogenesis and apoptosis-related cytokine levels and quality of life ( EORTC QOL-C30 : European Organisation for Research and Treatment of Cancer Quality of Life C30 ) , fatigue ( Brief Fatigue Inventory ) and depression ( BDI : Beck Depression Inventory ) scores were compared before and after a 12-week exercise programme . After the exercise programme , statistically significant decreases were found in interleukin-8 and neutrophil activating protein-78 levels in the home exercise group ( P < 0.05 ) . The education group showed a statistically significant increase in monocyte chemoattractant protein-1 level ( P < 0.05 ) . Functional score and global health score of EORTC QOL-C30 in the supervised exercise group and functional score of EORTC QOL-C30 in the home exercise group increased significantly after exercise programme ( P < 0.05 ) . BDI score was significantly lower in the supervised exercise group after the exercise programme ( P < 0.05 ) . Changes in angiogenesis and apoptosis-related molecules in the study groups suggest a possible effect of exercise on these parameters . Exercise programmes are safe and effective on quality of life and depression in breast cancer patients whose treatments are complete PURPOSE Breast cancer chemotherapy may cause unfavorable changes in physical functioning , body composition , psychosocial functioning , and quality of life ( QOL ) . We evaluated the relative merits of aerobic and resistance exercise in blunting these effects . PATIENTS AND METHODS We conducted a multicenter r and omized controlled trial in Canada between 2003 and 2005 that r and omly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care ( n = 82 ) , supervised resistance exercise ( n = 82 ) , or supervised aerobic exercise ( n = 78 ) for the duration of their chemotherapy ( median , 17 weeks ; 95 % CI , 9 to 24 weeks ) . Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy-Anemia scale . Secondary end points were fatigue , psychosocial functioning , physical fitness , body composition , chemotherapy completion rate , and lymphedema . RESULTS The follow-up assessment rate for our primary end point was 92.1 % , and adherence to the supervised exercise was 70.2 % . Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem ( P = .015 ) , aerobic fitness ( P = .006 ) , and percent body fat ( adjusted P = .076 ) . Resistance exercise was superior to usual care for improving self-esteem ( P = .018 ) , muscular strength ( P < .001 ) , lean body mass ( P = .015 ) , and chemotherapy completion rate ( P = .033 ) . Changes in cancer-specific QOL , fatigue , depression , and anxiety favored the exercise groups but did not reach statistical significance . Exercise did not cause lymphedema or adverse events . CONCLUSION Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy , but they did improve self-esteem , physical fitness , body composition , and chemotherapy completion rate without causing lymphedema or significant adverse events Purpose This study examines the effects of a rehabilitation program on quality of life ( QoL ) , cardiopulmonary function , and fatigue in breast cancer patients . The program included aerobic exercises as well as stretching and strengthening exercises . Methods Breast cancer patients ( n=62 ) who had completed chemotherapy were r and omly assigned to an early exercise group ( EEG ; n=32 ) or a delayed exercise group ( DEG ; n=30 ) . The EEG underwent 4 weeks of a multimodal rehabilitation program for 80 min/day , 5 times/wk for 4 weeks . The DEG completed the same program during the next 4 weeks . The European Organization for Research and Treatment of Cancer-Core Quality of Life Question naire ( EORTC QLQ-C30 ) , EORTC Breast Cancer-Specific Quality of Life Question naire ( EORTC QLQ-BR23 ) , predicted maximal volume of oxygen consumption ( VO2max ) , and fatigue severity scale ( FSS ) were used for assessment at baseline , and at 2 , 4 , 6 , and 8 weeks . Results After 8 weeks , statistically significant differences were apparent in global health , physical , role , and emotional functions , and cancer-related symptoms such as fatigue and pain , nausea , and dyspnea on the EORTC QLQ-C30 ; cancer-related symptoms involving the arm and breast on the EORTC QLQ-BR23 ; the predicted VO2max ; muscular strength ; and FSS ( p<0.050 ) , according to time , between the two groups . Conclusion The results of our study suggest that a supervised multimodal rehabilitation program may improve the physical symptoms , QoL , and fatigue in patients with breast cancer Background : The women with breast cancer experience high rates of morbidity due to different treatments . The objective of this study was to evaluate the role of aerobic exercise in the quality of life ( QoL ) among women suffering from breast cancer in Hamadan , western Iran . Method : Participants who had consummated the eligibility criteria were r and omly assigned in exercise group ( n=30 ) and control group ( n=30 ) . Written informed consent was obtained from all participants . The mean age was 42.70 ±9.6 and 43.50 ±8.60 yr old in exercise and control groups , respectively . The quality of life was assessed by two widely used st and ard question naires ( EORTC QLQ-C30 and EORTC QLQ-BR23 ) . The exercise group received supervised exercise 2 days per week for 10 weeks . Through two stages ( before and after intervention ) these groups were evaluated . Analyzing the data was performed by SPSS/20.0 , using t-test , chi-squared and ANCOVA . P<0.05 was regarded as significant level . Results : The global health status QoL , based on EORTC QLQ-C30 , developed significantly in the exercise group ( 48.76±24.96 vs. 81.79±16.34 ) in comparison with the controls ( 47.75 ±15.73 vs. 52.88 ±14.51 ) ( P<0.001 ) . The exercise intervention was associated with substantial development in total score of functions and symptoms of QoL using EORTC QLQ-BR23 ( P<0.001 ) . Conclusions : The statistically and clinical ly crucial developments were indicated in functions and symptoms of QoL in response to exercise in breast cancer women Goals Health-related quality of life ( HRQL ) and self-esteem are often diminished among women diagnosed and treated for breast cancer . Tai Chi is a moderate form of exercise that may be an effective therapy for improving HRQL and self-esteem among these women . We sought to compare the efficacy of Tai Chi Chuan ( TCC ) and psychosocial support ( PST ) for improving HRQL and self-esteem among breast cancer survivors . Patients and methods A group of 21 women diagnosed with breast cancer , who had completed treatment within the last 30 months were r and omized to receive 12 weeks of TCC or PST . Participants in both groups met three times a week for 60 minutes . HRQL and self-esteem were assessed at baseline , 6 weeks , and 12 weeks . Results The TCC group demonstrated significant improvements in HRQL , while the PST group reported declines in HRQL , with the differences between the two groups approaching significance at week 12 . Additionally , the TCC group exhibited improvements in self-esteem , while the PST group reported declines in self-esteem , with the differences between groups reaching statistical significance at week 12 . These findings , coupled with a visual inspection of the raw change scores , support the plausibility of a dose-response relationship concerning Tai Chi . Conclusions In this pilot investigation , the TCC group exhibited improvements in HRQL and self-esteem from baseline to 6 and 12 weeks , while the support group exhibited declines . R and omized , controlled clinical trials with larger sample sizes are needed A pilot research study was conducted at 2 cancer centers in Connecticut to determine the effect of a dance and movement program on quality of life and shoulder function in breast cancer survivors treated within the prior 5 years . Thirty-five women completed the trial that included a 12-week intervention , using The Lebed Method , Focus on Healing Through Movement and Dance . The study design was a r and omized control trial with a wait list control group crossover to active treatment in weeks 13 to 25 , with the treatment group receiving the program in weeks 1 to 12 , and no program in weeks 13 to 25 . Outcome measures were the Breast Cancer Quality of Life ( FACT-B ) , Shoulder range of motion ( ROM ) , and Body Image Scale . FACT-B significantly improved in the intervention group at 13 weeks from 102.0 ± 15.8 to 116.7 ± 16.9 , compared to the wait list group 108.1 ± 16.4 to 107.1 ± 21.3 ( time × group effect , P = .008 ) . During the crossover phase , the FACT-B score increased in the wait list group and was stable in the treatment group . The overall effect of the training at 26 weeks was significant ( time effect , P = .03 ) , and the order of training was also significant ( P = .015 ) . Shoulder ROM increased in both groups at 13 weeks —15 ° and 8 ° in the intervention and wait list groups ( Time effect , P = .03 ; time × group , P = .58 ) . Body Image improved similarly in both groups at 13 weeks ( time effect , P = .001 ; time × group , P = .25 ) , and at 26 weeks . There was no significant effect of the order of training for these outcome measures . A dance movement program that addressed the physical and emotional needs of women following treatment for breast cancer substantially improved a breast cancer – specific quality -of-life measure . Larger studies are justified to determine the acceptability of this therapy as part of the continuum of care for breast cancer survivors Purpose To obtain estimates of time to recruit the study sample , retention , facility-based class attendance and home practice for a study of yoga in breast cancer survivors , and its efficacy on fatigue , quality of life ( QOL ) , and weight change . Methods Sixty-three post-treatment stages 0–III borderline overweight and obese ( body mass index ≥24 kg/m2 ) breast cancer survivors were r and omly assigned to a 6-month , facility- and home-based viniyoga intervention ( n = 32 ) or a waitlist control group ( n = 31 ) . The yoga goal was five practice s per week . Primary outcome measures were changes in QOL , fatigue , and weight from baseline to 6 months . Secondary outcomes included changes in waist and hip circumference . Results It took 12 months to complete recruitment . Participants attended a mean of 19.6 classes and practice d at home a mean of 55.8 times during the 6-month period . At follow-up , 90 % of participants completed question naires and 87 % completed anthropometric measurements . QOL and fatigue improved to a greater extent among women in the yoga group relative to women in the control group , although no differences were statistically significant . Waist circumference decreased 3.1 cm ( 95 % CI , −5.7 and −0.4 ) more among women in the yoga compared with the control group , with no difference in weight change . Conclusions This study provides important information regarding recruitment , retention , and practice levels achieved during a 6-month , intensive yoga intervention in overweight and obese breast cancer survivors . Yoga may help decrease waist circumference and improve quality of life ; future studies are needed to confirm these results This pilot study examined whether exercise as an adjunctive rehabilitation therapy could benefit women who have early stage breast cancer and are currently receiving chemotherapy/radiotherapy . The study was design ed as a r and omised controlled trial ( RCT ) . Physical functioning , fatigue and Quality of Life ( QoL ) outcomes were evaluated pre and post a 12-week intervention . The results showed that after 12 weeks the women who participated in the exercise programme ( n = 12 ) displayed significantly higher levels of physical functioning and reported higher QoL scores than the controls ( n = 10 ) . Changes in fatigue and satisfaction with life favoured the intervention group but did not reach significance . These results are encouraging and suggest that a structured group exercise programme during adjuvant treatment is a safe , well tolerated and effective way of providing physical and psychological health benefits to women during treatment for early stage breast cancer . Since this was a pilot study the numbers did not allow appropriately powered analyses of some variables of interest and favoured relatively young and socio-economically advantaged women . Future studies need to address these issues and determine if these short-term benefits can be sustained OBJECTIVES Restorative yoga ( RY ) is a gentle type of yoga that may be beneficial for cancer patients and post-treatment survivors . Study goals were : to determine the feasibility of implementing a RY intervention for women with breast cancer ; and to examine group differences in self-reported emotional , health-related quality of life , and symptom outcomes . METHODS Women with breast cancer ( n=44 ; mean age 55.8 years ) enrolled in this study ; 34 % were actively undergoing cancer treatment . Study participants were r and omized to the intervention ( 10 weekly 75-minute RY classes ) or a waitlist control group . Participants completed question naires at Week 0 ( baseline ) and Week 10 ( immediately post-intervention for the yoga group ) . RESULTS Group differences favoring the yoga group were seen for mental health , depression , positive affect , and spirituality ( peace/meaning ) . Significant baseline*group interactions were observed for negative affect and emotional well-being . Women with higher negative affect and lower emotional well-being at baseline derived greater benefit from the yoga intervention compared to those with similar values at baseline in the control group . The yoga group demonstrated a significant within-group improvement in fatigue ; no significant difference was noted for the control group . CONCLUSIONS Although limited by sample size , these pilot data suggest potential benefit of RY on emotional outcomes and fatigue in cancer patients . This study demonstrates that a RY intervention is feasible for women with breast cancer ; implication s for study design and implementation are noted with an emphasis on program adoption and participant adherence The purpose of this r and omized control trial was to verify the effectiveness of a brief group intervention that combines stress management psycho-education and physical activity ( ie , independent variable ) intervention in reducing fatigue and improving energy level , quality of life ( mental and physical ) , fitness ( VO2submax ) , and emotional distress ( ie , dependent variables ) in breast cancer survivors . This study applied Lazarus and Folkman stress-coping theoretical framework , as well as Salmon 's unifying theory of physical activity . Eighty-seven French-speaking women who had completed their treatments for nonmetastatic breast cancer at a university hospital in Quebec City , Canada , were r and omly assigned to either the group intervention ( experimental ) or the usual-care ( control ) condition . Data were collected at baseline , postintervention , and at 3-month follow-up . The 4-week group intervention was cofacilitated by 2 nurses . Results showed that participants in the intervention group showed greater improvement in fatigue , energy level , and emotional distress at 3-month follow-up , and physical quality of life at postintervention , compared with the participants in the control group . These results suggest that a brief psycho-educational group intervention focusing on active coping strategies and physical activity is beneficial to cancer survivors after breast cancer treatments BACKGROUND Adjuvant treatment for breast cancer may result in long-lasting , adverse emotional and physical side effects , and reduce quality of life ( QOL ) . This pilot study examined the effects of a home-based walking program on QOL and fatigue in early stage breast cancer survivors and whether changes in walking behavior were associated with changes in outcomes . METHODS Participants ( n = 32 ) were r and omized to a 12-week home-based walking intervention plus brief telephone counseling ( n = 20 ) or a wait-list control group ( n = 12 ) . Self-reported fatigue , QOL , and walking were assessed at baseline and 12-weeks . Results are presented as effect sizes . RESULTS Participants in the intervention had improvements in a majority of fatigue and QOL outcomes , whereas the control group had no change or worsened in many ; effect sizes were generally in the small to medium range . Changes in fatigue/QOL outcomes were associated with changes in walking behavior , with effects generally in the small to medium range . CONCLUSION Home-based physical activity ( walking ) programs may be an appropriate avenue for alleviating the adverse side effects that often accompany adjuvant treatment for breast cancer . These programs have potential for widespread dissemination , which may have considerable impact on the quality of life of women recently completing breast cancer treatment The aim of this study was to evaluate the impact of a twice-weekly strength training intervention on perceptions of body image in 234 breast cancer survivors ( 112 with lymphedema ) who participated in the Physical Activity and Lymphedema ( PAL ) trial . The study population included two hundred and thirty-four women r and omly assigned to twice-weekly strength training or control group that completed the 32-item Body Image and Relationships Scale ( BIRS ) at baseline and 12 months . Percent change in baseline to 12-month BIRS total and subscale scores , upper and lower body strength , and general quality of life ( QOL ) were compared by intervention status . A series of multiple linear regression models including indicator variables for subgroups based on age , marital status , race , education , BMI , and strength change were used to examine differential intervention impact by subgroup . Strength and QOL variables were assessed as mediators of the intervention effect on BIRS . Results : Baseline BIRS scores were similar across intervention and lymphedema status . Significantly greater improvement in BIRS total score was observed from baseline to 12 months in treatment vs. control participants ( 12.0 vs. 2.0 % ; P < 0.0001 ) . A differential impact of the intervention on the Strength and Health subscale was observed for older women ( > 50 years old ) in the treatment group ( P = 0.03 ) . Significantly greater improvement was observed in bench and leg press among treatment group when compared to control group participants , regardless of lymphedema . Observed intervention effects were independent of observed strength and QOL changes . Twice-weekly strength training positively impacted self-perceptions of appearance , health , physical strength , sexuality , relationships , and social functioning . Evidence suggests the intervention was beneficial regardless of prior diagnosis of lymphedema . Strength and QOL improvements did not mediate the observed intervention effects Radiotherapy may lead to side effects that undermine patients ' quality of life ( QOL ) . Although mind‐body practice s like qigong appear to improve QOL in cancer survivors , little is known about their benefits for patients who are receiving radiotherapy . Thus , in the current r and omized controlled trial , the authors examined the efficacy of a qigong intervention on QOL in women with breast cancer during and after treatment PURPOSE Participating in regular physical activity is encouraged after treatment for breast cancer , with exception of those who have subsequently developed lymphedema . The purpose of this project was to investigate , in a r and omized controlled trial , the effect of participating in a supervised , mixed-type exercise program on lymphedema status among women with lymphedema after breast cancer . METHODS Women younger than 76 yr , who completed breast cancer treatment at least 6 months prior and had subsequently developed unilateral , upper-limb lymphedema , were r and omly allocated to an intervention ( n = 16 ) or control ( n = 16 ) group . The intervention group ( IG ) participated in 20 supervised , group , aerobic and resistance exercise sessions over 12 wk , whereas the control group ( CG ) was instructed to continue habitual activities . Lymphedema status was assessed by bioimpedance spectroscopy ( impedance ratio between limbs ) and perometry ( volume difference between limbs ) , and independent t-tests ( two-tailed P < 0.05 ) were used to determine statistical significance of observed changes . RESULTS Mean ratio and volume measures at baseline were similar for the IG ( 1.13 + /- 0.15 and 337 + /- 307 mL , respectively ) and the CG ( 1.13 + /- 0.19 and 377 + /- 416 mL , respectively ) , and no changes were observed over time for either group . Although no group change was observed between preintervention and 3-month follow-up for the IG ( ratio and volume change = 0.02 + /- 0.07 and 2 + /- 71 mL , respectively ) , two women in this group no longer had evidence of lymphedema by study end . Average attendance was more than 70 % of supervised sessions , there were no withdrawals , and several qualitative comments from participants support the program acceptability . CONCLUSIONS The results from this pilot study indicate that , at minimum , exercise does not exacerbate secondary lymphedema . Women with secondary lymphedema should be encouraged to be physically active , optimizing their physical and psychosocial recovery The purpose of this pilot study was to examine the effects of a combined cardiorespiratory and resistance exercise training program of short duration on the cardiorespiratory fitness , strength endurance , task specific functional muscle capacity , body composition and quality of life ( QOL ) in women breast cancer survivors . Sixteen subjects were r and omly assigned to either a training ( n = 8 ; age : 50 + /- 5 yrs ) or control non-exercising group ( n = 8 ; age : 51 + /- 10 yrs ) . The training group followed an 8-week exercise program consisting of 3 weekly sessions of 90-min duration , supervised by an experienced investigator and divided into resistance exercises and aerobic training . Before and after the intervention period , all of the subjects performed a cardiorespiratory test to measure peak oxygen uptake ( VO2peak ) , a dynamic strength endurance test ( maximum number of repetitions for chest and leg press exercise at 30 - 35 % and 100 - 110 % of body mass , respectively ) and a sit-st and test . Quality of life was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 ( EORTC-C30 ) question naire . In response to training , QOL , VO2peak ( mean 3.9 ml/kg/min ; 95 % CI , 0.93 , 6.90 ) performance in leg press ( 17.9 kg ; 95 % CI , 12.8 , 22.4 ) and sit-st and test ( - 0.67 s ; 95 % CI , - 0.52 , - 1.2 ) improved ( p < or = 0.05 ) . We observed no significant changes in the control group . Combined cardiorespiratory and resistance training , even of very brief duration , improves the QOL and the overall physical fitness of women breast cancer survivors The purpose of this study was to conduct an exploratory analysis of the START examining the effects of resistance exercise training ( RET ) and aerobic exercise training ( AET ) on sarcopenia , dynapenia , and associated quality of life ( QoL ) changes in breast cancer ( BC ) patients receiving adjuvant chemotherapy . Participants were r and omized to usual care ( UC ) ( n = 70 ) , AET ( n = 64 ) , or RET ( n = 66 ) for the duration of chemotherapy . Measures of sarcopenia [ skeletal muscle index ( SMI ) ] and dynapenia [ upper extremity ( UE ) and lower extremity ( LE ) muscle dysfunction ( MD ) ] were normalized relative to age-/sex-based clinical cut-points . QoL was assessed by the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) scales . At baseline , 25.5 % of BC patients were sarcopenic and 54.5 % were dynapenic with both conditions associated with poorer QoL. ANCOVAs showed significant differences favoring RET over UC for SMI ( 0.32 kg/m2 ; p = 0.017 ) , UE-MD ( 0.12 kg/kg ; p < 0.001 ) , and LE-MD ( 0.27 kg/kg ; p < 0.001 ) . Chi-square analyses revealed significant effects of RET , compared to UC/AET combined , on reversing sarcopenia ( p = 0.039 ) and dynapenia ( p = 0.019 ) . The reversal of sarcopenia was associated with clinical ly relevant improvements in the FACT-An ( 11.7 points [ 95 % confidence interval ( CI ) −4.2 to 27.6 ] ) , the Trial Outcome Index-Anemia ( 10.0 points [ 95 % CI −4.0 to 24.1 ] ) , and fatigue ( 5.3 points [ 95 % CI −1.5 to 12.1 ] ) . Early-stage BC patients initiating adjuvant chemotherapy have higher than expected rates of sarcopenia and dynapenia which are associated with poorer QoL. RET during adjuvant chemotherapy result ed in the reversal of both sarcopenia and dynapenia ; however , only the reversal of sarcopenia was associated with clinical ly meaningful improvements in PURPOSE Previous research incorporating yoga ( YG ) into radiotherapy ( XRT ) for women with breast cancer finds improved quality of life ( QOL ) . However , shortcomings in this research limit the findings . PATIENTS AND METHODS Patients with stages 0 to III breast cancer were recruited before starting XRT and were r and omly assigned to YG ( n = 53 ) or stretching ( ST ; n = 56 ) three times a week for 6 weeks during XRT or waitlist ( WL ; n = 54 ) control . Self-report measures of QOL ( Medical Outcomes Study 36-item short-form survey ; primary outcomes ) , fatigue , depression , and sleep quality , and five saliva sample s per day for 3 consecutive days were collected at baseline , end of treatment , and 1 , 3 , and 6 months later . RESULTS The YG group had significantly greater increases in physical component scale scores compared with the WL group at 1 and 3 months after XRT ( P = .01 and P = .01 ) . At 1 , 3 , and 6 months , the YG group had greater increases in physical functioning compared with both ST and WL groups ( P < .05 ) , with ST and WL differences at only 3 months ( P < .02 ) . The group differences were similar for general health reports . By the end of XRT , the YG and ST groups also had a reduction in fatigue ( P < .05 ) . There were no group differences for mental health and sleep quality . Cortisol slope was steepest for the YG group compared with the ST and WL groups at the end ( P = .023 and P = .008 ) and 1 month after XRT ( P = .05 and P = .04 ) . CONCLUSION YG improved QOL and physiological changes associated with XRT beyond the benefits of simple ST exercises , and these benefits appear to have long-term durability BACKGROUND Research has shown that self-directed stress management training improves mental well-being in patients undergoing chemotherapy . The present study extends this work by evaluating separate and combined effects of stress management training and home-based exercise . METHOD Following assessment of mental and physical well-being , depression , anxiety , exercise , and stress reduction activity before chemotherapy started , patients were r and omized to stress management training ( SM ) , exercise ( EX ) , combined stress management and exercise ( SMEX ) , or usual care only ( UCO ) . Outcomes were reassessed 6 and 12 weeks after chemotherapy started . Significance testing of group-by-time interactions in 286 patients who completed all assessment s was used to evaluate intervention efficacy . RESULTS Interaction effects for mental and physical well-being scores were not significant . Depression scores yielded a linear interaction comparing UCO and SMEX ( p = 0.019 ) , with decreases in SMEX but not UCO . Anxiety scores yielded a quadratic interaction comparing UCO and SMEX ( p = 0.049 ) , with trends for changes in SMEX but not UCO . Additional analyses yielded quadratic interactions for exercise activity comparing UCO and SMEX ( p = 0.022 ) , with positive changes in SMEX but not UCO , and for stress management activity comparing UCO and SM ( p < 0.001 ) and UCO and SMEX ( p = 0.013 ) , with positive changes in SM and SMEX but not UCO . CONCLUSION Only the combined intervention yielded effects on quality of life outcomes , and these were limited to anxiety and depression . These findings are consistent with evidence that only the combined intervention yielded increases in both exercise and stress management activity . Future research should investigate ways to augment this intervention to enhance its benefits OBJECTIVE This paper will report the results of a pilot test of a 6-month , 21-session intervention to increase breast cancer survivors ' physical activity by teaching them to incorporate short periods of moderate activity into their daily routines ( lifestyle intervention ) . The effect of the intervention on physical performance , quality of life , and physical activity are reported . METHODS Sixty breast cancer survivors were r and omized to either a lifestyle intervention or a st and ard care control group . Physical performance , quality of life ( Medical outcomes study short form-36 [ SF-36 ] ) , and physical activity ( 7-day recall and motivation readiness ) , were assessed at baseline and 6 months . RESULTS The lifestyle group had significantly better performance in the 6-min walk task than the controls ( p=0.005 ) at 6 months . The intervention had positive effects on the bodily pain ( p=0.020 ) and general health ( p=0.006 ) subscales from the SF-36 . The lifestyle group had a greater motivational readiness for physical activity at 6-month than st and ard care , but no significant differences were seen between the two in terms of number of minutes of moderate or more intense physical activity or number of days on which they did > or = 30 min of moderate or more intense activity . CONCLUSIONS Despite the small sample size , the lifestyle intervention showed promise for improving physical functioning and quality of life and increasing physical activity , and should be tested in a larger r and omized trial . PRACTICE IMPLICATION S If the lifestyle approach is shown to be effective in a larger trial , it represents a highly feasible intervention that it can be delivered to cancer survivors by health care institutions or community organizations without dedicated exercise facilities and equipment Question : Does exercise training improve cardiopulmonary function and quality of life in postmenopausal breast cancer survivors ? Design : R and omised controlled trial . Setting : Specialised cancer institute Patients : Postmenopausal women who met the following inclusion criteria : histology confirmed early stage breast cancer with no evidence of recurrent or progressive disease ; completed surgery , radiotherapy , and /or chemotherapy with or without current hormone therapy use ; and non-smoking status . Exclusion criteria were : cardiac disease , uncontrolled hypertension , thyroid disease , diabetes , mental illness , infection , immune or endocrine abnormality , or contraindications for exercise . Patients were r and omly allocated to an exercise ( n = 25 ) or control group ( n = 28 ) Interventions : The exercise group received exercise training on bicycle ergometers with a training intensity that corresponded to approximately 70 % to 75 % of maximal oxygen consumption . There were three sessions a week for a period of 15 weeks and the exercise intensity increased systematic ally from 15 minutes in the first three weeks to 35 minutes in the last three weeks . The control group did not exercise . Outcomes : These consisted of cardiopulmonary fitness outcomes as measured with a bicycle test , quality of life as assessed by the Functional Assessment of Cancer Therapy-Breast Scale , and body composition ( body weight , body mass index and subcutaneous sum of skinfolds , all assessed at baseline and post-intervention , ie after 15 weeks follow-up ) . Main results : The exercise group completed 98.4 % of the exercise sessions . The mean difference in peak oxygen consumption was 0.29 L/min in favour of the exercise group ( 95 % CI = 0.18 to 0.40 ; p < 0.01 ) . The mean difference in improvement in quality of life was 8.8 points , which was in favour of the exercise group ( 95 % CI = 3.6 to 14.0 ; p < 0.01 ) . No statistically significant inter-group differences were found for measures of body composition . Conclusion : Exercise training had beneficial effects on cardiopulmonary function and quality of life in postmenopausal breast cancer survivors . Abstract Background . To evaluate the safety and efficacy of moderate-to-high intensity aerobic training in breast cancer patients receiving neoadjuvant chemotherapy . Methods . Twenty patients with stage IIB – IIIC operable breast cancer were r and omly assigned to receive doxorubicin plus cyclophosphamide ( AC ) or AC in combination with aerobic training ( AC + AET ) ( n = 10/group ) for 12 weeks . The AC+ AET group performed three supervised aerobic cycle ergometry sessions per week at 60%–100 % of exercise capacity ( VO2peak ) . Safety outcomes included exercise testing as well as treatment- and exercise training-related adverse events ( AEs ) , whereas efficacy outcomes included cardiopulmonary function and patient-reported outcomes ( PROs ) as measured by a cardiopulmonary exercise test ( CPET ) and Functional Assessment of Cancer Therapy-Breast ( FACT-B ) scale . Results . Twelve non-significant ECG abnormalities and three non-life threatening events occurred during CPET procedures . One AE was reported during aerobic training . There were no significant between group differences for clinician-documented events ( e.g. pain , nausea ) or hematological parameters ( p 's > 0.05 ) . Attendance and adherence rates to aerobic training were 82 % and 66 % , respectively . Intention-to-treat analysis indicated that VO2peak increased by 2.6 ± 3.5 ml/kg/min ( + 13.3 % ) in the AC + AET group and decreased by 1.5 ± 2.2 ml/kg/min ( −8.6 % ) in the AC group ( between group difference , p = 0.001 ) . FACT-B increased 11.1 points in the AC + AET group compared to a 1.5 point decrease in the AC group ( between group difference , p = 0.685 ) . Conclusion . Moderate-to-high intensity aerobic training when conducted with one-on-one supervision is a safe adjunct therapy associated with improvements in cardiopulmonary function and select PROs during neoadjuvant chemotherapy |
12,441 | 30,570,408 | The review suggests that optimism is associated with less acute and chronic pain , especially since a higher percentage of beneficial associations was found with high study /publication quality and with the primary focus on this relationship . | Abstract A growing body of literature provides evidence of the health-promoting effects of optimism , including its protective role in acute and chronic pain .
Optimists are characterized by positive expectations concerning the future .
These positive outcome expectancies lead to more and longer goal -directed efforts and the use of approach coping strategies .
No systematic review on the effects of optimism on the experience of pain has so far been conducted . | Background Decreased pain represents a clinical ly important outcome following arthroscopic knee surgery . However , little is known about preoperative mood and attitudinal factors and their potential relationship with pain outcomes . Purpose This prospect i ve , longitudinal study investigated the influence of preoperative depression , stress , and optimism on pain severity and interference with functioning , controlling for relevant demographic and clinical factors 1 year postoperatively . Methods Participants ( N = 180 , mean age = 48.2 years ) completed scales assessing pain severity and interference both preoperatively and postoperatively . Demographics , depression , stress , optimism , and body mass index were assessed preoperatively . Physicians assessed extent of knee osteoarthritis during surgery . Results Hierarchical regression analyses controlling for relevant demographic and clinical variables revealed that optimism and stress were significant predictors of pain severity at 1 year but not pain interference . Extent of osteoarthritis predicted pain interference . Conclusions These findings support that optimism and stress are important predictors of patient-rated pain severity . They do not , however , predict the extent to which pain interferes with daily functioning Abstract Background Chronic pain is associated with emotional problems as well as difficulties in cognitive functioning . Prior experimental studies have shown that optimism , the tendency to expect that good things happen in the future , and positive emotions can counteract pain‐induced task performance deficits in healthy participants . More specifically , induced optimism was found to buffer against the negative effects of experimental pain on executive functioning . This clinical experiment examined whether this beneficial effect can be extended to a chronic pain population . Methods Patients ( N = 122 ) were r and omized to a positive psychology Internet‐based intervention ( PPI ; n = 74 ) or a waiting list control condition ( WLC ; n = 48 ) . The PPI consisted of positive psychology exercises that particularly target optimism , positive emotions and self‐compassion . Results Results demonstrated that patients in the PPI condition scored higher on happiness , optimism , positive future expectancies , positive affect , self‐compassion and ability to live a desired life despite pain , and scored lower on pain catastrophizing , depression and anxiety compared to patients in the WLC condition . However , executive task performance did not improve following completion of the PPI , compared to the WLC condition . Conclusions Despite the lack of evidence that positive emotions and optimism can improve executive task performance in chronic pain patients , this study did convincingly demonstrate that it is possible to increase positive emotions and optimism in chronic pain patients with an online positive psychology intervention . It is imperative to further explore amendable psychological factors that may reduce the negative impact of pain on executive functioning . Significance We demonstrated that an Internet‐based positive psychology intervention strengthens optimism and positive emotions in chronic pain patients . These emotional improvements are not associated with improved executive task performance . As pain itself often can not be relieved , it is imperative to have techniques to reduce the burden of living with chronic pain Objectives : To assess the contribution of important psychological re sources ( i.e. optimism , pessimism , control beliefs ) to the psychological well-being of older adults with Osteoarthritis ( OA ) ; to assess the direct and mediated association of these psychosocial re sources to outcomes ( depressive symptoms , life satisfaction , and self-esteem ) . These objectives are important because OA is a significant stressor , treatments are limited , and psychological functioning is at risk for those coping with the condition , even compared to other chronic illnesses . Method : A cross-sectional survey of 160 community-dwelling older adults with OA ( 81 % women ) . Participants were not r and omly selected , but nonetheless reflected the demographic makeup of the selection area . Results : Ordinary least squares regression analyses using the PROCESS macro revealed that optimism and pessimism were associated with higher depressive symptoms and lower self-esteem indirectly through constraints beliefs . The analysis of life satisfaction showed that optimism and pessimism were each partially mediated through mastery and constraints beliefs . Discussion : These results suggest that prior research , which has assessed these psychological re sources as having singular relationships to outcomes , may have underestimated the importance of the relationship between these variables . We discuss possible points of intervention for older adults with OA who may experience increasing constraints beliefs over time Background : Few epidemiological studies have prospect ively investigated preoperative and surgical risk factors for acute postoperative pain after surgery for breast cancer . We investigated demographic , psychological , pain-related and surgical risk factors in women undergoing resectional surgery for breast cancer . Methods : Primary outcomes were pain severity , at rest ( PAR ) and movement-evoked pain ( MEP ) , in the first postoperative week . Results : In 338 women undergoing surgery , those with chronic preoperative pain were three times more likely to report moderate to severe MEP after breast cancer surgery ( OR 3.18 , 95 % CI 1.45–6.99 ) . Increased psychological ‘ robustness ’ , a composite variable representing positive affect and dispositional optimism , was associated with lower intensity acute postoperative PAR ( OR 0.63 , 95 % CI 0.48–0.82 ) and MEP ( OR 0.71 , 95 % CI 0.54–0.93 ) . Sentinel lymph node biopsy ( SLNB ) and intraoperative nerve division were associated with reduced postoperative pain . No relationship was found between preoperative neuropathic pain and acute pain outcomes ; altered sensations and numbness postoperatively were more common after axillary sample or clearance compared with SLNB . Conclusion : Chronic preoperative pain , axillary surgery and psychological robustness significantly predicted acute pain outcomes after surgery for breast cancer . Preoperative identification and targeted intervention of subgroups at risk could enhance the recovery trajectory in cancer survivors • STUDY DESIGN : Secondary analysis of prospect ively collected data . • BACKGROUND : An abundance of evidence has highlighted the influence of pain catastrophizing and fear avoidance on clinical outcomes . Less is known about the interaction of positive psychological re sources with these pain‐associated distress factors . • OBJECTIVE : To assess whether optimism moderates the influence of pain catastrophizing and fear avoidance on 3‐month clinical outcomes in patients with shoulder pain . • METHODS : Data from 63 individuals with shoulder pain ( mean ± SD age , 38.8 ± 14.9 years ; 30 female ) were examined . Demographic , psychological , and clinical characteristics were obtained at baseline . Vali date d measures were used to assess optimism ( Life Orientation Test‐Revised ) , pain catastrophizing ( Pain Catastrophizing Scale ) , fear avoidance ( Fear‐Avoidance Beliefs Question naire physical activity subscale ) , shoulder pain intensity ( Brief Pain Inventory ) , and shoulder function ( Pennsylvania Shoulder Score function subscale ) . Shoulder pain and function were reassessed at 3 months . Regression models assessed the influence of ( 1 ) pain catastrophizing and optimism and ( 2 ) fear avoidance and optimism . The final multivariable models controlled for factors of age , sex , education , and baseline scores , and included 3‐month pain intensity and function as separate dependent variables . • RESULTS : Shoulder pain ( mean difference , ‐1.6 ; 95 % confidence interval [ CI ] : ‐2.1 , ‐1.2 ) and function ( mean difference , 2.4 ; 95 % CI : 0.3 , 4.4 ) improved over 3 months . In multivariable analyses , there was an interaction between pain catastrophizing and optimism ( & bgr ; = 0.19 ; 95 % CI : 0.02 , 0.35 ) for predicting 3‐month shoulder function ( F = 16.8 , R2 = 0.69 , P<.001 ) , but not pain ( P = .213 ) . Further examination of the interaction with the Johnson‐Neyman technique showed that higher levels of optimism lessened the influence of pain catastrophizing on function . There was no evidence of significant moderation of fear‐avoidance beliefs for 3‐month shoulder pain ( P = .090 ) or function ( P = .092 ) . • CONCLUSION : Optimism decreased the negative influence of pain catastrophizing on shoulder function , but not pain intensity . Optimism did not alter the influence of fear‐avoidance beliefs on these outcomes . • LEVEL OF EVIDENCE : Prognosis , level 2b BACKGROUND Major depression is known to be related to higher cardiovascular mortality . However , epidemiological data regarding dispositional optimism in relation to mortality are scanty . OBJECTIVE To test whether subjects who are optimistic live longer than those who are pessimistic . DESIGN Our analysis formed part of a prospect i ve population -based cohort study in the Netherl and s ( Arnhem Elderly Study ) . SETTING General community . PARTICIPANTS Elderly subjects aged 65 to 85 years ( 999 men and women ) completed the 30-item vali date d Dutch Scale of Subjective Well-being for Older Persons , with 5 subscales : health , self-respect , morale , optimism , and contacts . A total of 941 subjects ( 466 men and 475 women ) had complete dispositional optimism data , and these subjects were divided into quartiles . MAIN OUTCOME MEASURE Number of deaths during the follow-up period . RESULTS During the follow-up period of 9.1 years ( 1991 - 2001 ) , there were 397 deaths . Compared with subjects with a high level of pessimism , those reporting a high level of optimism had an age- and sex-adjusted hazard ratio of 0.55 ( 95 % confidence interval , 0.42 - 0.74 ; upper vs lower quartile ) for all-cause mortality . For cardiovascular mortality , the hazard ratio was 0.23 ( 95 % confidence interval , 0.10 - 0.55 ) when adjusted for age , sex , chronic disease , education , smoking , alcohol consumption , history of cardiovascular disease or hypertension , body mass index , and total cholesterol level . Protective trend relationships were observed between the level of optimism and all-cause and cardiovascular mortality ( P<.001 and P = .001 for trend , respectively ) . Interaction with sex ( P = .04 ) supported a stronger protective effect of optimism in men than women for all-cause mortality but not for cardiovascular mortality . CONCLUSIONS Our results provide support for a grade d and independent protective relationship between dispositional optimism and all-cause mortality in old age . Prevention of cardiovascular mortality accounted for much of the effect A proportion of patients do not recover fully from surgery or they develop chronic postsurgical pain . The aim of this study was to examine the incidence and predictors of unfavourable long‐term outcome after surgery using a prospect i ve cohort design Objectives : In 2009 , Gramke and colleagues have described predictive factors to preoperatively detect those at risk for moderate to severe acute postsurgical pain ( APSP ) after day surgery . The aim of the present study is to externally vali date this initial model and to improve and internally vali date a modified version of this model . Material s and Methods : Elective patients scheduled for day surgery were prospect ively enrolled from November 2008 to April 2010 . Model discrimination was quantified using the area under the receiver operating characteristic curve ( AUC ) . Model calibration was assessed by visual inspection of the calibration plot . Subsequently , we modified ( different assignment of type of surgery , different cutoff for moderate to severe APSP , continuous of dichotomized variables and testing of additional variables ) and internally vali date d this model by st and ard bootstrapping techniques . Results : A total of 1118 patients were included . The AUC for the original model was 0.81 in the derivation data set and 0.72 in our validation data set . The model showed poorly calibrated risk predictions . The AUC of the modified model was 0.82 ( optimism-corrected AUC=0.78 ) . This modified model showed good calibration . Conclusions : The original prediction model of Gramke and colleagues performed insufficiently on our cohort of out patients with respect to discrimination and calibration . Internal validation of a modified model shows promising results . In this model , preoperative pain , patient derived expected pain , and different types of surgery are the strongest predictors of moderate to severe APSP after day surgery Objective : To identify somatic and psychologic predictors of pain , functional limitations , global perceived recovery , and quality of life 6 months after surgical intervention . Summary Background Data : Recent studies have indicated that chronic pain after surgical intervention is more common than previously assumed . Several demographic and somatic predictors of long-term unfavorable outcome have been identified , but little is known about the contribution of psychologic risk factors . Methods : A prospect i ve cohort study , including 625 patients undergoing elective surgery at the University Hospital Maastricht , The Netherl and s , was conducted between February and August 2003 . Psychologic question naires were completed preoperatively and acute postoperative pain was recorded until 4 days after the operation . Six months later , all patients received follow-up question naires to assess pain , functional limitations , global perceived recovery , and quality of life . Multivariable logistic regression analyses were used to estimate relative risk of poor outcome in terms of pain , functional limitations , and global recovery . Multivariable linear regression analysis was used to assess associations with quality of life at 6 months . Results : The most important somatic predictors of unfavorable outcome were duration of the operation and high levels of acute postoperative pain . Patients reporting high levels of pain 4 days after the operation and patients undergoing an operation of longer than 3 hours were at risk for increased pain , increased functional limitations , poor global recovery , and reported lower levels of quality of life 6 months after the operation . Psychologic variables that influenced long-term outcome were preoperative fear of surgery and optimism . Fear of the long-term consequences of the operation was associated with more pain , poor global recovery , and worse quality of life 6 months later , whereas optimism was associated with better recovery and higher quality of life . Conclusions : This study was the first to identify the joint contribution of somatic and psychologic factors to chronic pain , functional limitations , and quality of life 6 months after surgical interventions . It replicates previous findings that intense acute postoperative pain is a risk factor for long-term adverse outcome and also identified additional risk factors , namely , long duration of the operation , ASA status , and preoperative fear of surgery Objectives : To prospect ively describe the prevalence and predictive factors of chronic postsurgical pain ( CPSP ) and poor global recovery in a large outpatient population at a university hospital , 1 year after outpatient surgery . Material s and Methods : A prospect i ve longitudinal cohort study was performed . During 18 months , patients presenting for preoperative assessment were invited to participate . Outcome parameters were measured by using question naires at 3 timepoints : 1 week preoperatively , 4 days postoperatively , and 1 year postoperatively . A value of > 3 on an 11-point numeric rating scale was considered to indicate moderate to severe pain . A score of ⩽80 % on the Global Surgical Recovery Index was defined as poor global recovery . Results : A total of 908 patients were included . The prevalence of moderate to severe preoperative pain was 37.7 % , acute postsurgical pain 26.7 % , and CPSP 15.3 % . Risk factors for the development of CPSP were surgical specialty , preoperative pain , preoperative analgesic use , acute postoperative pain , surgical fear , lack of optimism , and poor preoperative quality of life . The prevalence of poor global recovery was 22.3 % . Risk factors for poor global recovery were recurrent surgery because of the same pathology , preoperative pain , preoperative analgesic use , surgical fear , lack of optimism , poor preoperative and acute postoperative quality of life , and follow-up surgery during the first postoperative year . Discussion : Moderate to severe CPSP after outpatient surgery is common , and should not be underestimated . Patients at risk for developing CPSP can be identified during the preoperative phase The aim of this study was to investigate the role of dispositional optimism ( DO ) as a predictor of health-related quality of life ( HRQL ) in a sample of upper aerodigestive tract cancer ( UADT ) patients . A prospect i ve observational study design was used with a cohort of patients from one centre . DO was evaluated using a French version of the Life Orientation Test ( the FLOT ) translated and vali date d for this study . HRQL was evaluated using the EORTC QLQ-C30 prior to and 3 months following treatment . The association between FLOT ratings and HRQL was evaluated using linear multiple regression analysis and a two-way ANOVA with repeated measures . Baseline data were gathered on 101 subjects and follow-up data on 88 of these . The sample was dichotomized around the median FLOT score creating ‘ optimist ’ and ‘ pessimist ’ groups . Before treatment , optimists reported better role , cognitive and emotional function , less pain and fatigue and a better global rating of HRQL than did pessimists . Following treatment , optimists reported better role and cognitive functioning , less pain and better global HRQL than did pessimists . Pessimists reported a greater deterioration in the role domain following treatment than did optimists . At no point did pessimists rate HRQL better than optimists . The results suggest that optimism is associated with better HRQL in French UADT cancer patients UNLABELLED The clinical pattern of neuropathic pain , diagnosed using the quantitative sensory testing ( QST ) battery ( German Research Network on Neuropathic Pain ) , could be partly mimicked in healthy volunteers after topical capsaicin application . However , similar to clinical neuropathic pain that develops in only a subgroup of patients who have a neurologic lesion , this attempt to mimick a neuropathic pain pattern succeeded only in a small fraction ( 18 % ) of healthy individuals . In the present assessment , we pursued the hypothesis that the inducible subgroup differed from the other healthy participants with respect to their psychological phenotype . Therefore , in an observational study , participants were assessed using a comprehensive set of psychological variables comprising general psychological and pain-related cognitive-emotional mechanisms . The sum scores of the question naires were significantly linearly correlated with each other . Principal component analysis indicated that a major source of variance ( 46 % ) could be attributed to dispositional optimism examined via the Life Orientation Test ( LOT ) . The LOT score significantly differed between the groups of participants , either those in whom a neuropathy-like pattern of pain assessed via QST could be partly ( 50 - 60 % of the 11 QST parameters ) induced ( n = 20 ) or not ( n = 90 ; P = .0375 ) . It emerged again as the main selection criterion in a classification and regression tree predicting a participant 's group assignment ( inducible neuropathy-like QST pattern versus noninducible neuropathy-like QST pattern ) at a cross-vali date d accuracy of 95.5 ± 2.1 % . Thus , the few participants in a r and om sample of healthy volunteers who , after topical capsaicin application , partly resemble ( to a degree of about 60 % ) the clinical pattern of neuropathic pain in the QST test battery , are preselectable on the basis of psychological factors , with a particular emphasis on pessimistic life attitudes . PERSPECTIVE In a small fraction of 18 % of healthy volunteers , topical capsaicin application result ed in a neuropathy-like pattern in 50 to 60 % of the components of a clinical test battery . These individuals displayed a more pessimistic life attitude as assessed by means of the LOT Summary Risk factors for chronic pain up to 9 months after breast cancer surgery include younger age , psychological vulnerability , axillary clearance surgery , and severe acute postoperative pain . ABSTRACT Chronic postsurgical pain ( CPSP ) is a common postoperative adverse event affecting up to half of women undergoing breast cancer surgery , yet few epidemiological studies have prospect ively investigated the role of preoperative , intraoperative , and postoperative risk factors for pain onset and chronicity . We prospect ively investigated preoperative sociodemographic and psychological factors , intraoperative clinical factors , and acute postoperative pain in a prospect i ve cohort of 362 women undergoing surgery for primary breast cancer . Intraoperative nerve h and ling ( division or preservation ) of the intercostobrachial nerve was recorded . At 4 and 9 months after surgery , incidence of chronic painful symptoms not present preoperatively was 68 % and 63 % , respectively . Univariate analysis revealed that multiple psychological factors and nerve division was associated with chronic pain at 4 and 9 months . In a multivariate model , independent predictors of CPSP at 4 months included younger age and acute postoperative pain ( odds ratio [ OR ] 1.34 , 95 % confidence interval [ CI ] 1.12 to 1.60 ) , whereas preoperative psychological robustness ( OR 0.70 , 95 % CI 0.49 to 0.99 ) , a composite variable comprising high dispositional optimism , high positive affect , and low emotional distress , was protective . At 9 months , younger age , axillary node clearance ( OR 2.97 , 95 % CI 1.09 to 8.06 ) , and severity of acute postoperative pain ( OR 1.17 , 95 % CI 1.00 to 1.37 ) were predictive of pain persistence . Of those with CPSP , 25 % experienced moderate to severe pain and 40 % were positive on Douleur Neuropathique 4 and Self‐Complete Leeds Assessment of Neuropathic Symptoms and Signs pain scales . Overall , a high proportion of women report painful symptoms , altered sensations , and numbness in the upper body within the first 9 months after resectional breast surgery and cancer treatment In the present study , we investigated longitudinally ( baseline , 10 weeks , 16 weeks ) whether patient personality traits , such as dispositional optimism and mastery , play a role in patients ' ability to effectively control the severity of their pain and fatigue in the context of a symptom control intervention among patients with cancer . Two hundred fourteen patients currently undergoing chemotherapy received a baseline interview followed by a 10-week , nurse-assisted symptom control intervention . At 10 weeks , patients received a second interview to assess the effectiveness of the intervention , with a final follow-up interview at 16 weeks . R and om effects regression models were used to investigate the effects of mastery and optimism on the severity of pain and fatigue , adjusting for the effects of other important covariates , such as age , gender , cancer site , stage of disease , and comorbidity . Patients who were older , more optimistic , suffered from fewer comorbid conditions , or reported higher levels of mastery tended to report less severe pain , whereas higher levels of mastery and fewer comorbid conditions predicted lower fatigue severity scores . These findings underscore the need for physicians and nurses involved in the care of cancer patients to recognize , encourage , promote , and take advantage of these traits in their patients to help them more effectively manage their cancer care , so that they ultimately can achieve a better quality of life during the sequelae of the cancer experience BACKGROUND After surgery , patient reports or health care professional evaluations of heightened acute pain intensity should lead to extra analgesia provision , which is design ated by rescue analgesia ( RA ) . Whether RA is administered or not , it is not directly dependent on the patient but rather on clinical decisions , which should be based on pain management guidelines . There is a general lack of studies focusing on pain-related decision-making regarding RA provision . OBJECTIVES This study aim ed to examine which pre and post-surgical factors , beyond acute post-surgical pain intensity , might influence clinical decisions on RA administration after major joint arthroplasties ( MJA ) . METHODS A consecutive sample of 110 patients undergoing MJA was fully assessed 24 hours before ( T1 ) and 48 hours after ( T2 ) surgery . Before surgery , baseline demographic , clinical , and psychological variables were evaluated and after surgery the main outcome was RA provision , with acute post-surgical pain intensity being also registered . STUDY DESIGN Prospect i ve observational cohort study . SETTING Central hospital in northern Portugal . RESULTS Logistic regression analysis revealed that RA provision , after MJA , is influenced by a patient-related psychological factor , pain catastrophizing ( OR = 1.143 ; 95 % CI 1.044 - 1.253 , P = 0.004 ) , above and beyond acute post-surgical pain intensity . Additionally , the type of arthroplasty ( OR = 2.806 ; 95 % CI 1.002 - 7.857 , P = 0.050 ) also affected RA provision . Other patient-related factors such as gender , previous pain states , pre-surgical optimism , and post-surgical anxiety did not reveal any predictive role in RA administration . LIMITATIONS This is a single-site study , only confined to MJA patients . CONCLUSIONS The findings of this study shed light on the importance of psychological factors in determining RA provision following MJA . This encourages further reflection on acute post-surgical pain management by health care providers , namely by raising clinicians ' awareness about the factors that influence patient-provider interactions , as well as their impact on decision-making regarding RA provision . A global assessment of patients , wherein psychological variables are taken into account , is warranted in order to improve the quality of surgical pain management . Finally , these findings provide support for the design of acute post-surgical pain management interventions directed at clinicians , in order to augment professionals ' awareness about the potential influence of patient-related psychological factors on RA decisions Objective : The present study sought to determine whether job insecurity is associated with personality traits and beliefs . In addition , it was tested whether aspects of personality confounded the relationships between job insecurity and health , or moderated this association . Methods : At the first data collection , 5163 persons participated , and at the second data collection , 1946 persons of a r and om sample participated . Data were obtained from Oslo Health Study . Results : The job insecurity aspect concerning confidence in having a good job in 2 years was more strongly related to the health variables , and particularly with mental distress , compared with other aspects of job insecurity . Type-A behavior predicted an increase in upper back pain ( & bgr ; 0.07 ) , while optimism predicted a change in lower back pain ( & bgr ; −0.07 ) . Conclusions : Job insecurity is associated with health ; this association is strongest for mental distress and self-reported health , and weaker for back-pain A significant proportion of patients experience chronic post-surgical pain ( CPSP ) following inguinal hernia surgery . Psychological models are useful in predicting acute pain after surgery , and in predicting the transition from acute to chronic pain in non-surgical context s. This is a prospect i ve cohort study to investigate psychological ( cognitive and emotional ) risk factors for CPSP after inguinal hernia surgery . Participants were asked to complete question naires before surgery and 1 week and 4 months after surgery . Data collected before surgery and 1 week after surgery were used to predict pain at 4 months . Psychological risk factors assessed included anxiety , depression , fear-avoidance , activity avoidance , catastrophizing , worry about the operation , activity expectations , perceived pain control and optimism . The study included 135 participants ; follow-up question naires were returned by 119 ( 88.1 % ) and 115 ( 85.2 % ) participants at 1 week and 4 months after surgery respectively . The incidence of CPSP ( pain at 4 months ) was 39.5 % . After controlling for age , body mass index and surgical variables ( e.g. anaesthetic , type of surgery and mesh type used ) , lower pre-operative optimism was an independent risk factor for CPSP at 4 months ; lower pre-operative optimism and lower perceived control over pain at 1 week after surgery predicted higher pain intensity at 4 months . No emotional variables were independently predictive of CPSP . Further research should target these cognitive variables in pre-operative psychological preparation for surgery The connections of certain clinico-physiological indicators of health state , chronic diseases , felt symptoms , and psychic well-being with self-rated health were studied among men of different ages as a part of the more extensive research project Jyväskylä Studies on Functional Aging . Study population was selected by using systematic r and om sampling among men aged 31 to 35 , 51 to 55 and 71 to 75 years in the city of Jyväskylä . Log-linear and logit models as well as regression and structural equation models within the framework of LISREL were used as methods of analysis . The associations between general self-rated health and the explanative variables were different in different age groups : In the youngest age group self-rated health was best explained by symptoms and index of physical fitness ; among the middle-aged by symptoms and psychic well-being ; and among the oldest by chronic diseases . The results suggest that self-rated health belongs to the important indicators of health , and more attention should be paid to it both in research and in medical practice UNLABELLED Based on prior research identifying dispositional optimism as a predictor of placebo responding , the present study tested the hypothesis that individuals high in optimism would be more likely to respond to a placebo analgesic . Optimists and pessimists were r and omly assigned to a placebo expectation condition or a no expectation condition before a cold pressor task . Blood pressure and heart rate were recorded before and during the cold pressor task , and participant ratings of pain and expectations were obtained immediately after the task . Analysis of the expectation manipulation revealed that the placebo instruction was successful in altering participant expectancy during the cold pressor . Supporting the main hypothesis , dispositional optimism was associated with lower pain ratings in the placebo condition but not in the control condition . Because dispositional optimism can alter placebo responding to laboratory pain , future studies should examine the potential role that this individual difference factor may play in patient responsivity to pharmacological and nonpharmacological treatments for clinical pain . PERSPECTIVE This study examined the possibility that individual differences can predict placebo analgesia . Participants were r and omly assigned to receive either a placebo expectation or no expectation before a cold pressor task . Dispositional optimism was related to less cold pressor pain in the placebo condition as compared with the control condition BACKGROUND We investigate to what extent pain in older individuals is predicted by on the one h and chronic morbidity as a resistance deficit , and on the other h and psychological resistance re sources and the sense of coherence . For the first time , we tested the salutogenic hypothesis that the sense of coherence mediates the relationship between re sources /deficits and pain . METHODS In our question naire study , we assessed selected psychological resistance re sources ( self-esteem , generalized self-efficacy , optimism , and social support ) , the number of self-reported medical diagnoses of chronic illness , the sense of coherence , and pain ( SF-36 Bodily Pain subscale ) in a sample of 387 older persons ( at the mean age of 73.8 years ) . RESULTS Using hierarchical regression , we found that morbidity and sense of coherence were the only significant predictors of pain , with morbidity showing the strongest effect . Using path analysis , the sense of coherence was a mediator of the relationship between resistance re sources /deficits and pain . CONCLUSIONS With respect to our analytical model , in which pain experience was the criterion variable , morbidity and the sense of coherence are important predictors of pain . Moreover , we found evidence for the salutogenic idea that the sense of coherence represents a mediator variable as it pools resistance/deficits influences on pain . We recommend a prospect i ve design to explore these assumed causal chains in future research Abstract Background and purpose Dealing with chronic pain is difficult and affects physiological as well as psychological well-being . Patients with chronic pain are often reporting concurrent emotional problems such as low mood and depressive symptoms . Considering this , treatments need to involve strategies for improving mood and promoting well-being in this group of patients . With the rise of the positive psychology movement , relatively simple intervention strategies to increase positive feelings , cognitions , and behaviours have become available . So far , the evidence for positive psychology techniques mainly comes from studies with healthy participants , and from studies with patients expressing emotional problems such as depression or anxiety as their main complaint . This study describes an initial attempt to explore the potential effects of a positive psychology intervention in a small sample of patients suffering from chronic pain . Methods A replicated single case design was employed with five participants . The participants started to fill out daily self-reports and weekly question naires two weeks before the intervention started , and continued throughout the intervention . In addition , they filled out a battery of question naires at pretest , posttest , and at a three months follow-up . The instruments for assessment were selected to cover areas and constructs which are important for pain problems in general ( e.g. disability , life satisfaction , central psychological factors ) as well as more specific constructs from positive psychology ( e.g. compassion , savoring beliefs ) . Results The results on pre and post assessment s showed an effect on some of the measures . However , according to a more objective measure of reliable change ( Reliable Change Index , RCI ) , the effects were quite modest . On the weekly measures , there was a trend towards improvements for three of the participants , whereas the other two basically did not show any improvement . The daily ratings were rather difficult to interpret because of their large variability , both between and within individuals . For the group of participants as a whole , the largest improvements were on measures of disability and catastrophizing . Conclusions The results of this preliminary study indicate that a positive psychology intervention may have beneficial effects for some chronic pain patients . Although it is not to be expected that a limited positive psychology intervention on its own is sufficient to treat pain-related disability in chronic patients , our findings suggest that for some it may be an advantageous complement to enhance the effects of other interventions . Implication s The results of this pilot study about the potential effects of a positive psychology intervention for chronic pain patients may be encouraging , warranting a larger r and omized controlled study . Future studies may also concentrate on integrating positive psychology techniques into existing treatments , such as composite CBT-programs for chronic pain patients . Our advice is that positive psychology interventions are not to be regarded as st and -alone treatments for this group of patients , but may potentially enhance the effect of other interventions . However , when and for which patients these techniques may be recommended is to be explored in future research |
12,442 | 30,763,436 | Conclusions and Relevance The findings from this study suggest that a range of efficient therapies with different safety profiles is available for patients with NETs | Importance Multiple therapies are currently available for patients with neuroendocrine tumors ( NETs ) , yet many therapies have not been compared head-to-head within r and omized clinical trials ( RCTs ) .
Objective To assess the relative safety and efficacy of therapies for NETs . | BACKGROUND In the phase 3 RADIANT-4 trial , everolimus increased progression-free survival compared with placebo in patients with advanced , progressive , non-functional , well-differentiated gastrointestinal or lung neuroendocrine tumours ( NETs ) . We now report the health-related quality of life ( HRQOL ) secondary endpoint . METHODS RADIANT-4 is a multicentre , r and omised , double-blind , placebo-controlled , phase 3 trial done in 97 centres in 25 countries worldwide . Adults ( aged ≥18 years ) were eligible for the study if they had pathologically confirmed , advanced ( unresectable or metastatic ) , non-functional , well-differentiated ( grade 1 or 2 ) NETs of lung or gastrointestinal origin . Patients were r and omly allocated ( 2:1 ) using block r and omisation ( block size of three ) by an interactive voice response system to receive oral everolimus ( 10 mg per day ) or placebo , both with best supportive care , with stratification by tumour origin , WHO performance status , and previous somatostatin analogue treatment . HRQOL was assessed with the Functional Assessment of Cancer Therapy-General ( FACT-G ) question naire at baseline ( visit 2 , day 1 ) , every 8 weeks ( ± 1 week ) during the study for the first 12 months after r and omisation , and every 12 weeks thereafter until study drug discontinuation . The primary endpoint , reported previously , was progression-free survival assessed by central review ; HRQOL was a prespecified secondary endpoint . The prespecified secondary outcome measure was time to definitive deterioration ( ≥7 points ) in FACT-G total score . Analyses were done on the full analysis set , consisting of all r and omised patients , by intention to treat . Only data obtained while receiving the r and omly allocated treatment were included in this analysis . Enrolment for RADIANT-4 was completed on Aug 23 , 2013 , but the trial is ongoing pending final analysis of the key secondary endpoint of overall survival . This trial is registered with Clinical Trials.gov , number NCT01524783 . FINDINGS Between April 3 , 2012 , and Aug 23 , 2013 , 302 patients were enrolled ; 205 were r and omly allocated everolimus and 97 were assigned placebo . At baseline , 193 ( 94 % ) of 205 patients assigned everolimus and 95 ( 98 % ) of 97 allocated placebo had completed either fully or partly the FACT-G question naire ; at week 48 , 70 ( 83 % ) of 84 patients assigned everolimus and 22 ( 85 % ) of 26 allocated placebo completed FACT-G. Median time to definitive deterioration in FACT-G total score was 11·27 months ( 95 % CI 9·27 - 19·35 ) with everolimus and 9·23 months ( 5·52-not estimable ) with placebo ( adjusted hazard ratio 0·81 , 95 % CI 0·55 - 1·21 ; log-rank p=0·31 ) . INTERPRETATION HRQOL was maintained for patients with advanced , non-functional , gastrointestinal or lung NETs , with no relevant differences noted between the everolimus and placebo groups . In view of the previous RADIANT-4 findings of longer progression-free survival with everolimus , our findings suggest that everolimus delays disease progression while preserving overall HRQOL , even with the usual toxic effects related to active targeted drug treatment for cancer . FUNDING Novartis Pharmaceuticals Purpose Treatment options for neuroendocrine tumors ( NETs ) remain limited . This trial assessed the progression-free survival ( PFS ) of bevacizumab or interferon alfa-2b ( IFN-α-2b ) added to octreotide among patients with advanced NETs . Patients and Methods Southwest Oncology Group ( SWOG ) S0518 , a phase III study conducted in a US cooperative group system , enrolled patients with advanced grade s 1 and 2 NETs with progressive disease or other poor prognostic features . Patients were r and omly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week . The primary end point was central ly assessed PFS . This trial is registered with Clinical Trials.gov as NCT00569127 . Results A total of 427 patients was enrolled , of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b . The median PFS by central review was 16.6 months ( 95 % CI , 12.9 to 19.6 months ) in the bevacizumab arm and was 15.4 months ( 95 % CI , 9.6 to 18.6 months ) in the IFN arm ( hazard ratio [ HR ] , 0.93 ; 95 % CI , 0.73 to 1.18 ; P = .55 ) . By site review , the median PFS times were 15.4 months ( 95 % CI , 12.6 to 17.2 months ) for bevacizumab and 10.6 months ( 95 % CI , 8.5 to 14.4 months ) for interferon ( HR , 0.90 ; 95 % CI , 0.72 to 1.12 ; P = .33 ) . Time to treatment failure was longer with bevacizumab than with IFN ( HR , 0.72 ; 95 % CI , 0.58 to 0.89 ; P = .003 ) . Confirmed radiologic response rates were 12 % ( 95 % CI , 8 % to 18 % ) for bevacizumab and 4 % ( 95 % CI , 2 % to 8 % ) for IFN . Common adverse events with bevacizumab and octreotide included hypertension ( 32 % ) , proteinuria ( 9 % ) , and fatigue ( 7 % ) ; with IFN and octreotide , they included fatigue ( 27 % ) , neutropenia ( 12 % ) , and nausea ( 6 % ) . Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms , which suggests that these agents have similar antitumor activity among patients with advanced NETs PURPOSE Effective systemic therapy for advanced carcinoid is lacking . The combination of bevacizumab ( BEV ) and pegylated ( PEG ) interferon alpha-2b was evaluated among patients with metastatic or unresectable carcinoid tumors . PATIENTS AND METHODS Forty-four patients on stable doses of octreotide were r and omly assigned to 18 weeks of treatment with bevacizumab or PEG interferon alpha-2b . At disease progression ( PD ) or at the end of 18 weeks ( whichever occurred earlier ) , patients received bevacizumab plus PEG interferon until progression . Functional computer tomography ( CT ) scans were performed to measure effect on tumor blood flow . RESULTS In the bevacizumab arm , four patients ( 18 % ) achieved confirmed partial response ( PR ) , 17 patients ( 77 % ) had stable disease ( SD ) , and one patient ( 5 % ) had PD . In the PEG interferon arm , 15 patients ( 68 % ) had SD and six patients ( 27 % ) had PD . Progression-free survival ( PFS ) rates after 18 weeks of monotherapy were 95 % in bevacizumab versus 68 % on the PEG interferon arm . The overall median PFS for all 44 patients is 63 weeks . Compared with paired baseline measurements on functional CT scans , we observed a 49 % ( P < .01 ) and 28 % ( P < .01 ) decrease in tumor blood flow at day 2 and week 18 among patients treated with bevacizumab . No significant changes in tumor blood flow were observed following PEG interferon . PEG interferon alpha-2b treatment was associated with decrease in plasma basic fibroblast growth factor ( bFGF ; P = .04 ) and increase in plasma interleukin-18 ( IL-18 ; P < .01 ) . No significant changes in bFGF or IL-18 following treatment with bevacizumab were observed . CONCLUSION Bevacizumab therapy result ed in objective responses , reduction of tumor blood flow , and longer PFS in patients with carcinoid than PEG interferon treatment These guidelines up date previous guidance published in 2005 . They have been revised by a group who are members of the UK and Irel and Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology , the Society for Endocrinology , the Association of Surgeons of Great Britain and Irel and ( and its Surgical Specialty Associations ) , the British Society of Gastrointestinal and Abdominal Radiology and others . The authors hip represents leaders of the various groups in the UK and Irel and Neuroendocrine Tumour Society , but a large amount of work has been carried out by other specialists , many of whom attended a guidelines conference in May 2009 . We have attempted to represent this work in the acknowledgements section . Over the past few years , there have been advances in the management of neuroendocrine tumours , which have included clearer characterisation , more specific and therapeutically relevant diagnosis , and improved treatments . However , there remain few r and omised trials in the field and the disease is uncommon , hence all evidence must be considered weak in comparison with other more common cancers . BACKGROUND The combination of streptozocin and fluorouracil has become the st and ard therapy for advanced islet-cell carcinoma . However , doxorubicin has also been shown to be active against this type of tumor , as has chlorozotocin , a drug that is structurally similar to streptozocin but less frequently causes vomiting . METHODS In this multicenter trial , we r and omly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens : streptozocin plus fluorouracil , streptozocin plus doxorubicin , or chlorozotocin alone . The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens . RESULTS Streptozocin plus doxorubicin was superior to streptozocin plus fluorouracil in terms of the rate of tumor regression , measured objective ly ( 69 percent vs. 45 percent , P = 0.05 ) , and the length of time to tumor progression ( median , 20 vs. 6.9 months ; P = 0.001 ) . Streptozocin plus doxorubicin also had a significant advantage in terms of survival ( median , 2.2 vs. 1.4 years ; P = 0.004 ) that was accentuated when we considered long-term survival ( greater than 2 years ) . Chlorozotocin alone produced a 30 percent regression rate , with the length of time to tumor progression and the survival time equivalent to those observed with streptozocin plus fluorouracil . Crossover therapy after the failure of either chlorozotocin alone or one of the combination regimens produced an overall response rate of only 17 percent , and the responses were transient . Toxic reactions to all regimens included vomiting , which was least severe with chlorozotocin ; hematologic depression ; and , with long-term therapy , renal insufficiency . CONCLUSIONS The combination of streptozocin and doxorubicin is superior to the current st and ard regimen of streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma . Chlorozotocin alone is similar in efficacy to streptozocin plus fluorouracil , but it produces fewer gastrointestinal side effects than the regimens containing streptozocin . It therefore merits study as a constituent of combination drug regimens BACKGROUND Effective systemic therapies for patients with advanced , progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce . We aim ed to assess the efficacy and safety of everolimus compared with placebo in this patient population . METHODS In the r and omised , double-blind , placebo-controlled , phase 3 RADIANT-4 trial , adult patients ( aged ≥18 years ) with advanced , progressive , well-differentiated , non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide . Eligible patients were r and omly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo , both with supportive care . Patients were stratified by tumour origin , performance status , and previous somatostatin analogue treatment . Patients , investigators , and the study sponsor were masked to treatment assignment . The primary endpoint was progression-free survival assessed by central radiology review , analysed by intention to treat . Overall survival was a key secondary endpoint . This trial is registered with Clinical Trials.gov , number NCT01524783 . FINDINGS Between April 3 , 2012 , and Aug 23 , 2013 , a total of 302 patients were enrolled , of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo . Median progression-free survival was 11·0 months ( 95 % CI 9·2 - 13·3 ) in the everolimus group and 3·9 months ( 3·6 - 7·4 ) in the placebo group . Everolimus was associated with a 52 % reduction in the estimated risk of progression or death ( hazard ratio [ HR ] 0·48 [ 95 % CI 0·35 - 0·67 ] , p<0·00001 ) . Although not statistically significant , the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death ( HR 0·64 [ 95 % CI 0·40 - 1·05 ] , one-sided p=0·037 , whereas the boundary for statistical significance was 0·0002 ) . Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis ( in 18 [ 9 % ] of 202 patients in the everolimus group vs 0 of 98 in the placebo group ) , diarrhoea ( 15 [ 7 % ] vs 2 [ 2 % ] ) , infections ( 14 [ 7 % ] vs 0 ) , anaemia ( 8 [ 4 % ] vs 1 [ 1 % ] ) , fatigue ( 7 [ 3 % ] vs 1 [ 1 % ] ) , and hyperglycaemia ( 7 [ 3 % ] vs 0 ) . INTERPRETATION Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours . The safety findings were consistent with the known side-effect profile of everolimus . Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours , including those arising from the pancreas , lung , and gastrointestinal tract . FUNDING Novartis Pharmaceuticals Corporation OBJECTIVES To compare the effect of octreotide with f placebo on symptoms , tumour marker and quality of life in patients with gastrointestinal neuroendocrine tumours and liver metastases . DESIGN A blinded , placebo-controlled , cross-over study was performed . The number of flushing epidodes and diarrhoea episodes were registered for 1 week prior to the study and for the 8-week duration of the study . Quality of life and 24-h urinary 5-hydroxyindoleacetic acid ( 5-HIAA ) excretion were measured before the start , and at 4 and 8 weeks . Quality of life was registered with the Psychosocial Adjustment to Illness Scale ( PAIS ) and 5-HIAA measured by high-performance chromatography with electrochemical detection . 5-HIAA values exceeding 45 mumol 24 h-1 were considered to be elevated . SETTING The study was performed in a tertiary referral centre . SUBJECTS Twelve patients were approached ; eleven patients were included , with a mean age of 56.5 ( range 30 - 72 ) years . The primary tumour originated from the small intestine in nine and from the pancreas in two patients . The main symptoms were diarrhoea , flushing and nausea . The 24-h excretion of 5-HIAA was increased in all patients . INTERVENTIONS Patients were treated for 4 weeks with octreotide ( 100 micrograms ) subcutaneously , twice daily , and for 4 weeks on placebo ( octreotide vehicle ) in r and om starting order . MAIN OUTCOME MEASURES The main outcome measures were the number of episodes of the main clinical symptom(s ) and 24-h 5-HIAA excretion . RESULTS Octreotide lowered diarrhoea and flushing frequency significantly compared to placebo . 5-HIAA excretion was reduced during treatment with the active drug . Two domains of the PAIS were significantly improved , indicating that the reduction of tumour marker and symptoms were clinical ly important . CONCLUSIONS The clinical effect of octreotide on symptoms in patients with neuroendocrine tumours was demonstrated in a controlled , prospect i ve trial Purpose Preliminary studies suggested that telotristat ethyl , a tryptophan hydroxylase inhibitor , reduces bowel movement ( BM ) frequency in patients with carcinoid syndrome . This placebo-controlled phase III study evaluated telotristat ethyl in this setting . Patients and Methods Patients ( N = 135 ) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy received ( 1:1:1 ) placebo , telotristat ethyl 250 mg , or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period . The primary end point was change from baseline in BM frequency . In an open-label extension , 115 patients subsequently received telotristat ethyl 500 mg . Results Estimated differences in BM frequency per day versus placebo averaged over 12 weeks were -0.81 for telotristat ethyl 250 mg ( P < .001 ) and ‒0.69 for telotristat ethyl 500 mg ( P < .001 ) . At week 12 , mean BM frequency reductions per day for placebo , telotristat ethyl 250 mg , and telotristat ethyl 500 mg were -0.9 , -1.7 , and -2.1 , respectively . Responses , predefined as a BM frequency reduction ≥ 30 % from baseline for ≥ 50 % of the double-blind treatment period , were observed in 20 % , 44 % , and 42 % of patients given placebo , telotristat ethyl 250 mg , and telotristat ethyl 500 mg , respectively . Both telotristat ethyl dosages significantly reduced mean urinary 5-hydroxyindole acetic acid versus placebo at week 12 ( P < .001 ) . Mild nausea and asymptomatic increases in gamma-glutamyl transferase were observed in some patients receiving telotristat ethyl . Follow-up of patients during the open-label extension revealed no new safety signals and suggested sustained BM responses to treatment . Conclusion Among patients with carcinoid syndrome not adequately controlled by somatostatin analogs , treatment with telotristat ethyl was generally safe and well tolerated and result ed in significant reductions in BM frequency and urinary 5-hydroxyindole acetic acid BACKGROUND The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in pre clinical models and phase 1 and 2 trials . METHODS We conducted a multinational , r and omized , double-blind , placebo-controlled phase 3 trial of sunitinib in patients with advanced , well-differentiated pancreatic neuroendocrine tumors . All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline . A total of 171 patients were r and omly assigned ( in a 1:1 ratio ) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo . The primary end point was progression-free survival ; secondary end points included the objective response rate , overall survival , and safety . RESULTS The study was discontinued early , after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib . Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group ( hazard ratio for progression or death , 0.42 ; 95 % confidence interval [ CI ] , 0.26 to 0.66 ; P<0.001 ) . A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied . The objective response rate was 9.3 % in the sunitinib group versus 0 % in the placebo group . At the data cutoff point , 9 deaths were reported in the sunitinib group ( 10 % ) versus 21 deaths in the placebo group ( 25 % ) ( hazard ratio for death , 0.41 ; 95 % CI , 0.19 to 0.89 ; P=0.02 ) . The most frequent adverse events in the sunitinib group were diarrhea , nausea , vomiting , asthenia , and fatigue . CONCLUSIONS Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival , overall survival , and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00428597 . ) Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors ( NET ) compared with placebo in the RADIANT-3 study . Here , we present the final overall survival ( OS ) data and data on the impact of biomarkers on OS from the RADIANT-3 study . Methods Patients with advanced , progressive , low- or intermediate- grade pancreatic NET were r and omly assigned to everolimus 10 mg/day ( n = 207 ) or placebo ( n = 203 ) . Crossover from placebo to open-label everolimus was allowed on disease progression . Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator 's discretion ( extension phase ) . OS analysis was performed using a stratified log-rank test in the intent-to-treat population . The baseline levels of chromogranin A , neuron-specific enolase , and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored . Results Of 410 patients who were enrolled between July 2007 and March 2014 , 225 received open-label everolimus , including 172 patients ( 85 % ) r and omly assigned initially to the placebo arm . Median OS was 44.0 months ( 95 % CI , 35.6 to 51.8 months ) for those r and omly assigned to everolimus and 37.7 months ( 95 % CI , 29.1 to 45.8 months ) for those r and omly assigned to placebo ( hazard ratio , 0.94 ; 95 % CI , 0.73 to 1.20 ; P = .30 ) . Elevated baseline chromogranin A , neuron-specific enolase , placental growth factor , and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS . The most common adverse events included stomatitis , rash , and diarrhea . Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced , progressive pancreatic NET , the longest OS reported in a phase III study for this population . Everolimus was associated with a survival benefit of 6.3 months , although this finding was not statistically significant . Crossover of patients likely confounded the OS results BACKGROUND Everolimus , an oral inhibitor of the mammalian target of rapamycin ( mTOR ) , has shown antitumour activity in patients with advanced pancreatic neuroendocrine tumours . We aim ed to assess the combination of everolimus plus octreotide long-acting repeatable ( LAR ) in patients with low- grade or intermediate- grade neuroendocrine tumours ( carcinoid ) . METHODS We did a r and omised , double-blind , placebo-controlled , phase 3 study comparing 10 mg per day oral everolimus with placebo , both in conjunction with 30 mg intramuscular octreotide LAR every 28 days . R and omisation was by interactive voice response systems . Participants were aged 18 years or older , with low- grade or intermediate- grade advanced ( unresectable locally advanced or distant metastatic ) neuroendocrine tumours , and disease progression established by radiological assessment within the past 12 months . Our primary endpoint was progression-free survival . Adjusted for two interim analyses , the prespecified boundary at final analysis was p≤0·0246 . This study is registered at Clinical Trials.gov , number NCT00412061 . FINDINGS 429 individuals were r and omly assigned to study groups ; 357 participants discontinued study treatment and one was lost to follow-up . Median progression-free survival by central review was 16·4 ( 95 % CI 13·7 - 21·2 ) months in the everolimus plus octreotide LAR group and 11·3 ( 8·4 - 14·6 ) months in the placebo plus octreotide LAR group ( hazard ratio 0·77 , 95 % CI 0·59 - 1·00 ; one-sided log-rank test p=0·026 ) . Drug-related adverse events ( everolimus plus octreotide LAR vs placebo plus octreotide LAR ) were mostly grade 1 or 2 , and adverse events of all grade s included stomatitis ( 62%vs 14 % ) , rash ( 37%vs 12 % ) , fatigue ( 31%vs 23 % ) , and diarrhoea ( 27%vs 16 % ) . INTERPRETATION Everolimus plus octreotide LAR , compared with placebo plus octreotide LAR , improved progression-free survival in patients with advanced neuroendocrine tumours associated with carcinoid syndrome . FUNDING Novartis Pharmaceuticals Objective The objective of this analysis was to compare patient-reported outcomes and health-related quality of life ( HRQoL ) in a pivotal phase III trial of sunitinib versus placebo in patients with progressive , well-differentiated pancreatic neuroendocrine tumors ( NCT00428597 ) . Patients and Methods Patients received sunitinib 37.5 mg ( n = 86 ) or placebo ( n = 85 ) on a continuous daily-dosing schedule until disease progression , unacceptable adverse events ( AEs ) , or death . Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Question naire – Core 30 at baseline , Day 1 of every 4-week cycle , and end of treatment or withdrawal . Changes ≥10 points on each scale or item were deemed clinical ly meaningful . Results Sunitinib had anti-tumor effects and improved progression-free survival ( PFS ) compared with placebo . The study was terminated early for this reason and because of more serious AEs and deaths with placebo . Baseline HRQoL scores were well balanced between study arms , and were generally maintained over time in both groups . In the first 10 cycles , there were no significant differences between groups in global HRQoL , cognitive , emotional , physical , role , and social functioning domains , or symptom scales , except for worsening diarrhea with sunitinib ( p < 0.0001 vs. placebo ) . Insomnia also worsened with sunitinib ( p = 0.0372 vs. placebo ) , but the difference was not clinical ly meaningful . Conclusion With the exception of diarrhea ( a recognized side effect ) , sunitinib had no impact on global HRQoL , functional domains , or symptom scales during the progression-free period . Hence , in patients with pancreatic neuroendocrine tumors , sunitinib provided a benefit in PFS without adversely affecting OBJECTIVE To evaluate the efficacy and safety of lanreotide depot/autogel 120 mg for the control of carcinoid syndrome ( CS ) symptoms in patients with neuroendocrine tumors ( NETs ) . METHODS This was a 16-week , r and omized , double-blind , phase 3 trial ( Clinical trials.gov : NCT00774930 ) . Patients with/without prior somatostatin analog ( SSA ) use were r and omized to lanreotide depot/autogel 120 mg or placebo every 4 weeks , with access to short-acting octreotide as rescue medication . The primary endpoint was the percentage of days in which short-acting octreotide was used , which was assessed from daily diaries using an analysis of covariance including the stratification variables baseline short-acting octreotide use and frequency of diarrhea/flushing . The proportions of patients experiencing treatment success was a supportive analysis . Adverse events were recorded at all visits . RESULTS A total of 115 patients were enrolled ( lanreotide , n = 59 ; placebo , n = 56 ) . The adjusted mean ( 95 % confidence interval [ CI ] ) percentage of days with rescue octreotide use ( primary endpoint ) was significantly lower in the lanreotide ( 33.7 % ; 95 % CI , 25.0%-42.4 % ) versus the placebo group ( 48.5 % ; 95 % CI , 39.6%-57.4 % ) , representing an absolute difference of -14.8 % ( 95 % CI , -26.8 % to -2.8 % ; P = .017 ) . The odds ratio of full/partial treatment success ( ≤3 days short-acting octreotide use weeks 12 to 15 ) was significantly greater with lanreotide than placebo ( 2.4 ; 95 % CI , 1.1 - 5.3 ; P = .036 ) . No new safety concerns were identified , and lanreotide was well tolerated . CONCLUSION Lanreotide depot/autogel is effective for the control of CS symptoms in patients ( SSA-naïve or experienced ) with NETs . ABBREVIATIONS AE = adverse event BMI = body mass index CS = carcinoid syndrome ELECT = Evaluating Lanreotide Efficacy and safety as a Carcinoid-syndrome Treatment HRQoL = health-related quality of life LTOLE = long-term open-label extension NET = neuroendocrine tumor OL = open label SSA = somatostatin analog BACKGROUND & AIMS The effect of octreotide plus interferon-alpha versus octreotide monotherapy on the primary study end points of time to treatment failure ( progression , death , stop of study treatment ) and long-term survival was investigated in patients with progressive metastatic neuroendocrine foregut ( mainly pancreatic ) and midgut tumors . METHODS One hundred nine of 125 registered patients were r and omized starting in January 1995 , and 105 patients ( 51 monotherapy , 54 combination treatment ) were finally analyzed in March 2000 . Tumor growth was assessed at 3-month intervals by computed tomography or magnetic resonance imaging . Long-term survival was studied up to April 2004 in all analyzed patients and in 9 patients not r and omized because of stable disease . RESULTS Partial tumor regression occurred in 2.9 % , 1.9 % , and 5.7 % and stabilization of tumor growth in 44.8 % , 27.6 % , and 15.2 % at 3 , 6 , and 12 months , respectively , with no significant differences between both treatment arms . In March 2000 , 9.5 % of patients were in treatment . Time to treatment failure and long-term survival did not differ significantly between the 2 groups , with a median survival of 32 and 54 months for the octreotide and the combination groups , respectively . Survival was longer in patients not r and omized because of stable disease ( median , 68 months ) and in those with low nuclear Ki-67 . A trend toward longer survival was shown for patients with slow spontaneous tumor growth before r and omization . Patients responding to treatment lived longer than unresponsive patients . CONCLUSIONS Combination treatment was not superior to monotherapy concerning progression-free and long-term survival . Patients responding to treatment and those with slow spontaneous tumor growth had a survival advantage BACKGROUND Cytotoxic chemotherapy is widely used for advanced , unresectable pancreatic and other gastrointestinal foregut neuroendocrine tumours ( NETs ) and the most commonly used regimen combines 5-fluorouracil with streptozocin . The NET01 trial was design ed to investigate whether capecitabine combined with streptozocin was an acceptable regimen with or without adding cisplatin . METHODS Patients with advanced , unresectable NETs of pancreatic , gastrointestinal foregut or unknown primary site were r and omised to receive three-weekly capecitabine ( Cap ) 625 mg/m(2 ) twice daily orally , streptozocin ( Strep ) 1.0 g/m(2 ) intravenously on day 1 , with or without cisplatin ( Cis ) 70 mg/m(2 ) intravenously on day 1 . The primary outcome measure was objective response . Secondary outcome measures included progression-free and overall survival , quality of life , toxicity and biochemical response . RESULTS 86 ( 44 CapStrep , 42 CapStrepCis ) patients were r and omised . Best objective response rate was 12 % ( 95 % confidence interval (CI)=2 - 22 % ) with CapStrep and 16 % ( 95 % CI=4 - 27.4 % ) with CapStrepCis . Disease-control rate was 80 % with CapStrep and 74 % with CapStrepCis . The estimated median progression-free and overall survival were 10.2 and 26.7 months for CapStrep and 9.7 and 27.5 months for CapStrepCis . 44 % of CapStrep and 68 % of CapStrepCis patients experienced grade ≥3 adverse events . INTERPRETATION The efficacies of the novel CapStrep±Cis regimens were very similar . CapStrep was better tolerated than CapStrepCis . The trial was registered as EudraCT : 2004 - 005202 - 71 and IS RCT N : 35124268 194 Background : Currently , there are limited therapeutic options for patients with advanced midgut neuroendocrine tumors progressing on first-line somatostatin analog therapy . Methods : NETTER-1 is the first Phase III multicentric , r and omized , controlled trial evaluating 177Lu-DOTA0-Tyr3-Octreotate ( Lutathera ) in patients with inoperable , progressive , somatostatin receptor positive midgut NETs . 230 patients with Grade 1 - 2 metastatic midgut NETs were r and omized to receive Lutathera 7.4 GBq every 8 weeks ( x4 administrations ) versus Octreotide LAR 60 mg every 4-weeks . The primary endpoint was PFS per RECIST 1.1 criteria , with objective tumor assessment performed by an independent reading center every 12 weeks . Secondary objectives included objective response rate , overall survival , toxicity , and health-related quality of life . Results : Enrolment was completed in February 2015 , with a target of 230 patients r and omized ( 1:1 ) in 36 European and 15 sites in the United States . At the time of statistical analysis , In a r and omized controlled study , 20 patients with malignant carcinoid tumors were included . Ten patients received streptozocin plus 5-fluorouracil for 6 months and another 10 human leukocyte interferon ( IFN ) . After 6 months of treatment , an objective tumor response was noted in five of the patients treated with IFN ( 50 % ) but in none of the patients on chemotherapy . Stable disease was found in five patients ( 50 % ) on IFN treatment and four ( 40 % ) on chemotherapy . Progressive disease was noted in six of the patients ( 60 % ) receiving chemotherapy . A statistical analysis using the chi-square test showed a significantly higher proportion of responders and stable disease in the IFN treated group ( P = 0.0039 ) . Furthermore , three of eight patients who had previously received chemotherapy showed later on an objective response to IFN . The objective responses were mainly noted in decreased tumor markers ; however , two patients also showed a significant reduction of tumor size . Subjective responses were noted in 72 % of patients treated with interferon , but only in 9 % of those treated with streptozocin plus 5-fluorouracil . The results indicate that interferon treatment is superior to the combination of streptozocin plus 5-fluorouracil . Considering both the therapeutic effects and adverse reactions , human leukocyte interferon is a promising alternative for treatment of patients with malignant carcinoid tumors The somatostatin analogues lanreotide and octreotide have previously been shown to be effective in controlling flushing and diarrhea in patients with carcinoid syndrome . As lanreotide requires injection only every 10 days , compared with twice‐daily injections of octreotide , a direct comparison between these two treatments in terms of patient acceptability , patient preference , and efficacy in controlling symptoms was performed in patients with carcinoid syndrome Midgut carcinoid tumours often present with widespread disease making curative surgery impossible . Medical treatment therefore plays a major role in the treatment of these patients Abstract Lessons Learned . Treatment with BEZ235 has not been shown to demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile . The hypothesis of dual targeting of the phosphatidylinositol 3‐kinase and mammalian target of rapamycin pathways in patients with advanced pancreatic neuroendocrine tumors may warrant further study using other agents . Background . This phase II study investigated whether targeting the phosphatidylinositol 3‐kinase (PI3K)/mammalian target of rapamycin ( mTOR ) pathway via PI3 K , mTOR complex 1 ( mTORC1 ) and mTOR complex 2 ( mTORC2 ) inhibition using BEZ235 may be more effective than mTORC1 inhibition with everolimus in patients with advanced pancreatic neuroendocrine tumors ( pNET ) who are naïve to mTOR inhibitor therapy . Methods . Patients with advanced pNET were r and omized ( 1:1 ) to oral BEZ235 400 mg twice daily or oral everolimus 10 mg once daily on a continuous dosing schedule . The primary endpoint was progression‐free survival ( PFS ) . Secondary endpoints included safety , overall response rate ( ORR ) , overall survival ( OS ) , and time to treatment failure . Results . Enrollment in this study was terminated early ( 62 enrolled of the 140 planned ) . The median PFS was 8.2 months ( 95 % confidence interval [ CI ] : 5.3 to not evaluable [ NE ] ) with BEZ235 versus 10.8 months ( 95 % CI : 8.1–NE ) with everolimus ( hazard ratio 1.53 ; 95 % CI : 0.72–3.25 ) . The most commonly reported all‐ grade adverse events ( > 50 % of patients regardless of study treatment relationship ) with BEZ235 were diarrhea ( 90.3 % ) , stomatitis ( 74.2 % ) , and nausea ( 54.8 % ) . Conclusion . BEZ235 treatment in mTOR inhibitor‐naïve patients with advanced pNET did not demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile The carcinoid syndrome , a common feature of small intestinal carcinoid tumors with liver metastases , includes flushing , diarrhea , bronchoconstriction , and right heart failure . The etiology of the carcinoid syndrome is not well understood , but serotonin seems to be involved in the diarrhea , whereas tachykinins may play a role in the flush reaction . In a double blind placebo-controlled study , we studied the effect of octreotide in 20 patients with midgut carcinoid tumors and liver metastases . A sc injection of 50 micrograms octreotide caused a significant ( P less than 0.001 ) decrease in median plasma tachykinins and serum pancreatic polypeptide , GH , and insulin for up to 4 h. Administration of octreotide ( 50 micrograms , twice daily , sc ) caused a 26 % decrease in urinary 5-hydroxyindoleacetia acid excretion , but the number of flushing attacks or bowel movements did not change significantly . A typical flush was provoked by pentagastrin , and plasma tachykinin and serotonin levels were measured . The flush reaction was grade d on a 10-point visual analog scale . Octreotide ( 50 micrograms , sc ) given 45 min before flush stimulation prevented tachykinin release completely and significantly reduced the median flushing score from 8.5 to 2 . Placebo administered in the same way did not prevent tachykinin release after pentagastrin administration . Thus , octreotide prevents pentagastrin-induced flushing and the related hormonal changes in patients with the carcinoid syndrome Background —Carcinoid diarrhoea is associated with rapid small bowel and proximal colonic transit . Intravenous administration of a serotonin type 3 receptor ( 5HT3 ) antagonist restores postpr and ial colonic tone towards normal in carcinoid patients . Aims —To evaluate the medium term effects of an oral 5HT3 antagonist , alosetron , on symptoms , stool fat , and transit in patients with carcinoid diarrhoea . Methods —In 27 patients with carcinoid diarrhoea , symptoms were recorded daily and gastrointestinal transit was measured by scintigraphy in a three dose ( 0.1 , 0.5 , 2.0 mg , twice daily ) , r and omised ( 1:1:1 ) , parallel group , four week study . Placebo was given during the first week . Loperamide ( 2 mg capsules ) was used as rescue medication . Results —There were numerical improvements in median diarrhoea score , stool weight , loperamide use , and overall colonic transit at four hours , but no overall significant drug effect was shown . Alosetron reduced the proximal colon emptying rate ( p<0.05 in 20 evaluable comparisons ) , but did not significantly alter small bowel transit . Conclusions —Alosetron retardation of proximal colonic emptying in patients with carcinoid diarrhoea confirms the potential role of a 5HT3 mechanism in this disorder . Doses of alosetron higher than 2.0 mg twice daily will be required for symptomatic benefit in carcinoid diarrhoea AIM Rectal carcinoid tumors smaller than 10 mm can be resected with local excision using endoscopy . In order to remove rectal carcinoid tumors completely , we evaluated endoscopic mucosal resection with a ligation device in this pilot control r and omized study . METHODS Fifteen patients were diagnosed with rectal carcinoid tumor ( less than 10 mm ) in our hospital from 1993 to 2002 . There were 9 males and 6 females , with a mean age 61.5 years ( range , 34 - 77 years ) . The patients had no complaints of carcinoid syndrome symptoms . Fifteen patients were r and omly divided into 2 groups : 7 carcinoid tumors were treated by conventional endoscopic resection , and 8 carcinoid tumors were treated by endoscopic resection using a ligation device . RESULTS All rectal carcinoid tumors were located at the middle to distal rectum . The size of the tumors varied from 3 mm to 10 mm and background characteristics of the patients were not different in the two groups . The rate of complete removal of carcinoid tumors using a ligation device ( 100 % , 8/8 ) was significantly higher than that of conventional endoscopic resection ( 57.1 % , 4/7 ) . The three patients had tumor involvement of deep margin , for which additional treatment was performed . No complications occurred during or after endoscopic resection using a ligation device . All patients in the both groups were alive during the 3-year observation period . CONCLUSION Endoscopic resection using a ligation device is a useful and safe method for resection of small rectal carcinoid tumors Accumulation of medical knowledge related to diagnosis and management over the last 5 - 6 decades has altered the course of diseases , improved clinical outcomes and increased survival . Thus , it has become difficult for the practicing physician to evaluate the long-term effects of a particular therapy on survival of an individual patient . Further , the approach by each physician to an individual patient with the same disease is not always uniform . In an attempt to assist physicians in applying newly acquired knowledge to patients , clinical practice guidelines were introduced by various scientific societies . Guidelines assist in facilitating the translation of new research discoveries into clinical practice ; however , despite the improvements over the years , there are still several issues related to guidelines that often appear ‘ lost in translation ' . Guidelines are based on the results of r and omized clinical trials , other nonr and omized studies , and expert opinion ( i.e. the opinion of most members of the guideline committees ) . The merits and limitations of r and omized clinical trials , guideline committees , and presentation of guidelines will be discussed . In addition , proposals to improve guidelines will be presented Background In a phase III trial in patients with advanced , well-differentiated , progressive pancreatic neuroendocrine tumors , sunitinib 37.5 mg/day improved investigator-assessed progression-free survival ( PFS ) versus placebo ( 11.4 versus 5.5 months ; HR , 0.42 ; P < 0.001 ) . Here , we present PFS using retrospective blinded independent central review ( BICR ) and final median overall survival ( OS ) , including an assessment highlighting the impact of patient crossover from placebo to sunitinib . Patients and methods In this r and omized , double-blind , placebo-controlled study , cross-sectional imaging from patients was evaluated retrospectively by blinded third-party radiologists using a two-reader , two-time-point lock , followed by a sequential locked-read , batch-mode paradigm . OS was summarized using the Kaplan-Meier method and Cox proportional hazards model . Crossover-adjusted OS effect was derived using rank-preserving structural failure time ( RPSFT ) analyses . Results Of 171 r and omized patients ( sunitinib , n = 86 ; placebo , n = 85 ) , 160 ( 94 % ) had complete scan sets/time points . By BICR , median ( 95 % confidence interval [ CI ] ) PFS was 12.6 ( 11.1 - 20.6 ) months for sunitinib and 5.8 ( 3.8 - 7.2 ) months for placebo ( HR , 0.32 ; 95 % CI 0.18 - 0.55 ; P = 0.000015 ) . Five years after study closure , median ( 95 % CI ) OS was 38.6 ( 25.6 - 56.4 ) months for sunitinib and 29.1 ( 16.4 - 36.8 ) months for placebo ( HR , 0.73 ; 95 % CI 0.50 - 1.06 ; P = 0.094 ) , with 69 % of placebo patients having crossed over to sunitinib . RPSFT analysis confirmed an OS benefit for sunitinib . Conclusions BICR confirmed the doubling of PFS with sunitinib compared with placebo . Although the observed median OS improved by nearly 10 months , the effect estimate did not reach statistical significance , potentially due to crossover from placebo to sunitinib . Trial registration number NCT00428597 Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first‐line somatostatin analogue therapy have limited therapeutic options . This r and omized , controlled trial evaluated the efficacy and safety of lutetium‐177 (177Lu)–Dotatate in patients with advanced , progressive , somatostatin‐receptor – positive midgut neuroendocrine tumors . Methods We r and omly assigned 229 patients who had well‐differentiated , metastatic midgut neuroendocrine tumors to receive either 177Lu‐Dotatate ( 116 patients ) at a dose of 7.4 GBq every 8 weeks ( four intravenous infusions , plus best supportive care including octreotide long‐acting repeatable [ LAR ] administered intramuscularly at a dose of 30 mg ) ( 177Lu‐Dotatate group ) or octreotide LAR alone ( 113 patients ) administered intramuscularly at a dose of 60 mg every 4 weeks ( control group ) . The primary end point was progression‐free survival . Secondary end points included the objective response rate , overall survival , safety , and the side‐effect profile . The final analysis of overall survival will be conducted in the future as specified in the protocol ; a prespecified interim analysis of overall survival was conducted and is reported here . Results At the data ‐cutoff date for the primary analysis , the estimated rate of progression‐free survival at month 20 was 65.2 % ( 95 % confidence interval [ CI ] , 50.0 to 76.8 ) in the 177Lu‐Dotatate group and 10.8 % ( 95 % CI , 3.5 to 23.0 ) in the control group . The response rate was 18 % in the 177Lu‐Dotatate group versus 3 % in the control group ( P<0.001 ) . In the planned interim analysis of overall survival , 14 deaths occurred in the 177Lu‐Dotatate group and 26 in the control group ( P=0.004 ) . Grade 3 or 4 neutropenia , thrombocytopenia , and lymphopenia occurred in 1 % , 2 % , and 9 % , respectively , of patients in the 177Lu‐Dotatate group as compared with no patients in the control group , with no evidence of renal toxic effects during the observed time frame . Conclusions Treatment with 177Lu‐Dotatate result ed in markedly longer progression‐free survival and a significantly higher response rate than high‐dose octreotide LAR among patients with advanced midgut neuroendocrine tumors . Preliminary evidence of an overall survival benefit was seen in an interim analysis ; confirmation will be required in the planned final analysis . Clinical ly significant myelosuppression occurred in less than 10 % of patients in the 177Lu‐Dotatate group . ( Funded by Advanced Accelerator Applications ; NETTER‐1 Clinical Trials.gov number , NCT01578239 ; EudraCT number 2011‐005049‐11 . |
12,443 | 22,071,811 | Sodium reduction result ed in a 1 % decrease in blood pressure in normotensives , a 3.5 % decrease in hypertensives , a significant increase in plasma renin , plasma aldosterone , plasma adrenaline and plasma noradrenaline , a 2.5 % increase in cholesterol , and a 7 % increase in triglyceride .
In general , these effects were stable in studies lasting for 2 weeks or more | BACKGROUND In spite of more than 100 years of investigations the question of reduced sodium intake as a health prophylaxis initiative is still unsolved .
OBJECTIVES To estimate the effects of low sodium versus high sodium intake on systolic and diastolic blood pressure ( SBP and DBP ) , plasma or serum levels of renin , aldosterone , catecholamines , cholesterol , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) and triglycerides . | A reduction in salt intake lowers blood pressure . However , most previous trials were in whites with few in blacks and Asians . Salt reduction may also reduce other cardiovascular risk factors ( eg , urinary albumin excretion , arterial stiffness ) . However , few well-controlled trials have studied these effects . We carried out a r and omized double-blind crossover trial of salt restriction with slow sodium or placebo , each for 6 weeks , in 71 whites , 69 blacks , and 29 Asians with untreated mildly raised blood pressure . From slow sodium to placebo , urinary sodium was reduced from 165±58 ( ±SD ) to 110±49 mmol/24 hours ( 9.7 to 6.5 g/d salt ) . With this reduction in salt intake , there was a significant decrease in blood pressure from 146±13/91±8 to 141±12/88±9 mm Hg ( P<0.001 ) , urinary albumin from 10.2 ( IQR : 6.8 to 18.9 ) to 9.1 ( 6.6 to 14.0 ) mg/24 hours ( P<0.001 ) , albumin/creatinine ratio from 0.81 ( 0.47 to 1.43 ) to 0.66 ( 0.44 to 1.22 ) mg/mmol ( P<0.001 ) , and carotid-femoral pulse wave velocity from 11.5±2.3 to 11.1±1.9 m/s ( P<0.01 ) . Subgroup analysis showed that the reductions in blood pressure and urinary albumin/creatinine ratio were significant in all groups , and the decrease in pulse wave velocity was significant in blacks only . These results demonstrate that a modest reduction in salt intake , approximately the amount of the current public health recommendations , causes significant falls in blood pressure in all 3 ethnic groups . Furthermore , it reduces urinary albumin and improves large artery compliance . Although both could be attributable to the falls in blood pressure , they may carry additional benefits on reducing cardiovascular disease above that obtained from the blood pressure falls alone Objective — To study the possible pathophysiological implication s of long continued dietary sodium restriction in pregnancy Objective : To determine the blood pressure responses in elderly normotensive men and women to dietary sodium and to the diunsaturated fatty acid dihomogammalinolenic acid ( DGLA ) , which is derived from linoleic acid Design : Blood pressure responses were assessed in 66 subjects ( 36 male , 30 female ; mean age 65 years ) on two diets differing by approximately 70mmol/day sodium , combined with daily supplements of either 1 g DGLA or 1 g safflower oil , giving a four-group parallel design . After a common period of salt restriction and salt supplementation , two sets of parallel groups continued with either salt or placebo tablets . The study was blinded , except for dietary adjustments based on 24-h urinary sodium excretion values measured once every 2 weeks . Blood pressures were also measured automatically once every 2 weeks Results : Urinary sodium excretion ( sodium intake ) correlated significantly with systolic and diastolic blood pressures . A strong interaction with sex ( P < 0.001 for systolic blood pressure ) reflected greater responsiveness in women to changing sodium intake . A second major determinant of blood pressure responsiveness was the waist : hip ratio , an index of central obesity ; this correlation was independent of the initial sodium intake , initial blood pressure or body mass index . The waist : hip ratio was a powerful predictor of blood pressure changes with sodium intake in women only ; women with and roid fat distribution were , similarly to men , less sensitive to dietary sodium . Daily supplements of 1 g DGLA doubled the concentration of DGLA in plasma but did not influence blood pressure Conclusions : Among elderly normotensive subjects , women responded to changes in sodium intake with greater changes in blood pressure than men did . Furthermore , this response was strongly related to the gynaecoid distribution of body The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake . Sixty-three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a " low sodium " diet ( less than 60 mmol/day ) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets . Subjects were then r and omly assigned to either drink a low alcohol beer alone for a 4-week period ( reducing their self-reported alcohol consumption from 537 to 57 ml/week ) or to continue their usual alcohol intake ( 543 versus 557 ml/week ) . Within the low and normal alcohol intake groups , subjects were assigned to either a low or normal sodium intake . The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks . This result ed in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day . The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets , and their urinary sodium excretion remained unchanged ( 125 versus 142 mmol/day ) . Regular antihypertensive therapy was continued throughout . Fifty-nine subjects completed the trial . In those who reduced their alcohol intake there was a fall in both systolic blood pressure ( -5.4 mm Hg supine , p less than 0.01 ) and diastolic blood pressure ( -3.2 mm Hg supine , p less than 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS This study was design ed to evaluate in healthy volunteers the renal hemodynamic and tubular effects of the orally active angiotensin II receptor antagonist losartan ( DuP 753 or MK 954 ) . Losartan or a placebo was administered to 23 subjects maintained on a high-sodium ( 200 mmol/d ) or a low-sodium ( 50 mmol/d ) diet in a r and omized , double-blind , crossover study . The two 6-day diet periods were separated by a 5-day washout period . On day 6 , the subjects were water loaded , and blood pressure , renal hemodynamics , and urinary electrolyte excretion were measured for 6 hours after a single 100-mg oral dose of losartan ( n = 16 ) or placebo ( n = 7 ) . Losartan induced no significant changes in blood pressure , glomerular filtration rate , or renal blood flow in these water-loaded subjects , whatever the sodium diet . In subjects on a low-salt diet , losartan markedly increased urinary sodium excretion from 115 + /- 9 to 207 + /- 21 mumol/min ( P < .05 ) . The fractional excretion of endogenous lithium was unchanged , suggesting no effect of losartan on the early proximal tubule in our experimental conditions . Losartan also increased urine flow rate ( from 10.5 + /- 0.4 to 13.1 + /- 0.6 mL/min , P < .05 ) ; urinary potassium excretion ( from 117 + /- 6.9 to 155 + /- 11 mumol/min ) ; and the excretion of chloride , magnesium , calcium , and phosphate . In subjects on a high-salt diet , similar effects of losartan were observed , but the changes induced by the angiotensin II antagonist did not reach statistical significance . In addition , losartan demonstrated significant uricosuric properties with both sodium diets . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of the present study was to evaluate the effects of a normal-sodium ( 120 mmol sodium ) diet compared with a low-sodium diet ( 80 mmol sodium ) on readmissions for CHF ( congestive heart failure ) during 180 days of follow-up in compensated patients with CHF . A total of 232 compensated CHF patients ( 88 female and 144 male ; New York Heart Association class II-IV ; 55 - 83 years of age , ejection fraction < 35 % and serum creatinine < 2 mg/dl ) were r and omized into two groups : group 1 contained 118 patients ( 45 females and 73 males ) receiving a normal-sodium diet plus oral furosemide [ 250 - 500 mg , b.i.d . ( twice a day ) ] ; and group 2 contained 114 patients ( 43 females and 71 males ) receiving a low-sodium diet plus oral furosemide ( 250 - 500 mg , b.i.d . ) . The treatment was given at 30 days after discharge and for 180 days , in association with a fluid intake of 1000 ml per day . Signs of CHF , body weight , blood pressure , heart rate , laboratory parameters , ECG , echocardiogram , levels of BNP ( brain natriuretic peptide ) and aldosterone levels , and PRA ( plasma renin activity ) were examined at baseline ( 30 days after discharge ) and after 180 days . The normal-sodium group had a significant reduction ( P<0.05 ) in readmissions . BNP values were lower in the normal-sodium group compared with the low sodium group ( 685+/-255 compared with 425+/-125 pg/ml respectively ; P<0.0001 ) . Significant ( P<0.0001 ) increases in aldosterone and PRA were observed in the low-sodium group during follow-up , whereas the normal-sodium group had a small significant reduction ( P=0.039 ) in aldosterone levels and no significant difference in PRA . After 180 days of follow-up , aldosterone levels and PRA were significantly ( P<0.0001 ) higher in the low-sodium group . The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels , and PRA . The results of the present study show that a normal-sodium diet improves outcome , and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients . Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet Objective : To examine effects of dietary fish oil supplementation with sodium restriction on blood pressure in the elderly . Design : In a double-blind dietary intervention lasting 4 weeks , parallel comparisons of blood pressure were made in volunteers assigned to one of four treatment groups : fish oil and low sodium ; fish oil and normal sodium ; sunflower oil and low sodium ; or sunflower oil and normal sodium . Setting : Subjects lived at home and attended our nutrition research clinic at fortnightly intervals for dietary counselling and blood pressure measurement . Participants : Health volunteers aged 60 - 80 years were sought by advertisement . A total of 114 men and women were enrolled in two cohorts ; 106 , with an initial mean blood pressure of 132/77 mmHg , satisfactorily completed the study . Intervention : All subjects adopted a low-sodium diet and dietary changes were effected by double-blind administration of slow-release sodium chloride or placebo tablets , along with capsules containing either fish or sunflower oil . Main outcome measure : The primary measure was the within-subject change in blood pressure after 4 weeks of intervention in each dietary treatment group . Results : Urinary sodium excretion in subjects on low-sodium diets decreased whilst potassium excretion was unaffected . Systolic blood pressure ( SBP ) fell in the group taking sunflower oil with low sodium , but there was only a transient fall in diastolic blood pressure ( DBP ) . In those taking fish oil with normal sodium , the change in blood pressure was not significant , except after adjustment for initial blood pressure and weight changes . When fish oil was combined with low sodium , however , both SBP and DBP were substantially reduced ; the reduction in DBP was significantly greater than in the other treatment groups . Conclusion : Dietary fish oil and sodium restriction can interact to lower DBP in the elderly If high sodium intake is involved in the pathogenesis of essential hypertension , the effects of changing the sodium intake should be demonstrable in the susceptible part of the normotensive population . Therefore , we have investigated the effects of moderate salt restriction in 52 young normotensive subjects with and without a family history of hypertension ; 22 ( 42 % ) responded to moderate salt restriction ( 200 to 50 mmol/day ) over 2 weeks , with a significant fall in blood pressure shown by continuous automatic blood pressure recordings . Accordingly , these subjects were classified as salt-sensitive , and the remainder as salt-resistant . Compared to salt-resistant subjects , salt-sensitive subjects showed a 2.5-fold higher incidence of a positive family history of hypertension ( p less than 0.01 ) , and a significantly higher blood pressure and lower salivary sodium concentration during the usual high sodium diet . Although there were no differences in Na , K-ATPase activity and in Na-K cotransport of erythrocytes , the pressor response to infused norepinephrine in salt-sensitive subjects was double that of salt-resistant subjects independent of the diet and this was linked to indirect evidence for enhanced proximal tubular sodium reabsorption . On the usual high sodium diet , 40 % of the normal population may be salt-sensitive and prone to develop hypertension . Hypersensitivity to catecholamines ( genetically determined ? ) may be the cause of salt sensitivity . A low sodium concentration in saliva deserves further study as a simple screening test to identify salt-sensitive subjects High blood pressure and proteinuria are the major risk factors for cardiovascular and renal disease . In black individuals , there is an increased risk of hypertension , stroke , heart failure , and kidney disease . There are no controlled studies of the effects of reducing salt intake on blood pressure and urine protein excretion in black individuals . Therefore , the aim of our study was to determine the effects of modest salt restriction on blood pressure and urine protein excretion in nondiabetic black hypertensive subjects . The study was r and omized , double blind , and placebo controlled . After run-in periods on their usual diet and on reduced salt , participants continued to restrict their salt intake and then received either slow sodium tablets , design ed to bring their salt intake back to normal , or placebo tablets for 4 weeks in a r and omized , double-blind , crossover study . In the 40 who completed the study , urinary sodium excretion fell on slow sodium to placebo from 169±73 to 89±52 mmol per 24 hours ( P<0.001 ; ≈10 to 5 g salt per day ) . Blood pressure fell from 159/101±13/8 to 151/98±13/8 mm Hg ( P<0.01 ) . Protein excretion fell from 93±48 mg to 75±30 mg per 24 hours ( P<0.008 ) . Thus , reducing salt intake from ≈10 to 5 g per day reduced blood pressure and urine protein excretion in black hypertensives . In light of these findings , we would recommend that all black individuals with raised blood pressure reduce their salt intake to ≤5 g per day 1 . Seventeen normal volunteers aged 19 to 22 were r and omly subjected , in a trial of crossover design , to three distinct regimens of sodium chloride intake : high ( 16 to 20 g ) , normal ( 8 to 12 g ) and low ( 0.5 to 1 g ) . Each regimen lasted nine days , with determination of blood pressure and heart rate ( in the supine position and after sudden rising ) , body weight , and urinary output of creatinine , sodium and potassium on the third , sixth and ninth days . In addition , plasma levels of creatinine , sodium and potassium were determined on the ninth day so that sodium and potassium clearance and fractional excretion could be calculated . 2 . Eleven of the volunteers had a family history of hypertension . Compared to the six without such a history , these subjects showed : 1 ) higher supine systolic blood pressure on the third day of sodium overload ( 124.7 + /- 3.0 vs 112.3 + /- 2.9 mmHg , P less than 0.02 ) ; 2 ) higher supine diastolic blood pressure on the third day of sodium overload ( 76.5 + /- 2.8 vs 64.5 + /- 4.3 mmHg ; P less than 0.05 ) ; 3 ) higher supine diastolic blood pressure on the sixth day of sodium overload ( 73.7 + /- 2.3 vs 63.8 + /- 3.2 mmHg , P less than 0.05 ) ; 4 ) lower supine heart rate on the ninth day of sodium overload ( 61.0 + /- 3.1 vs 72.7 + /- 4.6 , P less than 0.05 ) , and 5 ) lower plasma potassium on the ninth day of sodium overload ( 4.10 + /- 0.05 vs 4.28 + /- 0.06 mEq/l , P less than 0.05 ) . 3 . These results suggest that normal individuals whose familial history places them at risk for the development of hypertension differ from those not at risk during their adaptation to sodium load by suffering a transient elevation of blood pressure within a few days of the increase in load . The low levels of plasma potassium observed in these volunteers after a period of sodium load may be due to the operation of different renal mechanisms of sodium excretion in this group , leading to increased kaliuresis , and may explain the high vascular reactivity of such individuals In 25 out patients with essential hypertension , sodium sensitivity , defined as the difference in mean arterial pressure ( delta MAP ) between 2 weeks of high-sodium ( 300 mmol per day ) and 2 weeks of low-sodium ( LS ) intake ( 50 - 100 mmol per day ) , was studied in relation to the plasma norepinephrine ( NE ) level , NE release , and pressor response to intravenous NE . In addition , forearm blood flow ( FBF ) was measured by plethysmography . There were two control periods of regular sodium intake , one of 4 weeks ' duration at the beginning of the study and one of 2 weeks ' duration at the end . The delta MAP ranged from + 18 to -8 mm Hg . The eight patients in whom delta MAP was greater than 10 mm Hg were regarded as salt-sensitive . When compared with salt-insensitive subjects , salt-sensitive patients had higher plasma NE levels in the control period ( p less than 0.05 ) and after 2 weeks of HS intake ( p less than 0.01 ) . Sodium sensitivity was directly related to the change in plasma NE between the HS and LS periods ( p less than 0.001 ) . The NE release decreased in salt-insensitive subjects whereas it increased in salt-sensitive patients between the LS and HS periods . Changes in NE release were directly related to sodium sensitivity ( p less than 0.05 ) . The pressor response to NE was not significantly influenced by changes in sodium intake . The FBF fell in salt-sensitive patients and increased in salt-insensitive subjects between the LS and HS periods . Sodium sensitivity was directly related to the change in forearm vascular resistance ( p less than 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Our recent studies have indicated that severe salt restriction aggravates vascular insulin resistance in younger normotensive and hypertensive subjects . However , whether the extent of dietary salt restriction commonly advocated adversely affects vascular insulin resistance is unknown . To determine whether moderate dietary salt restriction might affect vascular and systemic sensitivity to insulin , we studied eight subjects after 1 week of a normal sodium diet ( 235 mEq/day ) and 1 week of a moderate salt restriction ( 75 meq/day ) . Systemic insulin resistance as assessed by the fasting plasma glucose-to-insulin ratio was aggravated by dietary sodium restriction ( normal sodium : 1.2 + /- 0.1 mmol/mIU ; low sodium 0.6 + /- 0.1 , P < .05 ) . Salt restriction significantly reduced maximal insulin-mediated vasodilation ( normal sodium : 51 % + /- 5 % of maximum nitroglycerin-mediated response ; low sodium : 28 % + /- 6 % , P < .01 ) . In contrast , no alterations in nitroglycerin-mediated vasodilation nor phenylephrine-mediated vasoconstriction were noted . These studies demonstrate that moderate salt restriction aggravates both systemic and vascular insulin resistance . This impairment of the vasodilating effect of insulin could be a factor attenuating the blood pressure lowering effect of a low sodium diet BACKGROUND Few trials have evaluated the effects of reduced sodium intake in older individuals , and no trial has examined the effects in relevant subgroups such as African Americans . PATIENTS AND METHODS The effects of sodium reduction on blood pressure ( BP ) and hypertension control were evaluated in 681 patients with hypertension , aged 60 to 80 years , r and omly assigned to a reduced sodium intervention or control group . Participants ( 47 % women , 23 % African Americans ) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication . Three months after the start of intervention , medication was withdrawn . The primary end point was occurrence of an average systolic BP of 150 mm Hg or more , an average diastolic BP of 90 mm Hg or more , the resumption of medication , or a cardiovascular event during follow-up ( mean , 27.8 months ) . RESULTS Compared with control , mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group ( P<.001 ) ; significant reductions in sodium excretion occurred in subgroups defined by sex , race , age , and obesity . Prior to medication withdrawal , mean reductions in systolic and diastolic BPs from the reduced sodium intervention , net of control , were 4.3 mm Hg ( P<.001 ) and 2.0 mm Hg ( P = .001 ) . During follow-up , an end point occurred in 59 % of reduced sodium and 73 % of control group participants ( relative hazard ratio = 0.68 , P<.001 ) . In African Americans , the corresponding relative hazard ratio was 0.56 ( P = .005 ) ; results were similar in other subgroups . In dose-response analyses , end points were progressively less frequent with greater sodium reduction ( P for trend = .002 ) . CONCLUSION A reduced sodium intake is a broadly effective , nonpharmacologic therapy that can lower BP and control hypertension in older individuals SUMMARY To examine the Interactions between sodium balance and the sympathetic nervous system , we studied eight normotensive men after high ( 800 mEq/day ) and low ( 10 mEq/day ) sodium intake . We measured blood pressure ( BP ) , arterial , venous , and urinary norepinepfarine ( NE ) before and during incremental infusion of NE . We found significant direct , linear relationships ( p < 0.001 ) between the dose of NE infused and arterial and venous NE levels , and with mean arterial BP at both levels of sodium balance . In addition , the sensitivity was greater and the threshold of pressor response to NE as well as the basal concentrations of NE in arterial and venous plasma significantly lower ( p < 0.05 ) after the high sodium period . These observations expose heretofore unrecognized qualitative and quantitative interactions between sodium balance and NE that are capable of influencing BP in man Blood pressure responses to 1 week of low-salt ( 20 mmol sodium/d ) and high-salt ( 300 mmol sodium/d ) intake were investigated in a single-blind r and omized study in 163 white , nonobese normotensive subjects ( 65 women and 98 men ; mean age , 38 + /- 1.2 years ) . The individuals were classified as salt sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high-salt intake , as salt resistant when mean arterial blood pressure changed by less than 5 mm Hg , and as " counterregulator " when mean arterial blood pressure fell by at least 5 mm Hg during the high-salt diet . Reexamination of 31 subjects showed that this approach to the testing of salt sensitivity was reliable and reproducible . Thirty subjects ( 18.4 % ) were classified as salt sensitive , 108 ( 66.3 % ) as salt resistant , and 25 ( 15.3 % ) as counterregulators . Multiple regression analysis revealed that age , body weight , and family history of hypertension contributed significantly to the change in blood pressure after the diets . Salt sensitivity was more frequent in older subjects and in those with a positive family history of hypertension . An increase in blood pressure after salt restriction was more likely in younger individuals and in those with a negative family history of hypertension . Plasma renin activity and plasma aldosterone concentrations were lower in salt-sensitive compared with salt-resistant and counterregulating subjects . The rise in plasma renin activity during salt restriction was most pronounced in counterregulating subjects . Plasma norepinephrine concentrations were not different among the groups . ( ABSTRACT TRUNCATED AT 250 WORDS The blood pressure-raising effect of sodium chloride in salt-sensitive individuals depends on the administration of both sodium and chloride . While sodium chloride is well known to suppress the activity of the renin-angiotensin-aldosterone and the sympathetic nervous system , the effects of nonchloride sodium salts on the response of these systems to physiological stimuli have not been previously studied . We therefore examined the effect of dietary intake of sodium chloride or sodium citrate on the activity of the renin-angiotensin-aldosterone and the sympathetic nervous system during rest and following stimulation by active orthostasis in normotensive salt-sensitive ( n = 7 ) and salt-resistant ( n = 8) subjects . The subjects were given a low-salt diet ( 20 mmol/day ) for 3 weeks , to which a supplement of 200 mmol sodium per day , provided as either sodium chloride or sodium citrate , or a placebo , was added for 1 week each . We found that sodium chloride raised blood pressure in the salt-sensitive subjects ( P < .005 ) , while sodium citrate did not . Both salts , however , led to a similar suppression of the plasma levels of renin activity , angiotensin II , aldosterone , and norepinephrine ( P < .01 ) . Both sodium salts attenuated the renin response to orthostasis in salt-sensitive and salt-resistant individuals ( P < .01 ) , but the orthostasis-induced rise in renin activity was significantly smaller in the salt-sensitive than in the salt-resistant group under both sodium salts ( P < .05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS We studied the effect of high and low NaCl diets in normotensive and borderline hypertensive subjects to determine if a high NaCl diet produces abnormal renal vasoconstriction during the stress of upright posture in borderline hypertensive subjects . We studied 13 normotensive young men with diastolic blood pressures below 85 mm Hg and nine borderline hypertensive young men defined by diastolic blood pressures intermittently above 90 mm Hg . The subjects achieved comparable sodium balance during 6 days of low NaCl ( 10 mEq Na , 40 mEq Cl , 100 mEq K ) and high NaCl ( 400 mEq Na , 400 mEq Cl , 100 mEq K ) diets . In the normotensive subjects , st and ing for 30 minutes result ed in a tendency for diastolic blood pressure to fall during both diets . In contrast , during st and ing borderline hypertensive subjects showed no change in diastolic blood pressure during the low salt diet and a tendency for diastolic blood pressure to increase after the high salt diet . St and ing reduced renal plasma flow in both groups during both diets . However , only during the high NaCl diet did the absolute decrease and percent decrease in renal plasma flow during st and ing differ significantly ( p less than 0.05 and p less than 0.01 , respectively ) between the borderline hypertensive ( -151 + /- 24 ml/min/1.73m2 ; -29 + /- 4 % ) and normotensive subjects ( -79 + /- 17 ml/min/1.73m2 ; -15 + /- 3 % ) . The result ant increase in the renal vascular resistance index with st and ing did not differ between the two groups during the low NaCl diet . ( ABSTRACT TRUNCATED AT 250 WORDS The effects of long-term sodium restriction on plasma atrial natriuretic factor ( ANF ) concentrations , and the role of baseline plasma ANF concentration as an indicator of changes in haemodynamics and left ventricular hypertrophy during this treatment were studied in 40 middle-aged previously untreated mildly to moderately hypertensive men and women in a 6-month controlled r and omized study . The main emphasis of the treatment programme was to reduce daily sodium intake to less than 70 mmol . Mean sodium excretion decreased from 148 + /- 74 mmol 24 h-1 to 79 + /- 71 mmol 24 h-1 in the treatment group , but remained unchanged in the control group ( 173 + /- 68 mmol 24 h-1 vs. 186 + /- 62 mmol 24 h-1 ; P less than 0.01 for the difference in changes between the groups ) . Mean plasma ANF concentrations in the treatment group were 52.4 + /- 20.7 ( median 50 ) pg ml-1 at baseline and 38.7 + /- 26.3 ( median 42 ) pg ml-1 at 6 months , and the corresponding values in the control group were 55.5 + /- 20.5 ( median 50 ) pg ml-1 and 46.1 + /- 32.4 ( median 50 ) pg ml-1 , respectively ( P = NS for the difference in changes ) . The ANF concentration decreased from 70 + /- 14 pg ml-1 to 32 + /- 26 pg ml-1 in treated subjects with a high baseline plasma ANF concentration ( greater than 50 pg ml-1 ) , but increased from 37 + /- 11 pg ml-1 to 45 + /- 27 pg ml-1 in subjects with a low baseline plasma ANF concentration ( less than or equal to 50 pg ml-1 ) ( difference in changes P less than 0.001 ) . Compared with treated subjects with low baseline plasma ANF levels and with controls , treated subjects with high baseline plasma ANF levels showed a decrease ( P less than 0.05 ) in interventricular septal and left posterior wall thicknesses , in relative wall thickness , and in peripheral resistance . These results suggest that in mildly to moderately hypertensive subjects long-term sodium restriction decreases high plasma ANF concentrations concomitantly with regression of concentric left ventricular hypertrophy , probably as a result of changes in haemodynamics Abstract —An ouabain-like factor has been implicated repeatedly in salt-sensitive hypertension as a natriuretic agent . However , the response of plasma ouabain-like factor to acute and chronic variation of body sodium is unclear . We studied 138 patients with essential hypertension who underwent an acute volume expansion/contraction maneuver ( 2 days ) and 20 patients who entered a blind r and omized crossover design involving chronically controlled sodium intake and depletion ( 170 to 70 mmol/d ; 2 weeks each period ) . In both studies , plasma levels of ouabain-like factor were higher during sodium depletion ( acute : 338.8±17.4 and 402.7±22.8 pmol/L for baseline and low sodium , respectively , P < 0.01 ; chronic : 320.4±32.0 versus 481.0±48.1 pmol/L , P = 0.01 ) . No significant change in plasma ouabain-like factor was observed after a 2-hour saline infusion ( 333.4±23.9 pmol/L ) or controlled sodium ( 402.1±34.9 pmol/L ) . When patients were divided into salt-sensitive or salt-resistant groups , no differences in plasma ouabain-like factor were observed in the 2 groups at baseline or in response to the 2 protocol s : salt resistant ( n=69 , 340.1±25.9 pmol/L ) versus salt sensitive ( n=69 , 337.4±23.6 pmol/L ) and chronic salt resistant ( n=11 , 336.0±53.2 ) versus salt sensitive ( n=9 , 301.1±331.4 pmol/L ) . However , circulating ouabain-like factor was increased by sodium depletion in both groups . These results demonstrate that circulating ouabain-like factor is raised specifically by maneuvers that promote the loss of body sodium . Acute expansion of body fluids with isotonic saline is not a stimulus to plasma ouabain-like factor . Moreover , basal levels of plasma ouabain-like factor do not differ among patients with salt-sensitive or salt-resistant hypertension . Taken together , these new results suggest that ouabain-like factor is involved in the adaptation of humans to sodium depletion and argue against the hypothesis that ouabain-like factor is a natriuretic hormone Evidence suggests that dietary salt reduction similar to diuretic therapy may adversely affect lipid and glucose metabolism . We studied 147 non-obese normotensive subjects ( 60 females and 87 males ) aged 19 - 78 years who entered a single-blind crossover trial and were r and omly assigned to a low salt diet of 20 mmol or a high salt diet of 300 mmol sodium per day , for 7 days each . Sodium restriction lowered mean arterial blood pressure ( MAP ) by a mean of 7.5 mmHg in 17 % ( salt-sensitive ) , had no hemodynamic effect in 67 % ( salt-resistant ) and raised MAP by a mean of 6 mmHg in 16 % of the subjects ( reverse reactors ) . With dietary salt restriction serum total- and LDL-cholesterol as well as serum insulin and uric acid concentrations increased significantly in all three groups . The largest increases in total ( 10 % ) and LDL- ( 12 % ) cholesterol occurred in the reverse reactors . Salt-sensitives had significant higher lipoprotein(a ) values than the other two groups . Salt-restriction had no significant effect on this parameter . Plasma renin activity , as well as plasma aldosterone and noradrenaline concentrations rose in all three groups during the low salt diet , the largest increases being observed in the reverse reactors . Short-term sodium restriction in normotensive adults has unfavourable effects on lipid and glucose metabolism , especially in subjects who do not derive hemodynamic benefit . Further studies are necessary to examine the effects of more moderate salt reduction for longer periods on the risk factor profile for cardiovascular disease before a low salt diet can be regarded as a safe public health measure for the general population Thirty five subjects with both parents in the top third of their age specific blood pressure distributions and 31 subjects with both parents in the bottom third of their blood pressure distributions restricted their intake of sodium for eight weeks while taking part in a double blind , r and omised crossover trial of supplements of sodium and placebo . A comparison of two periods of four weeks at different intakes of sodium showed no differences in blood pressure in either the groups as a whole or the subgroups who complied best with the diet and tablets . In the compliant subgroups mean urinary sodium excretions were above 120 mmol(mEq ) and below 50 mmol/day . The study provides evidence against the hypothesis that people with a family history of high blood pressure are more susceptible in their blood pressure response to dietary sodium Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension . To test the hypothesis that salt sensitivity in humans may be associated with abnormal acid-base homeostasis , we performed arterial blood gas analyses in young ( 20 - 31 years old ) normotensive subjects ( n = 40 ) who were placed on a low salt diet ( 20 mmol NaCl/day ) for 2 weeks with either 200 mmol sodium chloride or placebo added to the low salt diet for 1 week each in a r and omized , single-blind crossover order . Furthermore , a subset of the subjects ( seven salt-sensitive and eight salt-resistant ) received 200 mmol sodium/day as the citrate salt as a supplement to the low salt diet for a third week . During each regimen , blood pressure as well as arterial pH and bicarbonate levels were measured . Salt sensitivity was defined as a significant drop in mean arterial pressure greater than 3 mm Hg ( mean of 30 readings taken during each diet , p less than 0.05 ) while the subject was on the low salt diet . According to this definition , 16 subjects were salt-sensitive and 24 salt-resistant . During the high sodium chloride regimen , arterial pH and bicarbonate levels were significantly lower in the salt-sensitive than in the salt-resistant group ( p less than 0.0001 ) . The increase in blood pressure caused by sodium chloride correlated inversely to the arterial pH ( r = -0.57 , p = 0.0002 ) and bicarbonate levels ( r = -0.52 , p = 0.0007 ) during the high salt diet . Sodium chloride increased mean arterial blood pressure in the salt-sensitive subjects ; sodium citrate did not . Sodium citrate led to an increase in pH and bicarbonate levels in both groups . Our finding that a sodium chloride-induced rise in blood pressure is associated with lower arterial plasma pH and bicarbonate levels points to an abnormality in renal acid-base regulation in salt-sensitive subjects Nine white and 13 black hypertensive patients with normal serum creatinine were r and omized to receive either 2 weeks of a low-salt ( 40 mEq Na+/d ) or high-salt ( 200 mEq Na+/d ) diet followed by 2 weeks of the other diet separated by a 1-week washout on their regular diet . The entire study was conducted in an outpatient setting with intensive dietary instruction and monitoring of blood pressure and 24-hour collection s of urine for analysis . Urine electrolyte measurement showed that the patients were able to achieve only a modestly reduced ( 100 + /- 14 mEq Na+/24 h [ mean + /- SEM ] ) low-salt diet as out patients , while the higher-salt diet ( 236 + /- 22 mEq Na+/24 h ) was more easily achieved . Eleven patients ( 8 black , 3 white ) were classified as modestly salt sensitive on the basis of an increase or decrease in mean arterial pressure of > or = 3 mm Hg going from lower- to high- or high- to lower-salt diets , respectively . In the salt-sensitive patients , the increase in dietary salt intake increased glomerular filtration rate by 29 % ( 71.2 + /- 6.6 to 85.8 + /- 7.3 mL.min-1.1.73 m2 , P = .05 ) , with no significant change in renal plasma flow ( 412.7 + /- 36.4 to 399.6 + /- 27.8 mL.min-1.1.73 m2 ) . There were no changes in these parameters in the salt-resistant patients . ( ABSTRACT TRUNCATED AT 250 WORDS An increase of some serum lipid fractions has been documented in normotensive healthy volunteers and patients with essential hypertension during acute drastic restriction of salt intake . To clarify the potential role of vasopressor systems , particularly the sympathetic system , in the lipid changes induced by salt restriction , we compared fasting serum lipids , glucose , insulin , and C-peptide levels in 16 normotensive healthy volunteers during 7 days of high ( 200 mmol/day ) and 7 days of low ( 20 mmol/day ) salt intake . The individuals were examined on either placebo or on the alpha 1-adrenergic blocker doxazosin ( 2 mg/day ) . The study was carried out using a single blind parallel group r and om order design with two arms of treatment . In the volunteers on placebo , total cholesterol ( corrected for hemoconcentration ) was significantly higher ( P < .01 ) during low salt intake . The same was true for LDL-cholesterol , whereas HDL-cholesterol and triglycerides did not change with salt intake . The lipid changes , and , in parallel , the changes of hemoconcentration indicators , were more pronounced after 2 days than after 7 days of low salt intake . The rise of total and LDL-cholesterol on low salt was blunted after alpha 1-adrenergic blockade with doxazosin . Fasting glycemia was similar on low salt and high salt , respectively , but in placebo treated volunteers , C-peptide levels were significantly ( P < .01 ) higher on low , rather than high , salt intake . alpha 1-Adrenergic blockade with doxazosin attenuated the rise of C-peptide levels on low salt . The results confirm previous findings that levels of total cholesterol and LDL-cholesterol change inversely with salt intake in normotensive healthy volunteers . ( ABSTRACT TRUNCATED AT 250 WORDS 31 patients with a diastolic blood-pressure between 95 and 109 mm Hg have been treated for two years with a regimen involving a moderate restriction of salt in the diet . The results are compared with those in a control group and in a drug-treated group . Salt restriction has reduced the diastolic blood-pressure by 7.3+/-1.6 mm Hg , a result similar to that in patients treated with antihypertensive drugs . In the untreated group the diastolic blood-pressure rose by 1.8+/-1.1 mm Hg . Most patients did not achieve the desired amount of salt restriction and a stricter adherence to the diet might have caused further falls in blood-pressure . Excessive salt intake is probably a major cause of the epidemic of hypertension in " civilised " countries and a reduction in salt intake may help to control the epidemic . In persons with a diastolic blood-pressure between 90 and 105 mm Hg salt restriction should be tried before drugs We have previously reported that modest dietary sodium restriction , as advocated in management guidelines for diabetes , may reduce insulin sensitivity . It has since been suggested that this effect may be mediated via cross-talk between insulin and angiotensin II (AII)-stimulated intracellular second messengers . In order to assess the effect of 5 days of modest sodium restriction ( to < 80 mmol/day target sodium intake ) on insulin sensitivity , 15 healthy males underwent a double-blind , placebo-controlled , r and omized , cross-over euglycaemic hyperinsulinaemic clamp study . One phase was supplemented with sodium tablets and the other with matched placebo . Insulin sensitivity ( M ) was reduced during dietary sodium restriction [ median M value , 10.2 mg/kg per min ( interquartile range 9.50 - 13.85 ) versus 12.8 mg/kg per min ( interquartile range 9.60 - 14.30 ) , P < 0.05 ] . To eluci date potential mechanisms that may explain this observation , we investigated the effect of AII on insulin action in isolated adipocytes obtained from healthy females . No effect of AII on insulin-mediated glucose transport or suppression of lipolysis was observed . In conclusion , despite the observation that dietary sodium restriction was associated with a median 15 % reduction in insulin sensitivity , we found no evidence of a direct effect of AII on insulin action in human adipocytes OBJECTIVE --To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent ( type II ) diabetes . DESIGN --R and omised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet , followed by r and omised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction . SETTING -- Patients attending diabetic outpatient clinic of city hospital . PATIENTS --Thirty four patients with established type II diabetes complicated by mild hypertension ( systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions ) . Patients already taking antihypertensive agents ( but not diuretics ) not barred from study provided that criteria for mild hypertension still met . Conditions precluding patients from study were diabetic or hypertensive nephropathy , cardiac failure , and pregnancy . INTERVENTIONS --After run in phase with recordings at seven weeks , three weeks , and time zero patients were allocated at r and om to receive moderate dietary sodium restriction for three months ( n = 17 ) or to continue with usual diabetic diet . Subsequently nine patients in sodium restriction group continued with regimen for a further two months , during which they completed a r and omised double blind crossover trial of sustained release preparation of sodium ( Slow Sodium 80 mmol daily ) for one month versus matching placebo for one month . END POINT -- Reduction in blood pressure in type II diabetics with mild hypertension . MEASUREMENTS AND MAIN RESULTS --Supine and erect blood pressure , body weight , and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies . After parallel group study sodium restriction group showed significant reduction in systolic blood pressure ( supine 19.2 mm Hg , erect 21.4 mm Hg ; p less than 0.001 ) and mean daily urinary sodium excretion ( mean reduction 60 mmol/24 h ) . There were no appreciable changes in weight , diabetic control , or diastolic pressure . No significant changes occurred in controls . In double blind crossover study mean supine systolic blood pressure rose significantly ( p less than 0.005 ) during sodium supplementation ( to 171 mm Hg ) compared with value after three months of sodium restriction alone ( 159.9 mm Hg ) and after one month of placebo ( 161.8 mm Hg ) . CONCLUSIONS --Moderate dietary restriction of sodium has a definite hypotensive effect , which may be useful in mild hypertension of type II diabetes BACKGROUND Hypertension is a major modifiable risk factor , and while sodium restriction in hypertensive patients appears effective , its role in normotensive individuals remains unclear . We assessed the effect of a low vs. high-sodium diet on blood pressure in normotensive Indo-Asian adults . METHODS A r and omized , controlled , crossover trial was conducted on 200 normotensive subjects r and omly selected from the general population in Karachi , Pakistan . Participants were r and omized to either a low ( 20 mEq/day ) or a high-sodium diet ( 220 mEq/day ) for 1 week , followed by 1 week of washout , then the alternate diet for 1 week . The primary outcome was difference in systolic blood pressure ( SBP ) measured at the end of each phase in the overall population . RESULTS Mean ( 95 % confidence interval ) decline in 24-h urinary sodium excretion was 81.0 ( 69.6 - 92.4 ) mEq/day ( P < 0.001 ) , and in SBP was 1 (0 - 3)mm Hg ( P = 0.17 ) between high and low-sodium phase . A significant interaction was detected ( P = 0.001 ) between dietary sodium and baseline SBP with a greater adjusted mean ( 95 % confidence interval ) decline in SBP ( 6 (2 - 9)mm Hg ) among participants with high-normal SBP ( 130 - 139 mm Hg ) and no significant change ( -1(-2 to 1 ) ) in those with normal baseline SBP ( < 130 mm Hg ) , respectively . CONCLUSIONS Reducing sodium intake has a beneficial effect on blood pressure in Indo-Asians with high-normal SBP , at least in the short term . Given the ubiquity of high-normal blood pressure ( BP ) , and frank hypertension in this population , we argue that primary prevention strategies , targeted at use of discretionary sodium , should now be design ed and evaluated To study the effect of dietary salt restriction and supplementation on blood pressure of elderly subjects , we performed a r and omized , placebo-controlled , double-blind , crossover trial . Seven healthy subjects living in a long-term care facility , with a mean age of 85 and normal to borderline-hypertensive blood pressures , completed a 16-week protocol . During the double-blind cycles , subjects consumed either a low sodium ( 43 mmol/day ) or a high sodium diet ( 175 mmol/day ) for four weeks supplemented with placebo or salt capsules , with crossover to the other diet . Sitting diastolic blood pressure was significantly lower during the low sodium diet ( 69.86 mmHg + /- 3.80 vs 78.71 mmHg + /- 3.99 , P less than .01 ) , with all subjects showing decreases . Supine plasma renin activity and plasma aldosterone were significantly lower during the high sodium diet . Both low and high sodium diets were well-tolerated by subjects . Symptomatic postural hypotension and hyponatremia were not observed . We conclude that old-old subjects with borderline hypertension demonstrate salt-dependent increases in blood pressure . Without additional supportive studies , however , these results should not be generalized to any specific cohort of elderly individuals We studied , under outpatient conditions , nine patients with autosomal dominant polycystic kidney disease who were hypertensive on their usual diet , and nine normotensive healthy prob and s. The subjects were examined in r and om order on the 7th day after equilibration on a low-sodium diet ( 20 mmol/day ) and again on the 7th day after equilibration on the same diet but with added sodium to yield a final intake of 200 mmol/day ( or vice versa ) . Blood pressure was monitored non-invasively for 2 h at 4-min intervals using an automatic system . In healthy prob and s , mean arterial pressure ( MAP ) was similar on the low- and the high-sodium diets ( 92.7 versus 91.9 mmHg ) . In hypertensive patients , a significant ( P less than 0.02 ) increase in mean MAP ( 107.2 versus 111.2 mmHg ) and in systolic blood pressure ( 140.6 versus 148.7 mmHg ) was observed irrespective of whether the glomerular filtration rate ( GFR ) was normal or reduced . The natriuresis pressure curve showed an upward shift ( re setting ) and a positive slope ( sodium sensitivity ) . Patients with a reduced GFR as shown by inulin clearance differed from prob and s and patients with a normal GFR , by showing greater proportional changes in GFR and body weight . In hypertensive patients , atrial natriuretic factor ( ANF ) levels were higher at baseline and showed an exaggerated response to sodium loading . Changes in angiotensin II ( Ang II ) or in Ang II binding sites on platelets were similar in patients and controls and changed appropriately with the sodium intake . These data show a re setting of the natriuresis-blood pressure relationship and an increased blood pressure sensitivity to sodium in hypertensive patients with adult , dominant , polycystic kidney disease Studies have shown that patients with compensated heart failure ( HF ) receiving high diuretic doses associated with normal sodium diet and fluid intake restrictions demonstrated significant reductions in readmissions and mortality compared with those who received low-sodium diets , and over a 6-month observation period , a reduction in neurohormonal activation was also observed . The aim of this study was to evaluate the effects of different sodium diets associated with different diuretic doses and different levels of fluid intake on hospital readmissions and neurohormonal changes after 6-month follow-up in patients with compensated HF . Four hundred ten consecutive patients with compensated HF ( New York Heart Association class II to IV ) aged 53 to 86 years , with ejection fractions < 35 % and serum creatinine < 2 mg/dl , were r and omized into 8 groups : group A ( n = 52 ) : 1,000 ml/day of fluid intake , 120 mmol/day , and 250 mg furosemide twice daily ; group B ( n = 51 ) : 1,000 ml/day of fluid intake , 120 mmol/day , and 125 mg furosemide twice daily ; group C ( n = 51 ) : 1,000 ml/day fluid intake , 80 mmol/day , and 250 mg furosemide twice daily ; group D ( n = 51 ) : 1,000 ml/day fluid intake , 80 mmol/day , and 125 mg furosemide twice daily ; group E ( n = 52 ) : 2,000 ml/day fluid intake , 120 mmol/day , and 250 mg furosemide twice daily ; group F ( n = 50 ) : 2,000 ml/day fluid intake , 120 mmol/day , and 125 mg furosemide twice daily ; group G ( n = 52 ) : 2,000 ml/day fluid intake , 80 mmol/day , and 250 mg furosemide twice daily ; and group H ( n = 51 ) : 2,000 ml/day fluid intake , 80 mmol/day , and 125 mg furosemide twice daily . All patients received the treatments > or=30 days after discharge and for 180 days afterward . Signs of HF , body weight , blood pressure , heart rate , laboratory parameters , electrocardiograms , echocardiograms , brain natriuretic peptide , aldosterone , and plasma renin activity were examined at baseline and 180 days later . Group A showed the best results , with a significant reduction ( p < 0.001 ) in readmissions , brain natriuretic peptide , aldosterone , and plasma renin activity compared with the other groups during follow-up ( p < 0.001 ) . In conclusion , these data suggest that the combination of a normal-sodium diet with high diuretic doses and fluid intake restriction , compared with different combinations of sodium diets with more modest fluid intake restrictions and conventional diuretic doses , leads to reductions in readmissions , neurohormonal activation , and renal dysfunction Recent studies have shown that insulin has a direct vasodilator effect and that vascular sensitivity to insulin is impaired in hypertension . How the vasodilator effect of insulin is regulated physiologically is unknown . It has been appreciated that salt restriction may have adverse effects on glucose and lipid metabolism — processes regulated by insulin . To determine whether dietary salt restriction might affect vascular sensitivity to insulin , we studied 13 subjects ( including eight borderline hypertensive subjects and five normotensive subjects ) after 1 week of a normal sodium diet ( 240 mEq/day ) and after 1 week of a low‐sodium diet ( 20 mEq/day ) with a r and omized , double‐blind crossover design Blood pressure responses to 1 week of low ( 20 mmol sodium/day ) and high ( 300 mmol sodium/day ) salt intake were investigated in a double-blind , r and omized study in 46 white , nonobese subjects with essential hypertension ( 13 women , 33 men ; mean age 45.3 + /- 2.2 years , age range 25 to 80 years ) . The individuals were classified as salt-sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high salt intake , as salt-resistant when mean arterial blood pressure changed by less than 5 mm Hg , and as " counter-regulators " when mean arterial blood pressure fell by at least 5 mm Hg during the high salt diet . Mean arterial blood pressure of all subjects taken together increased from 101.9 + /- 1.4 mm Hg during salt restriction to 103.7 + /- 1.5 mm Hg ( P < .05 ) during salt loading . Eleven subjects ( 23.9 % ) were classified as salt-sensitive , 27 ( 58.7 % ) as salt-resistant , and 8 ( 17.4 % ) as counter-regulators . Multiple regression analysis revealed that age , but not baseline blood pressure , sex , body mass index , or family history of hypertension contributed significantly to the change in blood pressure following the diets . Ten of the 11 salt-sensitive subjects were older than the median age of 45 years . In salt-sensitive , as compared to salt-resistant , hypertensive subjects , creatinine clearance was lower and plasma renin activity was suppressed at baseline as well as during low and high salt intake . In contrast , plasma concentrations of norepinephrine and atrial natriuretic peptide were elevated in salt-sensitive subjects . These differences between the groups appeared , at least partially , to be age-related . ( ABSTRACT TRUNCATED AT 250 WORDS Sodium intake has profound effects on systemic and renal sympathetic activity , but its effects on sympathetic activity in skeletal muscle vascular beds , a site at which local regulatory mechanisms could alter vascular tone directly , are unclear Data from 13 r and omised trials on the effect of sodium restriction on blood pressure were analysed . The hypotensive effect of sodium restriction was found to be small and restricted largely to systolic blood pressure , which fell by an average of 3.6 mm Hg ( range 0.5 - 10.0 mm Hg ) . The reduction increased with age and in those with higher blood pressure . Sodium restriction therefore seems to be of limited use in those who are most eligible for non-pharmacological treatment of high blood pressure -- namely , young patients with mild hypertension Hypertension remains the most common cardiovascular risk factor in developing countries , yet the majority of patients have no access to pharmacological therapy . Population -wide preventive strategies , such as salt restriction , are an attractive alternative , but experience in re source -poor setting s is limited . To address this question , we conducted a r and omized crossover study of salt restriction in adults living in Nigeria and Jamaica in order to estimate the mean blood pressure ( BP ) response . After a 4-week run-in period to determine willingness to adhere to a low-salt diet , 56 Jamaicans and 58 Nigerians completed an 8-week crossover study of low-salt and high-salt intake . Baseline BPs were in the normotensive range ( systolic=125 mmHg in Jamaica , 114 mmHg in Nigeria ) . Baseline urinary sodium excretion was 86.8 and 125.6 mEq/day in Nigeria and Jamaica , respectively . The mean difference between urinary sodium excretion at baseline and at the end of the 3-week low-sodium phase was 33.6 mEq/day in Nigeria and 57.5 mEq/day in Jamaica . During the high-sodium phase , mean change in urinary sodium excretion from baseline to week 3 was 35.0 and 5.5 mEq/day in Nigeria and Jamaica , respectively . The mean change in systolic BP ( ‘ high ’ vs ‘ low ’ sodium phase ) was approximately 5 mmHg in both groups . This study suggests that the efficacy of sodium reduction in developing countries equals those noted in more affluent cultures . If promoted on a wide scale , sodium reduction could be used to treat persons with established hypertension , and more importantly , to prevent age-related increases in BP in poor communities Abstract —We evaluated the effect on serum lipids of sodium intake in 2 diets . Participants were r and omly assigned to a typical American control diet or the Dietary Approaches to Stop Hypertension ( DASH ) diet , each prepared with 3 levels of sodium ( targeted at 50 , 100 , and 150 mmol/d per 2100 kcal ) . The DASH diet is increased in fruits , vegetables , and low-fat dairy products and is reduced in saturated and total fat . Within assigned diet , participants ate each sodium level for 30 days . The order of sodium intake was r and om . Participants were 390 adults , age 22 years or older , with blood pressure of 120 to 159 mm Hg systolic and 80 to 95 mm Hg diastolic . Serum lipids were measured at baseline and at the end of each sodium period . Within each diet , sodium intake did not significantly affect serum total cholesterol , LDL cholesterol , HDL cholesterol , or triglycerides . On the control diet , the ratio of total cholesterol-to-HDL cholesterol increased by 2 % from 4.53 on higher sodium to 4.63 on lower sodium intake ( P = 0.04 ) . On the DASH diet , sodium intake did not affect this ratio . There was no dose-response of sodium intake on serum lipids or the cholesterol ratio in either diet . At each sodium level , total cholesterol , LDL cholesterol , and HDL cholesterol were lower on the DASH diet versus the typical American diet . There were no significant interactions between the effects of sodium and the DASH diet on serum lipids . In conclusion , changes in dietary sodium intake over the range of 50 to 150 mmol/d did not affect blood lipid concentrations Using a cross-over type setup with 4 periods of 1 month each in 22 patients with mild , mostly essential hypertension , the antihypertensive action of the following therapeutic regimens were compared : ( 1 ) a regular diet and placebo ( period RP ) , ( 2 ) a regular diet and 100 mg . hydrochlorothiazide and 100 mg . spironolactone ( period RD ) , ( 3 ) a moderate sodium restriction and placebo ( LP period ) , and ( 4 ) this diet together with the same diuretics ( period LD ) . The diuretics or placebo were administered on a double blind basis , while the sodium restriction or regular sodium diet was prescribed in an open , but r and omized system . The 24 hour urinary sodium averaged 191.1 ± 61.2 mEq . during the RP period and 92.8 ± 41.8 mEq . during the LP period . Compared to the RP period , the reduction in home blood pressures was more important with diuretics alone ( 16.18.1 mm . Hg ) than with this moderate sodium restriction alone ( 7.74.4 mm . Hg ) , while the combination of both produced a statistically significantly ( p < 0.005 ) higher blood pressure reduction ( 20.710.8 mm . Hg ) . Not only the diuretics but also the sodium restriction increased the serum uric acid , and this could be related to the decreased urinary uric acid clearance . A significant ( p < 0.001 ) correlation ( r = 0.66 ) was obtained between the decrease in systolic blood pressure ( expressed in mm . Hg ) produced by the sodium restriction ( y ) and the decrease in 24 hour urinary sodium excretion ( expressed in mEq . ) produced by the same diet : y=−6.58 + 0.163x These data suggest that a reduction of the daily NaCl intake from 10 to 5 Gm . could produce a decrease of blood pressure of about 105 mm . Hg 1 . Responses of adrenomedullin to acute and chronic salt loading were examined in normotensive and hypertensive subjects . 2 . In the acute salt load study , isotonic saline ( 50 ml/kg for 1 h ) was intravenously infused into nine normotensive subjects and 11 patients with essential hypertension . Plasma adrenomedullin was higher in hypertensive than in normotensive subjects but was unchanged by saline infusion in either the normotensive ( before infusion , 2.4 + /- 0.2 fmol/ml ; after infusion , 2.4 + /- 0.1 fmol/ml ) or hypertensive ( before infusion , 3.0 + /- 0.1 fmol/ml ; after infusion , 2.9 + /- 0.2 fmol/ml ) group , while renin was suppressed and atrial natriuretic peptide was markedly increased . Plasma endothelin was not affected either . 3 . In the chronic salt load study , seven normotensive subjects and 23 patients with essential hypertension underwent two 7-day periods of 30 and 260 mmol/day sodium intake . Depending on the blood pressure change , 13 hypertensive subjects were classified as salt-resistant and 10 as salt-sensitive . Salt-sensitive hypertensive subjects had suppressed plasma renin activity even during low salt intake . Plasma adrenomedullin or endothelin were not affected by the salt intake changes in any group ; however , the high salt intake increased atrial natriuretic peptide in all groups . 4 . These data indicate that the circulating level of adrenomedullin is not changed by either acute or chronic salt loading in normotensive subjects and patients with essential hypertension 57 couples living in two communities of North Karelia , aged 30 - 50 years , were r and omly allocated to three groups . After a 2-week baseline period group I followed a diet low in fat ( 23 % of energy ) with a high polyunsaturated/saturated ( P/S ) ratio ( 1 . 0 ) , group II reduced daily salt intake from 192 mmol to 77 mmol , and group III ( control group ) continued the usual diet . After the 6-week intervention period groups I and II reverted to their usual diets . In group I systolic blood pressure declined from 138 . 4 to 129 . 5 mm Hg and diastolic blood pressure from 88 . 9 to 81 . 3 mm Hg during the intervention period ; the values rose during switch-back . The fall was greater among hypertensive than among normotensive subjects . In groups II and III the mean blood pressure changed very little during the study The effects of changing sodium balance on blood pressure ( BP ) and erythrocyte sodium transport were investigated in normotensive first-degree relatives of hypertensive patients and control subjects r and omised to receive low and high salt diets for two weeks , separated by a two week washout period . Changing from high to low salt intake produced a significant fall in st and ing diastolic pressure ( DBP ) in control subjects but not in the offspring of hypertensive patients . In both groups erythrocyte sodium efflux was not changed significantly by either manoeuvre , but the relatives had a significantly higher ouabain insensitive sodium efflux rate constant on both the low and the high salt diet compared to the controls ( P less than 0.05 ) . These results are not in keeping with the hypothesis which suggests the release of a humoral sodium pump inhibitor in response to sodium loading but lend support to the view that there is a disturbance of membrane permeability to sodium in subjects genetically prone to hypertension The effects of severe and moderate sodium restriction on blood pressure and serum lipids were studied in nonobese normotensive adults . Subjects ( n = 163 ) were given a low ( 20 mmol Na/d ) and high ( 300 mmol Na/d ) salt diet for 1 week each in r and om order . Of these subjects , 25 were selected to participate in a second study with moderate salt restriction ( 85 mmol na/d ) or " normal " sodium diet ( 200 mmol Na/d ) given for 4 weeks each in r and om order . After severe salt restriction , 19 % of the 163 subjects had a significant decrease in blood pressure ( salt-sensitive ) , 15 % showed a significant rise ( counter-regulator ) , and 66 % exhibited no change ( salt-resistant ) . Severe sodium restriction increased serum total and low density lipoprotein ( LDL ) cholesterol and triglycerides . After correction for hematocrit , the changes in blood lipids remained significant in the counter regulators only . After moderate salt restriction , serum lipid concentrations and blood pressure did not change |
12,444 | 26,814,278 | The existing literature suggests that classical conditioning can amplify pain .
No conclusions can be drawn about whether or not classical conditioning can elicit pain . | BACKGROUND Clinical scenarios of repeated pain usually involve both nociceptive and non-nociceptive input .
It is likely that associations between these stimuli are learned over time .
Such learning may underlie subsequent amplification of pain , or evocation of pain in the absence of nociception .
METHODS We undertook a systematic review and meta- analysis to evaluate the evidence that allodynia or hyperalgesia can be a classically conditioned response . | & NA ; Conditioning procedures are used in many placebo studies because evidence suggests that conditioning‐related placebo responses are usually more robust than those induced by verbal suggestions alone . However , it has not been shown whether there is a causal relation between the number of conditioning trials and the resistance to extinction of placebo and nocebo responses . Here we test the effects of either one or four sessions of conditioning on the modulation of both non‐painful and painful stimuli delivered to the dorsum of the foot . Placebo and nocebo manipulations were obtained by pairing green or red light to a series of stimuli that were made lower or higher with respect to a yellow light associated with a series of control stimuli . Subjects were told that the lights would indicate a treatment that would reduce or increase non‐painful and painful stimuli to the foot . They were r and omly assigned to either Group 1 or 2 . Group 1 underwent one session of conditioning and Group 2 received four sessions of conditioning . We found that one session of conditioning ( Group 1 ) induced nocebo responses , but not placebo responses in no pain condition . After one session of conditioning , we observed both nocebo and placebo responses to painful stimulation . However , these effects extinguished over time . Conversely , four sessions of conditioning ( Group 2 ) induced robust placebo and nocebo responses to both non‐painful and painful stimuli that persisted over the entire experiment . These findings suggest that the strength of learning may be clinical ly important for producing long‐lasting placebo effects The placebo and nocebo effect is believed to be mediated by both cognitive and conditioning mechanisms , although little is known about their role in different circumstances . In this study , we first analyzed the effects of opposing verbal suggestions on experimental ischemic arm pain in healthy volunteers and on motor performance in Parkinsonian patients and found that verbally induced expectations of analgesia/hyperalgesia and motor improvement/worsening antagonized completely the effects of a conditioning procedure . We also measured the effects of opposing verbal suggestions on hormonal secretion and found that verbally induced expectations of increase/decrease of growth hormone ( GH ) and cortisol did not have any effect on the secretion of these hormones . However , if a preconditioning was performed with sumatriptan , a 5-HT1B/1D agonist that stimulates GH and inhibits cortisol secretion , a significant increase of GH and decrease of cortisol plasma concentrations were found after placebo administration , although opposite verbal suggestions were given . These findings indicate that verbally induced expectations have no effect on hormonal secretion , whereas they affect pain and motor performance . This suggests that placebo responses are mediated by conditioning when unconscious physiological functions such as hormonal secretion are involved , whereas they are mediated by expectation when conscious physiological processes such as pain and motor performance come into play , even though a conditioning procedure is performed Learning processes such as respondent or Pavlovian conditioning are believed to play an important role in the development of chronic pain , however , their influence on the inhibition of pain has so far not been assessed in humans . The purpose of this study was the demonstration of Pavlovian conditioning of stress-induced analgesia in humans and the determination of its opioid mediation . In a differential classical conditioning paradigm two different auditory stimuli served as conditioned stimuli and mental arithmetic plus white noise as unconditioned stimulus . Subsequent to four conditioning trials naloxone or placebo was applied in a double-blind fashion on two test days . Both pain threshold and pain tolerance showed conditioned stress-induced analgesia . Pain tolerance was affected by naloxone whereas pain threshold was not . The data of this study show that stress analgesia can be conditioned in humans and that it is at least partially mediated by the endogenous opioid system . Learning processes also influence pain inhibitory processes in humans and this effect might play a role in the development of chronic pain UNLABELLED Emotionally charged facial expressions ( happy , fear ) served as conditioned stimuli in a differential fear conditioning procedure . Expressions were presented in pseudo-r and om order on a computer monitor . For half of the participants , the fear expression was paired with an aversive electric stimulation ( UCS ) , whereas the happy expression was unpaired . The other participants had the opposite pairing . To assess the influence of conditioned fear on pain , expressions were shown again in the absence of the UCS and pain threshold was assessed during each expression . The latency of finger withdrawal from a radiant heat device was used to index pain threshold . Skin conductance response ( SCR ) and self-reported emotion were measured to assess fear conditioning . Consistent with preparedness theory , differential fear conditioning was only present when the fear expression was paired with the UCS . Moreover , pain threshold was only influenced by fear conditioning in persons for whom the fear expression was paired with the UCS . Specifically , finger withdrawal latencies were lower ( suggesting hyperalgesia ) during the fear expression than during the happy expression ; an effect that was not present before CS-UCS pairing . This work suggests that some stimuli are more readily associated with an aversive event and can lead to pain enhancement . PERSPECTIVE Although preliminary , these results suggest that fear-relevant environmental stimuli ( including facial expressions ) may provide important environmental cues during aversive events that influence the level of pain experienced We investigated the mechanisms underlying the activation of endogenous opioids in placebo analgesia by using the model of human experimental ischemic arm pain . Different types of placebo analgesic responses were evoked by means of cognitive expectation cues , drug conditioning , or a combination of both . Drug conditioning was performed by means of either the opioid agonist morphine hydrochloride or the nonopioid ketorolac tromethamine . Expectation cues produced placebo responses that were completely blocked by the opioid antagonist naloxone . Expectation cues together with morphine conditioning produced placebo responses that were completely antagonized by naloxone . Morphine conditioning alone ( without expectation cues ) induced a naloxone-reversible placebo effect . By contrast , ketorolac conditioning together with expectation cues elicited a placebo effect that was blocked by naloxone only partially . Ketorolac conditioning alone produced placebo responses that were naloxone-insensitive . Therefore , we evoked different types of placebo responses that were either naloxone-reversible or partially naloxone-reversible or , otherwise , naloxone-insensitive , depending on the procedure used to evoke the placebo response . These findings show that cognitive factors and conditioning are balanced in different ways in placebo analgesia , and this balance is crucial for the activation of opioid or nonopioid systems . Expectation triggers endogenous opioids , whereas conditioning activates specific subsystems . In fact , if conditioning is performed with opioids , placebo analgesia is mediated via opioid receptors , if conditioning is performed with nonopioid drugs , other nonopioid mechanisms result to be involved It is common clinical experience that anxiety about pain can exacerbate the pain sensation . Using event-related functional magnetic resonance imaging ( FMRI ) , we compared activation responses to noxious thermal stimulation while perceived pain intensity was manipulated by changes in either physical intensity or induced anxiety . One visual signal , which reliably predicted noxious stimulation of moderate intensity , came to evoke low anxiety about the impending pain . Another visual signal was followed by the same , moderate-intensity stimulation on most of the trials , but occasionally by discriminably stronger noxious stimuli , and came to evoke higher anxiety . We found that the entorhinal cortex of the hippocampal formation responded differentially to identical noxious stimuli , dependent on whether the perceived pain intensity was enhanced by pain-relevant anxiety . During this emotional pain modulation , entorhinal responses predicted activity in closely connected , affective ( perigenual cingulate ) , and intensity coding ( mid-insula ) areas . Our finding suggests that accurate preparatory information during medical and dental procedures alleviates pain by disengaging the hippocampus . It supports the proposal that during anxiety , the hippocampal formation amplifies aversive events to prime behavioral responses that are adaptive to the worst possible outcome Abstract Animal studies suggest that fear inhibits pain whereas anxiety enhances it ; however it is unclear whether these effects generalize to humans . The present study examined the effects of experimentally induced fear and anxiety on radiant heat pain thresholds . Sixty male and female human subjects were r and omly assigned to 1 of 3 emotion induction conditions : ( 1 ) fear , induced by exposure to three brief shocks ; ( 2 ) anxiety , elicited by the threat of shock ; ( 3 ) neutral , with no intervention . Pain thresholds were tested before and after emotion induction . Results suggest that findings from animal studies extend to humans : fear result ed in decreased pain reactivity , while anxiety led to increased reactivity . Pain rating data indicated that participants used consistent subjective criteria to indicate pain thresholds . Both subjective and physiological indicators ( skin conductance level , heart rate ) confirmed that the treatment conditions produced the targeted emotional states . These results support the view that emotional states modulate human pain reactivity |
12,445 | 29,621,988 | As the acceptability curves shown , full-dose sorafenib was the optimal strategy at the accepted thresholds of WTP in these two countries .
Conclusions Dose-adjusted sorafenib may be cost-effective compared to full-dose sorafenib or TACE for advanced HCC patients .
However , when confining the comparisons between full-dose sorafenib and TACE , full-dose sorafenib was cost-effective for these patients , under the accepted thresholds of WTP | Background Sorafenib and transarterial chemoembolization ( TACE ) might both provide survival benefit for advanced hepatocellular carcinoma ( HCC ) .
Adopting either as a first-line therapy carries major cost and re source implication s. We aim ed to estimate the cost-effectiveness of sorafenib and TACE in advanced HCC . | PURPOSE This phase II study of sorafenib , an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases , assessed efficacy , toxicity , pharmacokinetics , and biomarkers in advanced hepatocellular carcinoma ( HCC ) patients . METHODS Patients with inoperable HCC , no prior systemic treatment , and Child-Pugh ( CP ) A or B , received continuous , oral sorafenib 400 mg bid in 4-week cycles . Tumor response was assessed every two cycles using modified WHO criteria . Sorafenib pharmacokinetics were measured in plasma sample s. Biomarker analysis included phosphorylated extracellular signal regulated kinase ( pERK ) in pretreatment biopsies ( immunohistochemistry ) and blood-cell RNA expression patterns in selected patients . RESULTS Of 137 patients treated ( male , 71 % ; median age , 69 years ) , 72 % had CP A , and 28 % had CP B. On the basis of independent assessment , three ( 2.2 % ) patients achieved a partial response , eight ( 5.8 % ) had a minor response , and 46 ( 33.6 % ) had stable disease for at least 16 weeks . Investigator-assessed median time to progression ( TTP ) was 4.2 months , and median overall survival was 9.2 months . Grade 3/4 drug-related toxicities included fatigue ( 9.5 % ) , diarrhea ( 8.0 % ) , and h and -foot skin reaction ( 5.1 % ) . There were no significant pharmacokinetic differences between CP A and B patients . Pretreatment tumor pERK levels correlated with TTP . A panel of 18 expressed genes was identified that distinguished " nonprogressors " from " progressors " with an estimated 100 % accuracy . CONCLUSION Although single-agent sorafenib has modest efficacy in HCC , the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents UNLABELLED The prognosis of untreated patients with hepatocellular carcinoma ( HCC ) is heterogeneous , and survival data were mainly obtained from control arms of r and omized studies . Clinical practice data on this topic are urgently needed , so as to help plan studies and counsel patients . We assessed the prognosis of 600 untreated patients with HCC managed by the Italian Liver Cancer Group . Prognosis was evaluated by subdividing patients according to the Barcelona Clinic Liver Cancer ( BCLC ) classification . We also assessed the main demographic , clinical , and oncological determinants of survival in the subgroup of patients with advanced HCC ( BCLC C ) . Advanced ( BCLC C : n = 138 ; 23.0 % ) and end-stage HCC ( BCLC D ; n = 210 ; 35.0 % ) represented the majority of patients . Overall median survival was 9 months , and the principal cause of death was tumor progression ( n = 279 ; 46.5 % ) . Patients ' median survival progressively and significantly decreased as BCLC stage worsened ( BCLC 0 : 38 months ; BCLC A : 25 months ; BCLC B : 10 months ; BCLC C : 7 months ; BCLC D : 6 months ; P < 0.0001 ) . Female gender ( hazard ratio [ HR ] = 0.55 ; 95 % confidence interval [ CI ] = 0.33 - 0.90 ; P = 0.018 ) , ascites ( HR = 1.81 ; 95 % CI = 1.21 - 2.71 ; P = 0.004 ) , and multinodular ( > 3 ) HCC ( HR = 1.79 ; 95 % CI = 1.21 - 2.63 ; P = 0.003 ) were independent predictors of survival in patients with advanced HCC ( BCLC C ) . CONCLUSION BCLC adequately predicts the prognosis of untreated HCC patients . In untreated patients with advanced HCC , female gender , clinical decompensation of cirrhosis , and multinodular tumor are independent prognostic predictors and should be taken into account for patient stratification in future therapeutic studies This r and omized , controlled trial assessed the effect of transarterial embolization ( TAE ) ( without associated chemotherapy ) on the survival of patients with nonsurgical hepatocellular carcinoma ( HCC ) . Eighty consecutive patients were r and omized to treatment with embolization ( Group A , n = 40 ) , or to symptomatic treatment ( Group B , n = 40 ) , there being no differences between both groups regarding the degree of liver function impairment and tumor stage . Eighty‐two percent of the patients presented a self‐limited postembolization syndrome , without treatment‐related mortality . Fifty‐five percent of the treated cases exhibited a partial response , which result ed in a lower probability of tumor progression during follow‐up ( 57 % vs. 77 % at 1 year ; P < .005 ) . However , after a median follow‐up of 24 months ( 30 deaths in each group ) , there are no differences in survival ( Group A : 49 % and 13 % ; Group B : 50 % and 27 % , at 2 and 4 years , respectively ; P = .72 ) . The absence of differences was maintained even when dividing patients according to Child‐Pugh 's grade , Okuda stage , or performance status test ( PST ) . Furthermore , there were no differences in the probability of complications or in the need of hospital admissions . In conclusion , TAE has a marked antitumoral effect associated to a slower growth of the tumor , but it does not improve the survival of patients with nonsurgical HCC OBJECTIVES : Chronic liver disease ( CLD ) is an important cause of morbidity and mortality , but the epidemiology is not well described . We conducted prospect i ve population -based surveillance to estimate newly diagnosed CLD incidence , characterize etiology distribution , and determine disease stage . METHODS : We identified cases of CLD newly diagnosed during 1999–2001 among adult county residents seen in any gastroenterology practice in New Haven County , Connecticut ; Multnomah County , Oregon ; and Northern California Kaiser Permanente Medical Care Program ( KPMCP , Oakl and , California [ total population 1.48 million ] ) . We defined CLD as abnormal liver tests of at least 6 months ' duration or pathologic , clinical , or radiologic evidence of CLD . Consenting patients were interviewed , a blood specimen obtained , and the medical record review ed . RESULTS : We identified 2,353 patients with newly diagnosed CLD ( 63.9 cases/100,000 population ) , including 1,225 hepatitis C patients ( 33.2 cases/100,000 ) . Men aged 45–54 yr had the highest hepatitis C incidence rate ( 111.3/100,000 ) . Among 1,040 enrolled patients , the median age was 48 yr ( range 19–86 yr ) . Hepatitis C , either alone ( 442 [ 42 % ] ) or in combination with alcohol-related liver disease ( ALD ) ( 228 [ 22 % ] ) , accounted for two-thirds of the cases . Other etiologies included nonalcoholic fatty liver disease ( NAFLD , 95 [ 9 % ] ) , ALD ( 82 [ 8 % ] ) , and hepatitis B ( 36 [ 3 % ] ) . Other identified etiologies each accounted for <3 % of the cases . A total of 184 patients ( 18 % ) presented with cirrhosis , including 44 % of patients with ALD . CONCLUSIONS : Extrapolating from this population -based surveillance network to the adult U.S. population , approximately 150,000 patients with CLD were diagnosed in gastroenterology practice s each year during 1999–2001 . Most patients had hepatitis C ; heavy alcohol consumption among these patients was common . Almost 20 % of patients , an estimated 30,000 per year , had cirrhosis at presentation . These results provide population -level baseline data to evaluate trends in identification of patients with CLD in gastroenterology practice BACKGROUND & AIMS The natural history of HCV-related compensated cirrhosis has been poorly investigated in Latin-American countries . Our study evaluated mortality and clinical outcomes in compensated cirrhotic patients followed for 6 years . METHODS Four hundred and two patients with compensated HCV-related cirrhosis were prospect ively recruited in a tertiary care academic center . At the time of admission , patients were stratified as compensated ( absence [ stage 1 ] or presence [ stage 2 ] of esophageal varices ) as defined by D'Amico et al. Subjects were followed to identify overall mortality or liver transplantation and clinical complication rates . RESULTS Among 402 subjects , 294 were categorized as stage 1 and 108 as stage 2 . Over a median of 176 weeks , 42 deaths occurred ( 10 % ) , of which 30 were considered liver-related ( 7 % ) and 12 non-liver-related ( 3 % ) ; eight individuals ( 2 % ) underwent liver transplantation ; 30 patients ( 7 % ) developed HCC , 67 individuals in stage 1 ( 22 % ) developed varices and any event of clinical decompensation occurred in 80 patients ( 20 % ) . The 6-year cumulative overall mortality or liver transplantation was 15 % and 45 % , for stages 1 and 2 , respectively ( p<0.001 ) . The cumulative 6-year HCC incidence was significantly higher among patients with varices ( 29 % ) than those without varices ( 9 % ) , p<0.001 . Similarly , the cumulative 6-year incidence of any clinical liver-related complication was higher in patients with stage 2 ( 66 % ) as compared to 26 % in those with stage 1 , respectively ( p<0.001 ) . CONCLUSIONS Our results indicate significant morbidity and mortality and clinical outcome rates in compensated cirrhotic patients with varices ( stage 2 ) PURPOSE Despite the absence of conclusive data , portal vein ( PV ) thrombosis is considered a contraindication to transarterial chemoembolization ( TACE ) in patients with unresectable hepatocellular carcinoma ( HCC ) . The purpose of our study was to establish the safety of TACE in such patients and identify key prognostic factors and survival . MATERIAL S AND METHODS Data were prospect ively collected from 32 consecutive patients with unresectable HCC and PV thrombosis who underwent treatment with TACE . History and physical examination , relevant laboratory values , and contrast material -enhanced magnetic resonance ( MR ) images were obtained before each TACE procedure . Repeated TACE was performed every 6 weeks unless patients developed a contraindication or MR imaging showed complete response . RESULTS Median overall survival was 9.5 months ( range , 3 - 50 months ) . Child-Pugh numerical disease stage was the prognostic factor most strongly related to survival . The 30-day mortality rate was zero and there was no evidence of TACE-related hepatic infa rct ion or acute liver failure . The 6- , 9- , 12- , and 18-month survival rates were 60 % , 47 % , 25 % , and 12.5 % , respectively . CONCLUSIONS PV thrombosis should not be considered a contraindication to TACE . Compared with historical control subjects who received traditional forms of treatment , the patients in the present study had extended survival . However , prospect i ve r and omized trials are necessary to show this conclusively and to show which subgroups benefit Transcatheter arterial chemoembolization ( TACE ) has been contraindicated for the treatment of patients with hepatocellular carcinoma ( HCC ) and main portal vein ( MPV ) obstruction because of the potential risk of hepatic insufficiency result ing from ischemia after TACE . The current controlled study was undertaken to assess the safety , efficacy , and predictive factors of favorable response to TACE in patients with HCC and MPV obstruction with good hepatic function and adequate collateral circulation around the MPV UNLABELLED Treatment with sorafenib of patients with advanced hepatocellular carcinoma is challenged by anticipated discontinuation due to tumor progression , liver decompensation , or adverse effects . While postprogression survival is clearly determined by the pattern of tumor progression , underst and ing the factors that drive prognosis in patients who discontinued sorafenib for any reason may help to improve patient management and second-line trial design . Patients consecutively admitted to three referral centers who were receiving best supportive care following permanent discontinuation of sorafenib for any reason were included . Postsorafenib survival ( PSS ) was calculated from the last day of treatment to death or last visit available . Two hundred and sixty patients were included in this prospect i ve study , aged 67 years , 60 % with hepatitis C , 51 % Child-Pugh A , 83 % performance status ( PS ) ≥1 , 41 % with macroscopic vascular invasion , and 38 % with extrahepatic tumor spread . Overall , median PSS was 4.1 ( 3.3 - 4.9 ) months , result ing from 4.6 ( 3.3 - 5.7 ) months for 123 progressors , 7.3 ( 6.0 - 10.0 ) months in 77 with adverse effects , and 1.8 ( 1.6 - 2.4 ) months in 60 decompensated patients ( P < 0.001 ) . Postsorafenib survival was independently predicted by PS , prothrombin time , extrahepatic tumor spread , macrovascular invasion , and reason for discontinuation . Two hundred patients potentially eligible for second-line therapy had a PSS of 5.3 ( 4.6 - 7.1 ) months , which was dependent on reasons of discontinuation ( P = 0.004 ) , PS ( P < 0.001 ) , macrovascular invasion ( P < 0.001 ) , and extrahepatic metastases ( P < 0.002 ) . CONCLUSION Discontinuation due to adverse effects in the absence of macrovascular invasion , extrahepatic metastases , and deteriorated PS predicts the best PSS in compensated patients , thereby setting the stage for both improved patient counseling and selection for second-line therapy Background For patients with hepatocellular carcinoma ( HCC ) with portal vein tumor thrombosis ( PVTT ) , the survival benefit of transarterial chemoembolization ( TACE ) compared with conservative treatment largely remains controversial . The objective of this study was to determine whether TACE confers a survival benefit to patients with HCC and PVTT , and to uncover prognostic factors . Methods Between July 2007 and July 2009 , a prospect i ve two-arm nonr and omized study was performed on consecutive patients with unresectable HCC with PVTT . In one arm , patients were treated by TACE using an emulsion of lipiodol and anticancer agents ± gelatin sponge embolization . In another arm , patients received conservative treatment . Results A total of 164 patients were recruited for the study ( TACE group , n = 84 ; conservative treatment group , n = 80 ) . Patients in the TACE group received a mean of 1.9 ( range , 1–5 ) TACE sessions . The overall median survival for all patients was 5.2 months , and the 12- and 24-month overall survival rates were 18.3 % and 5.6 % , respectively . The 12- and 24-month overall survival rates for the TACE and conservative groups were 30.9 % , 9.2 % , and 3.8 % , 0 % , respectively . The TACE group had significantly better survivals than the conservative group ( P < 0.001 ) . On subgroup analysis of segmental and major PVTT , the TACE group also had significantly better survivals ( P = 0.002 , P = 0.002 ) . The treatment type , PVTT extent , tumor size , and serum bilirubin were independent prognostic factors of survival on multivariate analysis . Conclusions TACE was safe and feasible in selected HCC patients with PVTT and it had survival benefit over conservative treatment The classifications of hepatocellular carcinoma ( HCC ) currently used are based on prognostic factors obtained from studies performed years ago when most tumors were diagnosed at advanced stages and the survival rates were substantially poor . Recent investigations have review ed the survival of early tumors properly selected to receive radical therapies and the natural outcome of nonsurgical HCC patients . These data enable a new staging system to be proposed , the Barcelona Clinic Liver Cancer ( BCLC ) staging classification , that comprises four stages that select the best c and i date s for the best therapies currently available . Early stage ( A ) includes patients with asymptomatic early tumors suitable for radical therapies -- resection , transplantation or percutaneous treatments . Intermediate stage ( B ) comprises patients with asymptomatic multinodular HCC . Advanced stage ( C ) includes patients with symptomatic tumors and /or an invasive tumoral pattern ( vascular invasion/extrahepatic spread ) . Stage B and C patients may receive palliative treatments/new agents in the setting of phase II investigations or r and omized controlled trials . End-stage disease ( D ) contain patients with extremely grim prognosis ( Okuda stage III or PST 3 - 4 ) that should merely receive symptomatic treatment Purpose To conduct a single-center , open-label , r and omized , controlled trial to compare the effectiveness and safety of ( a ) ginsenoside Rg3 combined with transcatheter arterial chemoembolization ( TACE ) and ( b ) TACE alone in patients with advanced hepatocellular carcinoma ( HCC ) . Material s and Methods This trial was approved by the Fudan University Zhongshan Hospital ethics committee and was registered with the Chinese Clinical Trial Registry ( ChiCTR-TRC-11001643 ) . After informed consent was obtained , 228 patients with advanced HCC ( Barcelona Clinic Liver Cancer stage C ) were r and omly assigned to receive an Rg3 capsule and undergo TACE ( n = 152 ; mean age ± st and ard deviation , 52.4 years ± 11.8 ; 84.2 % men ) or undergo TACE alone ( n = 76 ; mean age , 52.4 years ± 10.4 ; 82.9 % men ) . TACE was performed by using iodized oil with epirubicin and gelatin sponge after oxaliplatin and 5-fluorouracil were infused . The primary end point was overall survival . Secondary end points included time to progression , time to untreatable progression , disease control rate , and safety . Data were compared with the log-rank test , and survival curves were generated with the Kaplan-Meier method . Results Median overall survival was 13.2 months ( 95 % confidence interval [ CI ] : 11.15 , 15.26 ) in the TACE with Rg3 group and 10.1 months ( 95 % CI : 9.14 , 11.06 ) in the control group ( hazard ratio , 0.63 [ 95 % CI : 0.46 , 0.85 ] ; P = .002 ) . Median time to progression ( 4.3 vs 3.2 months , respectively ; P = .151 ) and median time to untreatable progression ( 8.3 vs 7.3 months , respectively ; P = .063 ) were similar in the two groups . Disease control rate was 69.7 % in the TACE with Rg3 group versus 51.3 % in the control group ( P = .012 ) . Constipation and epistaxis were more frequent in the Rg3 with TACE group ( P < .05 ) . Importantly , Rg3 alleviated some TACE-related adverse syndromes and blood anomalies . Conclusion In patients with advanced HCC and adequate liver function , the combination of TACE and ginsenoside Rg3 may prolong overall survival when compared with TACE alone . ( © ) RSNA , 2016 BACKGROUND A r and omized phase III trial of sorafenib vs. placebo in hepatocellular carcinoma ( HCC ) demonstrated that sorafenib significantly prolonged overall survival ( OS ) compared to placebo . RESEARCH DESIGN AND METHODS A Markov model was developed to evaluate the cost-effectiveness of sorafenib vs. best supportive care ( BSC ) in HCC from the perspective of the Canadian provincial Ministry of Health . The model followed survival and time to progression ( TTP ) in monthly cycles based on the extrapolation of patient level trial data . Health effects were expressed as life-years gained ( LYG ) . Re source use included drugs , physician visits , laboratory tests , scans , and hospitalizations . Unit costs were gathered from public sources and were expressed in 2007 Canadian Dollars . Costs and effects were evaluated over a lifetime and discounted at 5 % . Results were presented as mean + /- st and ard deviation . Deterministic and probabilistic sensitivity analyses were conducted . RESULTS LYG was longer for sorafenib ( 1.52 + /- 0.16 vs. 1.03 + /- 0.09 LYG/patient for sorafenib and BSC , respectively ) . The lifetime total costs were $ 47,511 + /- 3 656 for sorafenib and $ 10,376 + /- 1 649 for BSC , result ing in an incremental cost-effectiveness ratio ( ICER ) of $ 75,821/LYG , and deterministic ICER of $ 75,759/LYG . The results were most sensitive to OS , TTP and BSC costs after progression . Sensitivity analyses results showed that the model was robust . CONCLUSIONS The economic evaluation indicates that sorafenib is cost-effective as compared to BSC in HCC . Limitations include multiple data sources , use of expert opinion for re source use , and the lack of utility data BACKGROUND & AIMS Sorafenib is regarded as the st and ard treatment of care in Barcelona Clinic Liver Cancer ( BCLC ) stage C patients . However , the modest overall survival ( OS ) and disease control rate warrants for a better treatment modality . This study aim ed to investigate the feasibility of combined transarterial chemoembolization and radiotherapy ( TACE+RT ) in comparison with sorafenib for advanced hepatocellular carcinoma ( HCC ) . METHODS AND MATERIAL S From 2007 to 2011 , a total of 116 patients with locally advanced HCC were retrospectively enrolled . Sixty-seven patients treated with TACE+RT were compared with 49 patients treated with sorafenib . Propensity score matching generated a matched cohort composed of 27 patients from each group . OS was the primary endpoint for the analysis . RESULTS At baseline , the sorafenib group had a tendency for a tumour size ≥10 cm , presence of lymph node metastasis and main portal vein tumour thrombosis compared to the TACE+RT group . The OS in the TACE+RT group was significantly longer compared to the sorafenib group ( 14.1 months vs. 3.3 months , P < 0.001 ) . In the propensity score-matched cohort , baseline characteristics did not differ between the two groups . The TACE+RT group showed prolonged OS compared to the sorafenib group ( 6.7 months vs. 3.1 months , P < 0.001 ) . Multivariate analysis revealed that TACE+RT was the only independent prognostic factor associated with survival in the propensity score-matched cohort ( HR = 0.172 , P < 0.001 ) . CONCLUSIONS The OS of TACE+RT was longer compared to sorafenib treatment in locally advanced HCC patients without distant metastasis . Further prospect i ve studies are warranted to confirm these findings This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma ( HCC ) . Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospect i ve r and omized controlled trials ( RCT ) were investigated through uni‐ and multivariate analyses . None of them was suitable for radical therapies ( surgical resection , liver transplantation , or ethanol injection ) or presented end‐stage disease as reflected by an Okuda stage 3 or a Performance Status ≥3 . Sixty‐five patients were Child‐Pugh A , 34 were B , and 3 were C. Most of them exhibited a preserved Performance Status Test ( PST ) ( 0 = 56 ; 1 = 38 ; 2 = 8) . Tumor was solitary in 26 ( ≤5 cm in 16 ) and multinodular/massive in 76 . After a median follow‐up of 17 months , 79 patients died , the 1‐ , 2‐ , and 3‐year survival being 54 % , 40 % , and 28 % . The multivariate study identified PST ( P = .01 ) , constitutional syndrome ( P = .04 ) , vascular invasion ( P = .001 ) , and extrahepatic spread ( P = .04 ) as independent predictors for mortality . The 1‐ , 2‐ , and 3‐year survival for the 48 patients without adverse factors ( Stage 0 ) was 80 % , 65 % , and 50 % , respectively , and 29 % , 16 % , and 8 % in the 54 patients with at least one adverse parameter ( Stage I ) . Therefore , Stage 0 would correspond to an intermediate stage , while Stage I would represent an advanced status , before reaching an end‐stage phase . In conclusion , the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern . Therapeutic trials should be design ed and evaluated considering these characteristics A multicenter r and omized controlled trial established sorafenib as a st and ard of care for patients with advanced hepatocellular carcinoma ( HCC ) . Because the study was prematurely interrupted due to survival benefits in the sorafenib arm , we conducted an observational study to adequately assess risks and benefits of this regimen in field practice . Starting in 2008 , all clinical ly compensated patients with advanced HCC and those with an intermediate HCC who were unfit or failed to respond to ablative therapies were consecutively evaluated in six liver centers in Italy , for tolerability as well as radiologic and survival response to 800‐mg/d sorafenib therapy . Treatment was down‐dosed or interrupted according to drug label . Two hundred ninety‐six patients ( 88 % Child‐Pugh A , 75 % Barcelona Clinic Liver Cancer [BCLC]‐C , and 25 % BCLC‐B ) received sorafenib for 3.8 months ( 95 % CI 3.3‐4.4 ) . Two hundred sixty‐nine ( 91 % ) patients experienced at least one adverse event ( AE ) , whereas 161 ( 54 % ) had to reduce dosing . Treatment was interrupted in 103 ( 44 % ) for disease progression , in 95 ( 40 % ) for an AE , and in 38 ( 16 % ) for liver deterioration . The median survival was 10.5 months in the overall cohort , 8.4 months in BCLC‐C versus 20.6 months in BCLC‐B patients ( P < 0.0001 ) , and 21.6 months in the 77 patients treated for > 70 % of the time with a half dose versus 9.6 months in the 219 patients treated for > 70 % of the time with a full dose . At month 2 of treatment , the overall radiologic response was 8 % . Eastern Cooperative Oncology Group performance status , macrovascular invasion , extrahepatic spread of the tumor , radiologic response at month 2 , and sorafenib dosing were independent predictors of shortened survival . Conclusion : Overall , safety , effectiveness , and generalizability of sorafenib therapy in HCC was vali date d in field practice . The effectiveness of half‐dosed sorafenib may have implication s for tailored therapy . ( HEPATOLOGY 2011 BACKGROUND & AIMS The Sorafenib Hepatocellular Carcinoma ( HCC ) Assessment R and omized Protocol ( SHARP ) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC . In this trial , 602 patients with well-preserved liver function ( > 95 % Child-Pugh A ) were r and omized to receive either sorafenib 400 mg or matching placebo orally b.i.d . on a continuous basis . Because HCC is a heterogeneous disease , baseline patient characteristics may affect individual responses to treatment . In a comprehensive series of exploratory subgroup analyses , data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety of sorafenib . METHODS Five subgroup domains were assessed : disease etiology , tumor burden , performance status , tumor stage , and prior therapy . Overall survival ( OS ) , time to progression ( TTP ) , disease control rate ( DCR ) , and safety were assessed for subgroups within each domain . RESULTS Subgroup analyses showed that sorafenib consistently improved median OS compared with placebo , as reflected by hazard ratios ( HRs ) of 0.50 - 0.85 , similar to the complete cohort ( HR=0.69 ) . Sorafenib also consistently improved median TTP ( HR , 0.40 - 0.64 ) , except in HBV-positive patients ( HR , 1.03 ) , and DCR . Results are limited by small patient numbers in some subsets . The most common grade 3/4 adverse events included diarrhea , h and -foot skin reaction , and fatigue ; the incidence of which did not differ appreciably among subgroups . CONCLUSIONS These exploratory subgroup analyses showed that sorafenib consistently improved median OS and DCR compared with placebo in patients with advanced HCC , irrespective of disease etiology , baseline tumor burden , performance status , tumor stage , and prior therapy BACKGROUND The phase III Sorafenib Asia-Pacific ( AP ) trial-conducted in China , Taiwan and South Korea - confirmed that sorafenib improves overall survival ( OS ) and is safe for patients with advanced hepatocellular carcinoma ( HCC ) . We performed a series of exploratory subset analyses to determine whether baseline status affected response to sorafenib . METHODS In the Sorafenib AP trial , 226 patients with well-preserved liver function ( > 95 % Child-Pugh A ) were r and omised 2:1 to sorafenib 400 mg bid or matching placebo . Subanalyses were based on aetiology ( hepatitis B virus present/absent ) ; tumour burden ( macroscopic vascular invasion and /or extrahepatic spread present/absent ) ; presence or absence of either lung or lymph node metastasis at baseline , Eastern Cooperative Oncology Group performance status ( 0 , 1 - 2 ) ; serum concentrations of alanine aminotransferase/aspartate aminotransferase ( normal , mildly elevated , moderately elevated ) , alpha-fetoprotein ( normal/elevated ) and total bilirubin ( normal/elevated ) ; and whether or not there was a history of hepatectomy or transarterial chemoembolisation/embolisation . Subgroup assessment s included OS , time to progression ( TTP ) , disease control rate and safety . FINDINGS Sorafenib consistently improved both median OS and median TTP , compared with placebo ( range of hazard ratios ( HR ) , 0.32 - 0.87 and 0.31 - 0.75 , respectively ) . The most common grade 3/4 adverse events were h and -foot skin reaction , diarrhoea and fatigue , the incidence of which was similar between subgroups . INTERPRETATION The efficacy and safety profiles of sorafenib in the sub population s described were comparable with those in the overall study population . These exploratory analyses suggest that sorafenib is effective for patients from the AP region with advanced HCC , irrespective of baseline status |
12,446 | 24,670,019 | We found considerable risk and mortality for AD requiring reoperation , which largely contributed to the overall postoperative mortality | Anastomotic dehiscence ( AD ) requiring reoperation is the most severe complication following anterior rectal resection .
We performed a systematic review on studies that describe AD requiring reoperation and its subsequent mortality after anterior resection for rectal carcinoma . | Purpose : This study evaluated the risk factors for anastomotic leakage after laparoscopic surgery for rectal cancer using a stapling technique . Methods : The total prospect i ve registry of 111 patients with rectal cancer who initially underwent laparoscopic low anterior resection using a stapling technique was review ed . Univariate and multivariate analyses were carried out to identify relevant risk factors . Results : Overall anastomotic leakage rate was 5.4 % ( 6/111 ) . Univariate analysis demonstrated that body mass index ( BMI ) ( P=0.0377 ) was significantly associated with anastomotic leakage . After univariate analysis , the variables of BMI and the size of the circular stapler ( P=0.0923 ) were selected for multivariate analysis , as their P values were < 0.2 , and multivariate analysis demonstrated that BMI was independently predictive of developing anastomotic leakage ( P=0.0458 ) . Conclusions : Laparoscopic surgery for rectal cancer using a stapling technique can be performed safely without increasing the risk of anastomotic leakage , and increased BMI might be a potential risk factor for anastomotic leakage Objective : To assess with a single-blinded , multicenter , r and omized trial , the postoperative results in patients undergoing sphincter-saving rectal resection for cancer without preoperative mechanical bowel preparation ( MBP ) . Background : The collective evidence from literature strongly suggests that MBP , before elective colonic surgery , is of no benefit in terms of postoperative morbidity . Very few data and no r and omized study are available for rectal surgery and preliminary results conclude toward the safety of rectal resection without MBP . Methods : From October 2007 to January 2009 , patients scheduled for elective rectal cancer sphincter-saving resection were r and omized to receive preoperative MBP ( ie , retro grade enema and oral laxatives ) or not . Primary endpoint was the overall 30-day morbidity rate . Secondary endpoints included mortality rate , anastomotic leakage rate , major morbidity rate ( Dindo III or more ) , degree of discomfort for the patient , and hospital stay . Results : A total of 178 patients ( 103 men ) , including 89 in both groups ( no-MBP and MBP groups ) , were included in the study . The overall and infectious morbidity rates were significantly higher in no-MBP versus MBP group , 44 % versus 27 % , P = 0.018 , and 34 % versus 16 % , P = 0.005 , respectively . Regarding both anastomotic leakage and major morbidity rates , there was no significant difference between no-MBP and MBP group : 19 % versus 10 % ( P = 0.09 ) and 18 % versus 11 % ( P = 0.69 ) , respectively . Moderate or severe discomfort was reported by 40 % of prepared patients . Mortality rate ( 1.1 % vs 3.4 % ) and mean hospital stay ( 16 vs 14 days ) did not differ significantly between both groups . Conclusions : This first r and omized trial demonstrated that rectal cancer surgery without MBP was associated with higher risk of overall and infectious morbidity rates without any significant increase of anastomotic leakage rate . Thus , it suggests continuing to perform MBP before elective rectal resection for cancer . This study is registered with clinical trials.gov , number NCT00554892 PURPOSE : This study was design ed to identify the clinical features of anastomotic leakage after laparoscopic resection of rectal cancer and to evaluate the outcomes of laparoscopic management for this problem . METHODS : Prospect ively collected data were obtained from 307 patients with rectal cancer who underwent laparoscopic proctectomy and primary anastomosis . Age , sex , tumor location , tumor stage , body mass index , comorbidities , ileostomy , conversion , intraoperative blood loss , operative time , previous abdominal operation , and hospital stay were analyzed for patients with or without anastomotic leakage . Management and outcome of anastomotic leakage also were analyzed . RESULTS : Anastomotic leakage occurred in 29 patients ( 9.4 percent ) . Diverting ileostomy was initially fashioned in 65 patients ( 21.2 percent ) . Leakage was related to young age , male sex , lower tumor location , and longer operation time . Ten patients ( 34.5 percent ) were successfully managed with conservative treatment . Seventeen patients ( 58.6 percent ) were managed via a laparoscopic approach . Open surgery was performed in two patients who showed diffuse fecal soiling or had previous conversion , respectively . There was no mortality . CONCLUSIONS : When leakage occurs , laparotomy or colostomy is not needed routinely . For surgical intervention , the abdominal cavity should be explored first by laparoscopic visualization because the majority of patients can be successfully managed with laparoscopy and ileostomy PURPOSE : The aim of this study was to investigate the role of omentoplasty , by means of intact omentum , in preventing anastomotic leakages after rectal resection . METHODS : Between 1992 and 1997 a total of 112 patients ( 64 males ) with a mean age of 64.7 ( range , 39–83 ) years were r and omly assigned to undergo omentoplasty ( Group A ) or not ( Group B ) to reinforce the colorectal anastomosis after anterior resection for rectal cancer . The primary end point was anastomotic leakage ; the secondary end point included morbility and mortality related to omentoplasty . RESULTS : The two groups were comparable in terms of preoperative and intraoperative characteristics . Staple-ring disruption at plain abdominal radiographs was detected in seven instances in Group A and in ten in Group B patients ( P = not significant ) . Two leakages were evident clinical ly in Group A and seven in Group B ( P<0.05 ) . Three leaks were documented radiologically in Group A and eight in Group B ( P = not significant ) . No complications related to omentoplasty were observed in Group A. There were two repeat operations for anastomotic leakage in Group B. At follow-up , one stricture developed in Group A and three in Group B ( P = not significant ) CONCLUSIONS : Despite a similar incidence of staple-ring defects , a strikingly lower rate of clinical ly and radiologically detected leaks developed in patients su bmi tted to omentoplasty . Although not affecting the incidence of anastomotic disruption , omentoplasty seems to contain the severity of anastomotic leakage Purpose The extraperitoneal rectum is anatomically and biologically different from the intraperitoneal rectum , therefore , the surgical outcomes may be different . This study was design ed to assess operative outcomes of laparoscopic resection of extraperitoneal ( ≤7 cm from the anal verge ) vs. intraperitoneal rectal cancer . Methods Prospect i ve data were collected from 312 patients with rectal cancer who underwent laparoscopic resection . Patients were divided into two groups : extraperitoneal ( EP , n = 138 ) vs. intraperitoneal ( IP , n = 174 ) . Mean follow-up was 33 months . Results Patients with pT3/pT4 accounted for 69.6 percent of EP and 74.1 percent of IP . Circumferential margin was positive in 8.7 percent of EP and 0.6 percent of IP ( P = 0.0004 ) . Anastomotic leakage developed in 9.7 percent of EP vs. 4.6 percent of IP ( P = 0.1081 , overall 6.4 percent ) . Local recurrence rate at three years was 7.6 percent in EP and 0.7 percent in IP ( P = 0.0011 , overall 4 percent ) . By multivariate analysis , extraperitoneal location was a risk factor for local recurrence . Conclusions Laparoscopic resection of rectal cancer , regardless of EP or IP , provided acceptable operative outcomes . There was an increasing tendency for positive circumferential margin , leakage , and local recurrence in EP vs. IP . A multicenter , prospect i ve study is ongoing to identify the high-risk group for local recurrence who may really benefit from neoadjuvant therapy in the era of laparoscopy Anastomotic leakage is a major complication of rectal cancer surgery . The aim of this study was to investigate risk factors associated with symptomatic anastomotic leakage after total mesorectal excision ( TME ) Background Anastomotic leakage is the most significant complication after low anterior resection ( LAR ) for rectal carcinoma , and it is the major cause of postoperative mortality and morbidity . The objective of the present study was to investigate whether the use of a transanal tube as an alternative endoluminal diversion technique for rectal carcinoma can reduce the 30-day leakage rate after LAR . Methods From June 2003 to December 2009 , a total of 398 patients were r and omized to a transanal tube or not after LAR . Inclusion criteria for r and omization were biopsy-proven carcinoma of the rectum located ≤15 cm above the anal verge , measured with a rigid rectoscope ; age ≥ 18 years ; informed consent ; ability to underst and the study information ; estimated survival of > 6 months ; anterior resection for the lesion ; final negative air leakage test ; intact anastomotic stapler rings ; and the absence of major intraoperative adverse events . Results Patient demographics , tumor size and location , Duke ’s stage , preoperative co-morbidity , and operative details were comparable between the two groups in general analysis and subgroup analysis ( double-staple technique and h and sewn technique ) . The overall rate of symptomatic leakage was 6.78 % ( 27 of 398 patients ) . Patients r and omized to a transanal tube ( n = 200 ) had leakage in 4.0 % ( 8 of 200 patients ) and those without a tube ( n = 198 ) in 9.6 % ( 19 of 198 patients ) ( p = 0.026 ) . With regard to the double-staple technique subgroup , 3.7 % ( 7 of 188 ) patients with a tube presented with a symptomatic anastomotic leakage , compared with 9.3 % ( 17 of 182 ) of those without a tube ( p = 0.028 ) . Of the patients with anastomotic leakage in the double-staple technique subgroup , the need for urgent abdominal reoperation was 28.6 % ( two of seven patients ) in those r and omized to a transanal tube and 82.4 % ( 14 of 17 ) in those without ( p = 0.021 ) . The 30-day mortality after LAR was nil . In the double-staple technique subgroup , a quicker resumption of gastrointestinal motility manifested by a smaller ratio of patients with flatus > postoperative day ( POD ) 3 ( p = 0.019 ) and a smaller ratio of poor gastrointestinal electromyogram on POD 3 ( p < 0.001 ) was associated with use of a transanal tube . Additionally , patients with a tube appeared to have a lower rectal resting pressure by POD 3 ( 4.0 ± 2.2 vs. 5.0 ± 2.2 kPa ; p < 0.001 ) or POD 5 ( 4.3 ± 2.3 vs. 5.6 ± 2.3 kPa ; p < 0.001 ) , compared to the resting pressures patients without the device , respectively . A shorter length of hospital stay was associated with use of a transanal tube both in the double-staple technique subgroup ( p < 0.001 ) and the h and sewn technique subgroup ( p = 0.011 ) . Multivariate logistic regression analysis revealed that body mass index > 25 kg/m2 and a poor gastrointestinal electromyogram on POD 3 were found to be independent risk factors for anastomotic leakage in the low anastomosis subgroup . Conclusions The presence of a transanal tube is effective and safe in decreasing the rate of clinical ly significant anastomotic leaks and in mitigating the clinical consequences of leakage after anterior resection for rectal cancer with the technique of total mesorectal excision and double-staple anastomosis . The potential benefits of transanal tube placement are multifactorial , including drainage , reduction of endoluminal pressure , and promotion of gastrointestinal motility . Obesity and poor gastrointestinal electromyogram on POD 3 are independent risk factors for anastomotic leakage in patients with low anastomosis BACKGROUND Controversy still exists concerning the impact of patient and tumor characteristics on anastomotic dehiscence after resection for rectal cancer . METHODS Between January 1986 and July 2006 , 472 patients underwent curative rectal resection . Patient and tumor characteristics , details of treatment , and postoperative results were recorded prospect ively . Univariate and multivariate analysis were applied to identify risk factors for anastomotic leakage . RESULTS In our patients , the anastomotic leak rate was 10.4 % ( 49 of 472 patients ) , and mortality was 2.2 % ( 1 of 49 patients ) . In univariate analysis , tumor diameter and absence of a protective stoma were associated with increased anastomotic leak rate , whereas American Society of Anesthesiologists ( ASA ) score and tumor localization showed borderline significance . In multivariate analysis , tumor diameter , tumor localization , and absence of a protective stoma were significantly associated with anastomotic leakage . CONCLUSIONS Patients with large and low lying rectal tumors are at high risk for anastomotic leakage . A protective stoma significantly decreases the rate of clinical leaks and subsequent reoperation after low anterior resection Purpose The anastomotic leakage rate after rectal resection has been reported to be approximately 2.5 - 21 percent , but most results were associated with open surgery . The aim of this study was to identify risk factors and their relationship to the experience of the surgeon for anastomotic leakage after laparoscopic rectal resection . Methods Between March 2003 and December 2008 , 156 patients underwent a laparoscopic rectal resection without a diverting ileostomy . The patients ' characteristics , the details of treatment , the intraoperative results , and the postoperative results were recorded prospect ively . Univariate and multivariate analyses were applied to identify risk factors for anastomotic leakage . Results The majority of operations were performed for malignant disease ( n = 150 ; 96.2 % ) , and 96 patients ( 61.5 % ) were males . Conversion to open surgery occurred in 1 case ( 0.6 % ) . The anastomotic leak rate was 10.3 % ( 16/156 ) , and there were no mortalities . In the univariate analysis , tumor location , anastomotic level , intraoperative events , and operation time were associated with increased anastomotic leakage rate . In the multivariate analysis , anastomotic level ( odds ratio [ OR ] , 6.855 ; 95 % confidence interval [ CI ] , 1.271 to 36.964 ) and operation time ( OR , 8.115 ; 95 % CI , 1.982 to 33.222 ) were significantly associated with anastomotic leakage . Conclusion The important risk factors for anastomotic leakage after laparoscopic rectal resection without a diverting ileostomy were low anastomosis and long operation time . An additional procedure , such as diverting stoma , may reduce the anastomotic leakage if it is selectively applied in cases with these risk factors Background Laparoscopic resection has been shown to be a feasible option in patients with colorectal diseases . However , there have been only a few studies on laparoscopic resection for rectal neoplasm . This report aim ed to evaluate the early outcomes of patients treated by laparoscopic rectal resection for neoplasm . Methods From May 2000 to April 2003 , 100 patients underwent laparoscopic resection for rectal neoplasm with mesorectal excision . Data on the patients ' demographics , operative details , and outcomes were collected prospect ively . In those with successful laparoscopic resection , comparison was made between patients with predominantly intracorporeal surgery ( ICS ) and those with anterior resection performed with extracorporeal rectal transection and anastomosis following intracorporeal bowel mobilization and vessel ligation ( IECS ) . Results Sixty-six men and 34 women ( median age , 69 years ; range , 40–85 ) were included . Operations included 91 anterior resections , eight abdominoperineal resections , and one Hartmann 's procedure . Conversion was required in 15 patients and no conversion was needed in patients treated by laparoscopic abdominoperineal resection . One patient died 30 days after surgery because of liver failure . Postoperative complications occurred in 31 patients . Among them , three had anastomotic leakage and all of them could be treated conservatively . Reoperation was required in one patient with intestinal obstruction . Patients with conversion were found to have significantly more blood loss , longer time to resume diet , a longer hospital stay , and a higher morbidity rate when compared to those with successful laparoscopic surgery . Among those with successful laparoscopic procedures , no difference was observed between patients with ICS ( n = 57 ) and those with IECS ( n = 28 ) , except that a shorter incision and less blood loss were found in patients in the former group . Conclusions Laparoscopic rectal resection with mesorectal dissection is feasible . The operating mortality and reoperation rates were low . Conversion was associated with an increased morbidity rate , leading to a longer hospital stay . Laparoscopically assisted anterior resection with rectal transection by a transverse stapler through the abdominal incision produced similar results when compared to a procedure that was predominantly intracorporeally performed BACKGROUND Laparoscopic rectal transection carries the risk of anastomotic leakage because of its technical difficulty and long staple line with an inadequate cutting angle . Our objective was to investigate the risk factors affecting anastomotic leakage after laparoscopic intracorporeal colorectal anastomosis with a double stapling technique . STUDY DESIGN Between November 2006 and September 2008 , 270 consecutive patients underwent laparoscopic sigmoidectomy and anterior resection with double stapling technique for distal sigmoid and rectal cancer . Data were collected prospect ively . Univariate and multivariate analyses were performed to determine risk factors for anastomotic leakage . Additionally , we evaluated the relationship between the number of stapler firings and clinical parameters . RESULTS Anastomotic leakage was noted in 17 ( 6.3 % ) of 270 patients . In univariate analyses , tumor location ( p = 0.021 ) , operation time ( p = 0.025 ) , number of stapler firings ( p = 0.040 ) , and diameter of the circular stapler ( p = 0.022 ) were significant risk factors for anastomotic leakage . Multivariate analyses showed that middle or lower rectal cancer was an independent factor affecting anastomotic leakage ( p = 0.013 ) . The number of stapler firings increased significantly in men ( p = 0.023 ) , in patients with a tumor at a lower level ( p = 0.034 ) , and in those with longer operation times ( p < 0.001 ) . CONCLUSIONS A reduction in the number of linear stapler firings is necessary to avoid anastomotic leakage after laparoscopic colorectal anastomosis with a double stapling technique . We recommend that a diverting ileostomy is m and atory in patients with middle and lower rectal cancer where multiple linear staplers were used Background This study was design ed to apply modern statistical methods to evaluate risk factors for anastomotic leakage after rectal cancer resection in a retrospective cohort of patients who received a colorectostomy . Whereas a diverting stoma and tumor height are considered proven risk factors for anastomotic leakage , a lack of evidence about additional risk factors persists . Methods In a single-center study , 527 consecutive patients who received a colorectostomy after rectal cancer resection between 1991 and 2008 were retrospectively assessed . In addition to traditional uni- and multivariate regression , locally weighted scatterplot smoothing ( LOWESS ) regression and bootstrap analysis were applied to increase internal validity . Results Anastomotic leakage occurred in 70 patients ( 13.3 % ; 95 % confidence interval ( CI ) , 10.5–16.5 % ) and mortality was 2.5 % ( 95 % CI , 1.4–4.2 % ) . Diverting stoma ( odds ratio ( OR ) , 0.4 ; 95 % CI , 0.17–0.61 ) and tumor height ( OR , 0.88 ; 95 % CI , 0.8–0.94 ) were proven to be protective . Neoadjuvant radiotherapy ( OR , 2.15 ; 95 % CI , 1.58–4.24 ) and intraoperative blood loss ( OR , 1.05 ; 95 % CI , 1.02–1.09 ) had a derogatory effect . Bootstrap analysis identified pre-existing vascular disease ( 95.5 % ) , more advanced UICC stage III or IV tumors ( 95.7 % or 91.5 % , respectively ) , and intraoperative ( 96.1 % ) and postoperative ( 99.4 % ) blood substitution as harmful . Both intraoperative and postoperative blood substitution caused a dose-dependent increase in risk . Conclusions Applying statistical resampling methods identified intraoperative blood loss , blood substitution , vascular disease , and advanced UICC stage as risk factors for anastomotic leakage . Greater distances between the tumor and the anal verge and performance of a diverting stoma were associated with a decreased risk of anastomotic leakage Background The aim of the present study was to investigate the usefulness of the transanal drainage tube for prevention of anastomotic leakage and bleeding after anterior resection for rectal cancer . Methods Between January 2007 and May 2011 a nonr and omized prospect i ve study of patients undergoing anterior resection for rectal cancer was done . The patients were divided into the transanal drainage tube ( TDT ) and non-transanal drainage tube ( NTDT ) groups according to whether the transanal drainage tube was used in the operation . Clinical characteristics and postoperative complications were compared between the TDT and NTDT groups . Results The study included 81 patients in the TDT group and 77 patients in the NTDT group . In the TDT group , anastomotic leakage occurred in 2 patients and no anastomotic bleeding occurred . In the NTDT group , anastomotic leakage occurred in 7 patients and anastomotic bleeding occurred in 2 patients . The TDT group had significantly fewer anastomotic complications compared with the NTDT group ( 2.5 vs 11.7 % ; P = 0.029 ) . Furthermore , the TDT group showed an obvious reduction in the rate of anastomotic leakage and anastomotic bleeding compared with the NTDT group ( 2.5 vs 7.8 % and 0.0 vs 2.6 % ) , but because the number of cases is relatively small , the difference did not reach statistical significance ( P = 0.160 and P = 0.236 ) . Conclusions The use of a transanal drainage tube in anterior resection for rectal cancer may be a simple , safe , and effective means of preventing or reducing the occurrence of anastomotic leakage and bleeding . A larger-scale single or multi-center prospect i ve r and omized study or a meta- analysis including similar studies is necessary for further elucidation of this issue Purpose The role of laparoscopic resection in the management of rectal cancer is still controversial . We prospect ively evaluated patient survival and outcomes in patients undergoing laparoscopic rectal resection for rectal cancer at a single institution . Methods From November 1999 to November 2005 , 107 patients with rectal cancer were treated by laparoscopy . Exclusion criteria were : metastatic disease , advanced disease with invasion of adjacent structures , clinical or radiologic involvement of the external anal sphincter , previous colonic resection , synchronous colonic adenocarcinoma , and contraindications to laparoscopy . All patients were followed prospect ively for survival and complications . Survival was calculated by the Kaplan-Meier method . Results A laparoscopic sphincter-saving procedure was performed in 104 patients , 2 patients had a laparoscopic Miles operation , and 1 underwent a laparoscopic Hartmann ’s procedure . Mean operating time was 278 ( range , 135–430 ) minutes . Conversion to open surgery was required in 20 of 107 patients ( 18.7 percent ) . Overall morbidity was 27 percent , anastomotic leakage occurred in 14 of 104 patients ( 13.5 percent ) . There was no postoperative mortality . A mean of 18 ( range , 1–49 ) lymph nodes was removed . Mean distance of distal margin from tumor was 2.6 ( range , 0.5–10 ) cm ; in two patients there was microscopic invasion of the distal margin . Mean hospital stay was nine ( range , 4–43 ) days . Mean follow-up was 35.8 months . There was local recurrence in 1 of 107 patients ( 0.95 percent ) ; there were no port site metastases . Actuarial five-year and disease-free survival rates are 81.4 and 79.8 percent , respectively . Conclusions Laparoscopic rectal surgery is feasible and oncologically radical but also technically dem and ing ( conversion rate , 18.7 percent ) , time-consuming ( mean operating time , 278 minutes ) , and associated with specific intraoperative complications . At present , the technique should only be performed in specialist centers by teams experienced in laparoscopic surgery Eight r and omized clinical trials and two meta‐analyses recently question ed the value of preoperative mechanical bowel preparation ( MBP ) in colorectal surgery . However , very few patients having rectal surgery were included in these studies . The aim of this study was to assess whether rectal cancer surgery can be performed safely without MBP PURPOSE : This study was undertaken to test the efficacy of an extreme policy of sphincter conservation by combining precise total mesorectal excision with low stapling techniques and endoluminal lavage to guard against implantation . METHODS : A total of 136 consecutive operations for cancer below 5 cm from the anal verge has been prospect ively documented and followed for a mean of 7.7 ( range , 1–18 ) years . A total of 105 of the operations were anterior resections ( 77 percent ) , and 31 were abdominoperineal excisions ( 23 percent ) . RESULTS : The oncologic results in the 105 patients who underwent anterior resections appear greatly superior to those of the patients who underwent abdominoperineal excisions , although the number of abdominoperineal excisions was small ( 31 ) . Actuarial local recurrence at six years for anterior resection and total mesorectal excision was 1 percent for 85 curative procedures and 4 percent for all cases ( n=100 ) , compared with 33 and 47 percent for abdominoperineal excisions ( n=15 and 31 ) . Only four recurrences were observed below the level of the levators , three in the wound of an abdominoperineal excision and one in a stapled anastomosis after a palliative excision . No cases of nodal metastasis in the ischiorectal fossa were observed . CONCLUSION : In a unit specializing in sphincter conservation , precise total mesorectal excision from above appears oncologically superior to abdominoperineal excision . Three-fourths of patients with carcinoma of the lower one-third of the rectum can be offered sphincter-conserving surgery , although temporary defunctioning is probably prudent in such cases . The wound of an abdominoperineal excision may be a prerequisite for perineal recurrence , which may often be caused by implantation OBJECTIVE Surgical technique and peri-operative management of rectal carcinoma have developed substantially in the last decades . Despite this , morbidity and mortality after anterior resection of the rectum are still important problems . The aim of this study was to identify risk factors for anastomotic leakage in anterior resection and to assess the role of a temporary stoma and the need for urgent re-operations in relation to anastomotic leakage . PATIENTS AND METHODS In a nine-year period , from 1987 to 1995 , a total of 6833 patients underwent elective anterior resection of the rectum in Sweden . A r and om sample of 432 of these patients was analysed ( sample size 6.3 % ) . The associations between death and 10 patient- and surgery-related variables were studied by univariate and multivariate analysis . Data were obtained by review of the hospital files from all patients . RESULTS The incidence of symptomatic clinical ly evident anastomotic leakage was 12 % ( 53/432 ) . The 30-day mortality was 2.1 % ( 140/6833 ) . The rate of mortality associated with leakage was 7.5 % . A temporary stoma was initially fashioned in 17 % ( 72/432 ) of the patients , and 15 % ( 11/72 ) with a temporary stoma had a clinical leakage , compared with 12 % ( 42/360 ) without a temporary stoma , not significant . Multivariate analysis showed that low anastomosis ( < or = 6 cm ) , pre-operative radiation , presence of intra-operative adverse events and male gender were independent risk factors for leakage . The risk for permanent stoma after leakage was 25 % . Females with stoma leaked in 3 % compared to men with stoma who leaked in 29 % . The median hospital stay for patients without leakage was 10 days ( range 5 - 61 days ) and for patients with leakage 22 days ( 3 - 110 days ) . CONCLUSION In this population based study , 12 % of the patients had symptomatic anastomotic leakage after anterior resection of the rectum . Postoperative 30-day mortality was 2.1 % . Low anastomosis , pre-operative radiation , presence of intra-operative adverse events and male gender were independent risk factors for symptomatic anastomotic leakage in the multivariate analysis . There was no difference in the use of temporary stoma in patients with or without anastomotic leakage BACKGROUND The aim of this study was to evaluate whether the use of fibrin glue as a sealant over an anastomosis is a risk factor for anastomotic leakage after laparoscopic rectal cancer surgery . METHODS Prospect i ve data were collected from 223 patients with rectal cancer who underwent laparoscopic resection without defunctioning stoma . RESULTS A total of 104 patients underwent laparoscopic rectal resection , followed by the application of fibrin glue over the stapled anastomosis , while 119 underwent surgery alone . No difference in clinical ly significant leakage was observed between the fibrin and the nonfibrin groups ( 5.8 % vs 10.9 % , P = .169 ) . In multivariate analysis , extraperitoneal tumor location and operation duration > 220 minutes were independently associated with anastomotic leakage . CONCLUSIONS Significant predictors of anastomotic leakage include extraperitoneal tumor location and operation length > 220 minutes . Fibrin glue application over the stapled anastomosis was not found to be significantly associated with anastomotic leakage |
12,447 | 26,084,526 | There is evidence for the effectiveness of neuromuscular training strategies in the reduction of injury in numerous team sports . | Youth have very high participation and injury rates in sport .
Sport is the leading cause of injury in youth .
Sport injury reduces future participation in physical activity which adversely affects future health .
Sport injury may lead to overweight/obesity and post-traumatic osteoarthritis .
The objective of the systematic review and meta- analysis was to evaluate the efficacy of injury prevention neuromuscular training strategies in youth sport . | Background A protective effect on injury risk in youth sports through neuromuscular warm-up training routines has consistently been demonstrated . However , there is a paucity of information regarding the quantity and quality of coach-led injury prevention programmes and its impact on the physical performance of players . Objective The aim of this cluster-r and omised controlled trial was to assess whether different delivery methods of an injury prevention programme ( FIFA 11 + ) to coaches could improve player performance , and to examine the effect of player adherence on performance and injury risk . Method During the 2011 football season ( May – August ) , coaches of 31 tiers 1–3 level teams were introduced to the 11 + through either an unsupervised website or a coach-focused workshop with and without additional on-field supervisions . Playing exposure , adherence to the 11 + , and injuries were recorded for female 13-year-old to 18-year-old players . Performance testing included the Star Excursion Balance Test ( SEBT ) , single-leg balance , triple hop and jumping-over-a-bar tests . Results Complete preseason and postseason performance tests were available for 226 players ( 66.5 % ) . Compared to the unsupervised group , single-leg balance ( OR=2.8 ; 95 % CI 1.1 to 4.6 ) and the anterior direction of the SEBT improved significantly in the onfield supervised group of players ( OR=4.7 ; 95 % CI 2.2 to 7.1 ) , while 2-leg jumping performance decreased ( OR=−5.1 ; 95 % CI −9.9 to −0.2 ) . However , significant improvements in 5 of 6 reach distances in the SEBT were found , favouring players who highly adhered to the 11 + . Also , injury risk was lower for those players ( injury rate ratio , IRR=0.28 , 95 % CI 0.10 to 0.79 ) . Conclusions Different delivery methods of the FIFA 11 + to coaches influenced players ’ physical performance minimally . However , high player adherence to the 11 + result ed in significant improvements in functional balance and reduced injury risk Background Little is known about the influence of compliance with neuromuscular training ( NMT ) on the knee injury rate in football . Aim To evaluate team and player compliance with an NMT programme in adolescent female football and to study the association between compliance and acute knee injury rates . Methods Prospect i ve cohort study based on a cluster r and omised controlled trial on players aged 12–17 years with 184 intervention teams ( 2471 players ) and 157 control teams ( 2085 players ) . Exposure and acute time loss knee injuries were recorded . Team and player compliance was recorded by the coaches on a player attendance form . The intervention group was divided into tertiles of compliance . Injury rates were compared by calculating rate ratios ( RRs ) and 95 % CIs using exact Poisson tests with the low-compliance tertile as reference . Seasonal compliance trends were analysed using linear regression . Results Players in the high-compliance tertile had an 88 % reduction in the anterior cruciate ligament ( ACL ) injury rate ( RR 0.12 , 95 % CI 0.01 to 0.85 ) , whereas the rate in the control group players was not significantly different from those in the low-compliance tertile ( RR 0.77 , 95 % CI 0.27 to 2.21 ) . A significant deterioration occurred in team ( b=−3.0 % per month , 95 % CI −5.2 to −0.8 ) and player ( b=−5.0 % per month , 95 % CI −7.1 to −2.9 ) compliance over the season . Conclusions Players with high compliance with the NMT programme had significantly reduced ACL injury rate compared with players with low compliance . Significant deterioration in team and player compliance occurred over the season Objective To evaluate the effectiveness of neuromuscular training in reducing the rate of acute knee injury in adolescent female football players . Design Stratified cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 230 Swedish football clubs ( 121 in the intervention group , 109 in the control group ) were followed for one season ( 2009 , seven months ) . Participants 4564 players aged 12 - 17 years ( 2479 in the intervention group , 2085 in the control group ) completed the study . Intervention 15 minute neuromuscular warm-up programme ( targeting core stability , balance , and proper knee alignment ) to be carried out twice a week throughout the season . Main outcome measures The primary outcome was rate of anterior cruciate ligament injury ; secondary outcomes were rates of severe knee injury ( > 4 weeks ’ absence ) and any acute knee injury . Results Seven players ( 0.28 % ) in the intervention group , and 14 ( 0.67 % ) in the control group had an anterior cruciate ligament injury . By Cox regression analysis according to intention to treat , a 64 % reduction in the rate of anterior cruciate ligament injury was seen in the intervention group ( rate ratio 0.36 , 95 % confidence interval 0.15 to 0.85 ) . The absolute rate difference was −0.07 ( 95 % confidence interval −0.13 to 0.001 ) per 1000 playing hours in favour of the intervention group . No significant rate reductions were seen for secondary outcomes . Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players . However , the absolute rate difference did not reach statistical significance , possibly owing to the small number of events . Trial registration Clinical trials NCT00894595 Background : Sport is the leading cause of injury requiring medical attention among adolescents . We studied the effectiveness of a home-based balance-training program using a wobble board in improving static and dynamic balance and reducing sports-related injuries among healthy adolescents . Methods : In this cluster r and omized controlled trial , we r and omly selected 10 of 15 high schools in Calgary to participate in the fall of 2001 . We then recruited students from physical education classes and r and omly assigned them , by school , to either the intervention ( n = 66 ) or the control ( n = 61 ) group . Students in the intervention group participated in a daily 6-week and then a weekly 6-month home-based balance-training program using a wobble board . Students at the control schools received testing only . The primary outcome measures were timed static and dynamic balance , 20-m shuttle run and vertical jump , which were measured at baseline and biweekly for 6 weeks . Self-reported injury data were collected over the 6-month follow-up period . Results : At 6 weeks , improvements in static and dynamic balance were observed in the intervention group but not in the control group ( difference in static balance 20.7 seconds , 95 % confidence interval [ CI ] 10.8 to 30.6 seconds ; difference in dynamic balance 2.3 seconds , 95 % CI 0.7 to 4.0 seconds ) . There was evidence of a protective effect of balance training in over 6 months ( relative risk of injury 0.2 , 95 % CI 0.05 to 0.88 ) . The number needed to treat to avoid 1 injury over 6 months was 8 ( 95 % CI 4 to 35 ) . Interpretation : Balance training using a wobble board is effective in improving static and dynamic balance and reducing sports-related injuries among healthy adolescents Background Injury prevention programme delivery on adherence and injury risk , specifically involving regular supervisions with coaches and players on programme execution on field , has not been examined . Aim The objective of this cluster-r and omised study was to evaluate different delivery methods of an effective injury prevention programme ( FIFA 11 + ) on adherence and injury risk among female youth football teams . Method During the 4-month 2011 football season , coaches and 13-year-old to 18-year-old players from 31 tier 1–3 level teams were introduced to the 11 + through either an unsupervised website ( ‘ control ’ ) or a coach-focused workshop with ( ‘ comprehensive ’ ) and without ( ‘ regular ’ ) additional supervisions by a physiotherapist . Team and player adherence to the 11 + , playing exposure , history and injuries were recorded . Results Teams in the comprehensive and regular intervention groups demonstrated adherence to the 11 + programme of 85.6 % and 81.3 % completion of total possible sessions , compared to 73.5 % for teams in the control group . These differences were not statistically significant , after adjustment for cluster by team , age , level and injury history . Compared to players with low adherence , players with high adherence to the 11 + had a 57 % lower injury risk ( IRR 0.43 , 95 % CI 0.19 to 1.00 ) . However , adjusting for covariates , this between-group difference was not statistically significant ( IRR=0.44 , 95 % CI 0.18 to 1.06 ) . Conclusion Following a coach workshop , coach-led delivery of the FIFA 11 + was equally successful with or without the additional field involvement of a physiotherapist . Proper education of coaches during an extensive preseason workshop was more effective in terms of team adherence than an unsupervised delivery of the 11 + programme to the team . Trial registration IS RCT N67835569 Young female players in European h and ball have a very high injury incidence , up to 50 injuries per 1000 hours of game . More than half of these injuries happen without any external cause . The aim of the study was to investigate the effect of an intervention programme design ed to reduce the number of injuries in young female players in European h and ball , with special emphasis on injuries in the lower extremities . The programme was created using elite athlete training programmes and those design ed for rehabilitation of injured athletes with functional instability of their ankles and rupture of the anterior cruciate ligament . It included the use of an ankle disk for 10 - 15 min at all practice sessions , for one 10-month season ( August 1995-May 1996 ) . Twenty-two teams participated in the study , and were r and omly assigned to the intervention or control group . Eleven teams with 111 players were r and omised to the intervention group and 11 teams with 126 players to the control group . Data were analysed using a t-test for continuous variables , chi2- analysis and Fisher 's exact test for dichotomous variables and multivariate methods to determine odds-ratios . The results indicated that using the intervention programme decreased the numbers of both traumatic and overuse injuries significantly . The differences in injuries between the groups were 80 % during games and 71 % during practice . In addition , the players in the control group had a 5.9 times higher risk of acquiring an injury than the players in the intervention group OBJECTIVE To study the effects of a school-based injury prevention program on physical activity injury incidence and severity . DESIGN Cluster r and omized controlled trial performed from January 1 , 2006 , through July 31 , 2007 . SETTING Forty Dutch primary schools . PARTICIPANTS A total of 2210 children ( aged 10 - 12 years ) . INTERVENTION Schools were r and omized to receive either the regular curriculum or an intervention program that targeted physical activity injuries . OUTCOME MEASURES Incidence and severity of physical activity injuries per 1000 hours of physical activity participation . RESULTS A total of 100 injuries in the intervention group and 104 injuries in the control group were registered . Nonresponse at baseline or follow-up was minimal ( 8.7 % ) . The Cox regression analyses adjusted for clustering showed a small nonsignificant intervention effect on total ( HR , 0.81 ; 95 % confidence interval [ CI ] , 0.41 - 1.59 ) , sports club ( 0.69 ; 0.28 - 1.68 ) , and leisure time injuries ( 0.75 ; 0.36 - 1.55 ) . However , physical activity appeared to be an effect modifier . In those who were less physically active , the intervention had a larger effect . The intervention reduced the total and leisure time injury incidence ( HR , 0.47 ; 95 % CI , 0.21 - 1.06 ; and 0.43 ; 0.16 - 1.14 ; respectively ) . Sports club injury incidence was significantly reduced ( HR , 0.23 ; 95 % CI , 0.07 - 0.75 ) . CONCLUSION We found a substantial and relevant reduction in physical activity injuries , especially in children in the low active group , because of the intervention . This school-based injury prevention program is promising , but future large-scale research is needed Injuries can be an adverse outcome of participation in sport and recreational activities . The aim of this study was to determine the public health impact of injury during sports and active recreation injury in a select population in Australia . A r and om household telephone survey was conducted quarterly over a 12-month period in a well-defined geographic region , the Latrobe Valley , Australia . Information was collected on participation in sport and active recreation and associated injuries over the previous 2 weeks for all household members aged over 4 years . Injury rates were calculated per 10,000 population and per 1000 sports participants . Data were collected on 1084 persons from 417 households . Overall , 648 people reported participating in at least one sport or active recreation and 34 ( 5.2 % , 95 % CI : 4.8 , 5.6 % ) of these sustained an injury during this activity . Overall , 51.4 % of injured cases had a significant impact : 26.5 % sought treatment , 34.4 % had their activities of daily living adversely affected and 36.0 % had their performance/participation limited . Cricket ( 51 injuries/10,000 population ) , horse riding ( 29/10,000 population ) and basketball ( 25/10,000 population ) had the highest injury rates . After adjusting for participation , cricket ( 242 injuries/1000 participants ) , horse riding ( 122/1000 participants ) and soccer ( 107/1000 participants ) had the highest injury rates . Cricket and soccer were the sports most associated with ' significant ' injuries . Injury prevention efforts should be aim ed at team ball sports ( especially cricket , soccer and netball ) because of their comparatively high rate of both overall and ' significant ' injury To prospect ively evaluate the effect of neuromuscular training on the incidence of knee injury in female athletes , we monitored two groups of female athletes , one trained before sports participation and the other not trained , and a group of untrained male athletes throughout the high school soccer , volleyball , and basketball seasons . Weekly reports included the number of practice and competition exposures and mechanism of injury . There were 14 serious knee injuries in the 1263 athletes tracked through the study . Ten of 463 untrained female athletes sustained serious knee injuries ( 8 noncontact ) , 2 of 366 trained female athletes sustained serious knee injuries ( 0 noncontact ) , and 2 of 434 male athletes sustained serious knee injuries ( 1 noncontact ) . The knee injury incidence per 1000 athlete-exposures was 0.43 in untrained female athletes , 0.12 in trained female athletes , and 0.09 in male athletes ( P 0.02 , chi-square analysis ) . Untrained female athletes had a 3.6 times higher incidence of knee injury than trained female athletes ( P 0.05 ) and 4.8 times higher than male athletes ( P 0.03 ) . The incidence of knee injury in trained female athletes was not significantly different from that in untrained male athletes ( P 0.86 ) . The difference in the incidence of noncontact injuries between the female groups was also significant ( P 0.01 ) . This prospect i ve study demonstrated a decreased incidence of knee injury in female athletes after a specific plyometric training program Objective : To evaluate the effectiveness of a preseason physical training programme that taught l and ing and falling skills in improving l and ing skills technique and preventing injury in junior elite Australian football players . Methods : 723 male players who participated in an under 18 elite competition were studied prospect ively in a non-r and omised controlled trial over two consecutive football seasons . There were 114 players in the intervention group and 609 control players . The eight session intervention programme taught players six l and ing , falling , and recovery skills , which were considered fundamental for safe l and ing in Australian football . L and ing skills taught in these sessions were rated for competence by independent and blinded assessors at baseline and mid-season . Results : Evaluation of l and ing skills found no significant differences between the groups at baseline . Evaluation after the intervention revealed overall improvement in l and ing skills , but significantly greater improvement in the intervention group ( z = −7.92 , p = 0.001 ) . Players in the intervention group were significantly less likely ( relative rate 0.72 , 95 % confidence interval 0.52 to 0.98 ) to sustain an injury during the season than the control group . In particular , the time to sustaining a l and ing injury was significantly less for the intervention group ( relative rate 0.40 , 95 % confidence interval 0.17 to 0.92 ) compared with the control group . Conclusions : L and ing and falling ability can be taught to junior elite Australian football players . Players in the intervention group were protected against injury , particularly injuries related to l and ing and falls Abstract Objective To investigate the effect of a structured warm-up programme design ed to reduce the incidence of knee and ankle injuries in young people participating in sports . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 120 team h and ball clubs from central and eastern Norway ( 61 clubs in the intervention group , 59 in the control group ) followed for one league season ( eight months ) . Participants 1837 players aged 15 - 17 years ; 958 players ( 808 female and 150 male ) in the intervention group ; 879 players ( 778 female and 101 male ) in the control group . Intervention A structured warm-up programme to improve running , cutting , and l and ing technique as well as neuromuscular control , balance , and strength . Main outcome measure The rate of acute injuries to the knee or ankle . Results During the season , 129 acute knee or ankle injuries occurred , 81 injuries in the control group ( 0.9 ( SE 0.09 ) injuries per 1000 player hours ; 0.3 ( SE 0.17 ) in training v 5.3 ( SE 0.06 ) during matches ) and 48 injuries in the intervention group ( 0.5 ( SE 0.11 ) injuries per 1000 player hours ; 0.2 ( SE 0.18 ) in training v 2.5 ( SE 0.06 ) during matches ) . Fewer injured players were in the intervention group than in the control group ( 46 ( 4.8 % ) v ( 76 ( 8.6 % ) ; relative risk intervention group v control group 0.53 , 95 % confidence interval 0.35 to 0.81 ) . Conclusion A structured programme of warm-up exercises can prevent knee and ankle injuries in young people playing sports . Preventive training should therefore be introduced as an integral part of youth sports programmes Background : Risk factors for soccer injuries and possibilities for prevention have been discussed by several authors , but only a few have investigated the effectiveness of preventive interventions . Purpose : The aim of the present study was to evaluate the effects of a prevention program on the incidence of soccer injuries in male youth amateur players . Study Design : Prospect i ve controlled intervention study . Methods : Seven soccer teams took part in a prevention program that focused on education and supervision of coaches and players , while seven other teams were instructed to train and play soccer as usual . Over 1 year all injuries were documented weekly by physicians . Complete weekly injury reports were available for 194 players . Results : The incidence of injury per 1000 hours of training and playing soccer was 6.7 in the intervention group and 8.5 in the control group , which equates to 21 % fewer injuries in the intervention group . The greatest effects were observed for mild injuries , overuse injuries , and injuries incurred during training . The prevention program had greater effects in low-skill than in high-skill teams . Conclusions : The incidence of soccer injuries can be reduced by preventive interventions , especially in low skill level youth teams . Coaches and players need better education regarding injury prevention strategies and should include such interventions as part of their regular training A set of exercises -- the " 11"--have been selected to prevent football injuries . The purpose of this cluster-r and omized controlled trial was to investigate the effect of the " 11 " on injury risk in female youth football . Teams were r and omized to an intervention ( n=59 teams , 1091 players ) or a control group ( n=54 teams , 1001 players ) . The intervention group was taught the " 11 , " exercises for core stability , lower extremity strength , neuromuscular control and agility , to be used as a 15-min warm-up program for football training over an 8-month season . A total of 396 players ( 20 % ) sustained 483 injuries . No difference was observed in the overall injury rate between the intervention ( 3.6 injuries/1000 h , confidence interval ( CI ) 3.2 - 4.1 ) and control group ( 3.7 , CI 3.2 - 4.1 ; RR=1.0 , CI 0.8 - 1.2 ; P=0.94 ) nor in the incidence for any type of injury . During the first 4 months of the season , the training program was used during 60 % of the football training sessions , but only 14 out of 58 intervention teams completed more than 20 prevention training sessions . In conclusion , we observed no effect of the injury prevention program on the injury rate , most likely because the compliance with the program was low Objective : To examine the effectiveness of a sport-specific balance training program in reducing injury in adolescent basketball . Design : Cluster r and omized controlled trial . Setting : Twenty-five high schools in Calgary and surrounding area . Subjects : Nine hundred and twenty high school basketball players ( ages 12 - 18 ) . Intervention : Subjects were r and omly allocated by school to the control ( n = 426 ) and training group ( n = 494 ) . Both groups were taught a st and ardized warm-up program . The training group was also taught an additional warm-up component and a home-based balance training program using a wobble board . Main Outcome Measures : All injuries occurring during basketball that required medical attention and /or caused a player to be removed from that current session and /or miss a subsequent session were then recorded and assessed by a team therapist who was blinded to training group allocation . Results : A basketball-specific balance training program was protective of acute-onset injuries in high school basketball [ RR = 0.71 ( 95 % CI ; 0.5 - 0.99 ) ] . The protective effect found with respect to all injury [ RR = 0.8 ( 95 % CI ; 0.57 - 1.11 ) ] , lower-extremity injury [ RR = 0.83 ( 95 % CI ; 0.57 - 1.19 ) ] , and ankle sprain injury [ RR = 0.71 ( 95 % CI ; 0.45 - 1.13 ) ] were not statistically significant . Self-reported compliance to the intended home-based training program was poor ( 298/494 or 60.3 % ) . Conclusions : A basketball-specific balance training program was effective in reducing acute-onset injuries in high school basketball . There was also a clinical ly relevant trend found with respect to the reduction of all , lower-extremity , and ankle sprain injury . Future research should include further development of neuromuscular prevention strategies in addition to further evaluation of methods to increase compliance to an injury-prevention training program in adolescents OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity OBJECTIVE To determine the effectiveness of coach-led neuromuscular warm-up on reducing lower extremity ( LE ) injuries in female athletes in a mixed-ethnicity , predominantly low-income , urban population . DESIGN Cluster r and omized controlled trial . SETTING Chicago public high schools . PARTICIPANTS Of 258 coaches invited to participate , 95 ( 36.8 % ) enrolled ( 1558 athletes ) . Ninety coaches and 1492 athletes completed the study . INTERVENTIONS We r and omized schools to intervention and control groups . We trained intervention coaches to implement a 20-minute neuromuscular warm-up . Control coaches used their usual warm-up . MAIN OUTCOME MEASURES Coach compliance was tracked by self-report and direct observation . Coaches reported weekly athlete exposures ( AEs ) and LE injuries causing a missed practice or game . Research assistants interviewed injured athletes . Injury rates were compared between the control and intervention groups using χ(2 ) and Fisher exact tests . Significance was set at P < .05 . Poisson regression analysis adjusted for clustering and covariates in an athlete subset reporting personal information ( n = 855 ; 57.3 % ) . RESULTS There were 28 023 intervention AEs and 22 925 control AEs . Intervention coaches used prescribed warm-up in 1425 of 1773 practice s ( 80.4 % ) . Intervention athletes had lower rates per 1000 AEs of gradual-onset LE injuries ( 0.43 vs 1.22 , P < .01 ) , acute-onset noncontact LE injuries ( 0.71 vs 1.61 , P < .01 ) , noncontact ankle sprains ( 0.25 vs 0.74 , P = .01 ) , and LE injuries treated surgically ( 0 vs 0.17 , P = .04 ) . Regression analysis showed significant incidence rate ratios for acute-onset noncontact LE injuries ( 0.33 ; 95 % CI , 0.17 - 0.61 ) , noncontact ankle sprains ( 0.38 ; 95 % CI , 0.15 - 0.98 ) , noncontact knee sprains ( 0.30 ; 95 % CI , 0.10 - 0.86 ) , and noncontact anterior cruciate ligament injuries ( 0.20 ; 95 % CI , 0.04 - 0.95 ) . CONCLUSION Coach-led neuromuscular warm-up reduces noncontact LE injuries in female high school soccer and basketball athletes from a mixed-ethnicity , predominantly low-income , urban population . TRIAL REGISTRATION CLINICAL TRIALS.ORG IDENTIFIER : NCT01092286 Background Ankle sprains are the most common musculoskeletal injuries that occur in athletes , and they have a profound impact on health care costs and re sources . Hypothesis A balance training program can reduce the risk of ankle sprains in high school athletes . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Seven hundred and sixty-five high school soccer and basketball players ( 523 girls and 242 boys ) were r and omly assigned to either an intervention group ( 27 teams , 373 subjects ) that participated in a balance training program or to a control group ( 28 teams , 392 subjects ) that performed only st and ard conditioning exercises . On-site athletic trainers recorded athlete exposures and sprains . Results The rate of ankle sprains was significantly lower for subjects in the intervention group ( 6.1 % , 1.13 of 1000 exposures vs 9.9 % , 1.87 of 1000 exposures ; P = .04 ) . Athletes with a history of an ankle sprain had a 2-fold increased risk of sustaining a sprain ( risk ratio , 2.14 ) , whereas athletes who performed the intervention program decreased their risk of a sprain by one half ( risk ratio , 0.56 ) . The ankle sprain rate for athletes without previous sprains was 4.3 % in the intervention group and 7.7 % in the control group , but this difference was not significant ( P = .059 ) . Conclusion A balance training program will significantly reduce the risk of ankle sprains in high school soccer and basketball players OBJECTIVES To examine rates of sport participation , sport injury , risk factors and sport safety practice s in young adolescents . DESIGN Cross-sectional . SETTING Calgary and area junior high schools . PARTICIPANTS A r and om sample of 1466 students ( aged 12 to 15 years ) . OUTCOME MEASURES Sport injury within one year prior to completing the survey . RESULTS Ninety-three per cent of students participated in sports in the previous year . The injury rate was 60.85 injuries/100 students/year ( 95 % CI 58.29 to 63.35 ) for students reporting at least one sport injury , 29.4 injuries/100 students/year ( 95 % CI 27.08 to 31.81 ) for medically treated injuries , and 12.28 injuries/100 students/year ( 95 % CI 10.64 to 14.07 ) for injuries presenting to a hospital emergency department . The greatest proportion of injuries occurred in basketball ( 14 % ) , soccer ( 12 % ) , hockey ( 8.6 % ) and snowboarding/skiing ( 7.1 % ) . CONCLUSIONS The rates of participation and injury in sports are high in junior high school students . Future research should focus on prevention strategies in sports with high participation and injury rates to have the greatest population health impact BACKGROUND Studies have suggested that exercise programs can reduce the incidence of noncontact injuries of the anterior cruciate ligament in female athletes . We conducted a two-year prospect i ve study to assess the effects of a knee ligament injury prevention exercise program on the incidence of noncontact anterior cruciate ligament injuries in high-school female athletes . METHODS A prospect i ve cohort design was used to study high-school female athletes ( playing soccer , basketball , and volleyball ) from fifteen schools ( 112 teams ) for two consecutive seasons . The schools were divided into treatment and control groups . The treatment group participated in a plyometric-based exercise program twice a week throughout the season . Practice and game exposures and compliance with the exercise program were recorded on a weekly basis . Suspected noncontact anterior cruciate ligament injuries were confirmed on the basis of the history as well as at the time of surgery and /or with magnetic resonance imaging . RESULTS A total of 1439 athletes ( 862 in the control group and 577 in the treatment group ) were monitored . There were six confirmed noncontact anterior cruciate ligament injuries : three in the treatment group , and three in the control group . The incidence of noncontact anterior cruciate ligament injuries per 1000 exposures was 0.167 in the treatment group and 0.078 in the control group , yielding an odds ratio of 2.05 , which was not significant ( p > 0.05 ) . CONCLUSIONS Our results suggest that a twenty-minute plyometric-based exercise program that focuses on the mechanics of l and ing from a jump and deceleration when running performed twice a week throughout the season will not reduce the rate of noncontact anterior cruciate ligament injuries in high-school female athletes Background Among female athletes it has not been established whether a neuromuscular and proprioceptive sports-specific training program will consistently reduce the incidence of anterior cruciate ligament injuries . Purpose To determine whether a neuromuscular and proprioceptive performance program was effective in decreasing the incidence of anterior cruciate ligament injury within a select population of competitive female youth soccer players . Study Design Cohort study ; Level of evidence , 2 . Methods In 2000 , 1041 female subjects from 52 teams received a sports-specific training intervention in a prospect i ve non-r and omized trial . The control group consisted of the remaining 1905 female soccer players from 95 teams participating in the same league who were age and skill matched . In the 2001 season , 844 female athletes from 45 teams were enrolled in the study , with 1913 female athletes ( from 112 teams ) serving as the age- and skill-matched controls . All subjects were female soccer players between the ages of 14 and 18 and participated in either their traditional warm-up or a sports-specific training intervention before athletic activity over a 2-year period . The intervention consisted of education , stretching , strengthening , plyometrics , and sports-specific agility drills design ed to replace the traditional warm-up . Results During the 2000 season , there was an 88 % decrease in anterior cruciate ligament injury in the enrolled subjects compared to the control group . In year 2 , during the 2001 season , there was a 74 % reduction in anterior cruciate ligament tears in the intervention group compared to the age- and skill-matched controls . Conclusion Using a neuromuscular training program may have a direct benefit in decreasing the number of anterior cruciate ligament injuries in female soccer players INTRODUCTION The prevention of injuries in all sports calls for a structured plan . The plan consists , as earlier described , of four steps . We have previously presented studies incorporating all four steps . The studies have shown that it is possible to prevent most injuries in young female players in European h and ball by applying a training programme combining the use of an ankle disc with functional strength training . In the previous studies we were not able to discriminate whether the preventive effect was due to the functional strength training or the training with the ankle disc . The aim of this study was to compare a programme with ankle disc and functional strength training with a programme with functional strength training only . METHODS Twenty h and ball teams were asked to participate , and 16 of 20 h and ball teams agreed to participate . The teams were cluster r and omised to either the programme with or without an ankle disc . RESULTS The group using the programme without the ankle disc had a significantly higher number of traumatic injuries ( 16 vs. 6 ) . The incidences of traumatic injuries in the ankle disc group were 2.4 ( 95 % CI 0.7 ; 6.2 ) injuries per 1000 h of match and 0.2 ( 95 % CI 0.02 ; 0.7 ) injuries per 1000 h of practice . In the group without ankle disc the incidences were 6.9 ( 95 % CI 3.3 ; 12.7 ) injuries per 1000 h of match and 0.6 ( 95 % CI 0.2 ; 1.3 ) injuries per 1000 h of practice . A significantly higher multivariate odds ratio ( 4.8 ) was found in the group not using the ankle disc . In addition the group using the ankle disc had significantly fewer moderate and major injuries . CONCLUSION By adding ankle disc training to a training programme with functional strength training , it is possible to reduce the number of injuries significantly , especially the number of moderate and major injuries Background Soccer is a leading sport for participation and injury in youth . Objective To examine the effectiveness of a neuromuscular prevention strategy in reducing injury in youth soccer players . Design Cluster-r and omised controlled trial . Setting Calgary soccer clubs ( male or female , U13–U18 , tier 1–2 , indoor soccer ) . Participants Eighty-two soccer teams were approached for recruitment . Players from 60 teams completed the study ( 32 training ( n=380 ) , 28 control ( n=364 ) ) . Intervention The training programme was a soccer-specific neuromuscular training programme including dynamic stretching , eccentric strength , agility , jumping and balance ( including a home-based balance training programme using a wobble board ) . The control programme was a st and ardised warm-up ( static and dynamic stretching and aerobic components ) and a home-based stretching programme . Main outcome measures Previously vali date d injury surveillance included injury assessment by a study therapist . The injury definition was soccer injury result ing in medical attention and /or removal from a session and /or time loss . Results The injury rate in the training group was 2.08 injuries/1000 player-hours , and in the control group 3.35 injuries/1000 player-hours . Based on Poisson regression analysis , adjusted for clustering by team and covariates , the incidence rate ratios ( IRR ) for all injuries and acute onset injury were 0.62 ( 95 % CI 0.39 to 0.99 ) and 0.57 ( 95 % CI 0.35 to 0.91 ) . Point estimates also suggest protection of lower extremity , ankle and knee sprain injuries ( IRR=0.68 ( 95 % CI 0.42 to 1.11 ) , IRR=0.5 ( 95 % CI 0.24 to 1.04 ) and IRR=0.38 ( 95 % CI 0.08 to 1.75 ) ) . Conclusions A neuromuscular training programme is protective of all injuries and acute onset injury in youth soccer players |
12,448 | 16,848,905 | Conclusion It appears that the changes in pain scores in subjects with chronic neck pain not due to whiplash who are enrolled in no-treatment and placebo control groups were similarly small and not significantly different .
As well , they do not appear to increase over longer-term follow-up | Background Chronic neck pain is highly prevalent in Western societies , with about 15 % of females and 10 % of males suffering with it at any time .
The course of untreated chronic neck pain patients in clinical trials has not been well-defined and the placebo effect has not been clarified . | To evaluate the efficacy of Chinese medicine ( CM ) acupuncture for chronic neck pain ( CNP ) , a single blind , controlled , crossover , clinical trial was undertaken . Twenty-nine volunteers with CNP were r and omly recruited into two groups . Both groups received two phases of treatment with a washout period between the two phases . Group A ( 14 volunteers ) received CM acupuncture in the first phase and sham acupuncture in the second , while Group B ( 15 volunteers ) received sham in the first and real in the second . CM acupuncture was individualized and consisted of nine sessions on both local and distal points . Manual twisting of the needle was applied on all points plus strong electrical stimulation of distal points in CM acupuncture . Sham acupoints ( lateral to the real ) and sham ( weak ) electrical stimulation was used in the control group . Comparison of subjective and objective measures between the two groups was made at different periods , including baseline , after each phase of treatment , after washout , and after the 16th week follow-up . The subjective measures included pain intensity , duration per day , analgesic medication count , visual analogue scales ( VAS ) and neck disability index ( NDI ) . The objective measures consisted of neck range of motion ( ROM ) and pain threshold ( PT ) . Both the real and sham treatments significantly reduced subjective pain , without significant differences between groups for most subjective measures . Objective measures showed no significant change for either group before and after each period or by inter-groups analysis . A minimum 16-week effect of both real and sham acupuncture was found for subjective measures in the follow-up periods . Further study is recommended with an increased sample size , a longer washout period , and a longer baseline period In the majority of patients with neck pain , symptoms will resolve spontaneously or quite quickly in response to therapy . However , some patients ' symptoms persist for a long period , irrespective of therapy . In this study , 20 patients with persistent ( greater than 8 weeks ) neck pain were enrolled in a double blind , placebo-controlled trial of low energy , pulsed electromagnetic therapy (PEMT)--a treatment previously shown to be effective in soft tissue injuries . For the first 3-week period , group A ( 10 patients ) received active PEMT units while group B ( 10 patients ) received facsimile placebo units . After 3 weeks , both pain ( visual analogue scale ( P less than .023 ) and range of movement ( P less than .002 ) had improved in the group on active treatment compared to the controls . After the second 3 weeks , during which both groups used active units , there were significant improvements in observed scores for pain and range of movement in both groups . PEMT , in the form described , can be used at home easily in the treatment of patients with neck pain . It is frequently successful and without side effects We present a double-blind trial in which a pulsed infrared beam was compared with a placebo in the treatment of myofascial pain in the cervical region . The patients were su bmi tted to 12 sessions on alternate days to a total energy dose of 5 J each . At each session , the four most painful muscular trigger points and five bilateral homometameric acupuncture points were irradiated . Those in the placebo group su bmi tted to the same number of sessions following an identical procedure , the only difference being that the laser apparatus was nonoperational . Pain was monitored using the Italian version of the McGill pain question naire and the Scott-Huskisson visual analogue scale . The results show a pain attenuation in the treated group and a statistically significant difference between the two groups of patients , both at the end of therapy and at the 3-month follow-up examination OBJECTIVE This article examines the specific and nonspecific effects of Japanese acupuncture on chronic myofascial neck pain in a r and omized single-blind trial . DESIGN Forty-six patients were r and omly assigned to receive relevant acupuncture , irrelevant acupuncture , or no-acupuncture control treatment consisting of nonsteroidal anti-inflammatory medication . The two acupuncture groups underwent comparable light shallow needling . The irrelevant acupuncture group received acupuncture at specific sites not relevant for cervical pain . OUTCOME MEASURES The study measures included the McGill Pain Question naire-Short Form ( SF-MPQ ) , the Short-Form Health Survey ( SF-36 ) , the Symptom Checklist 90-Revised ( SCL-90-R ) , medication diary , and physiologic measures . The factors examined as predictors of outcome pain ratings were experience with , beliefs about , and knowledge of acupuncture before treatment ; perceived efficacy , credibility , and logic of acupuncture ; perceived competence of the acupuncturist ; and painfulness of acupuncture . RESULTS No differences were found among the three groups at baseline , except that the relevant acupuncture group reported having had more previous acupuncture treatments . No significant differences in terms of perceived credibility or perceived effectiveness of treatment were found between the two acupuncture groups . The relevant acupuncture group had significantly greater pre-/posttreatment differences in pain than the irrelevant acupuncture and control groups ( p < .05 ) . The nonspecific effects of confidence in the acupuncturist , willingness to try any treatment , mood , and physiologic effect of needling were not predictive of treatment outcome , whereas confidence in the treatment and past experiences with acupuncture did correlate significantly with a decrease in pain . CONCLUSIONS Relevant acupuncture with heat contributes to modest pain reduction in persons with myofascial neck pain . Previous experience with and confidence in treatment help to predict benefit . Measurement of nonspecific effects of alternative therapy is recommended in future clinical trials Thirteen patients with neck pain of at least two years ' duration participated in the study . Patients were r and omly assigned to either an acupuncture group or a placebo TNS ( transcutaneous nerve stimulation ) group . Initial pain scores revealed no significant difference between the groups with respect to pain severity . Patients were treated twice weekly for four weeks , at the end of which pain relief was measured using a simple descriptive scale . Even though an attempt was made to maximize the effect of placebo TNS using strong verbal suggestion , acupuncture still proved superior to placebo in the relief of cervical pain ( p less than 0.01 ) . The implication s of these findings are discussed A r and om sample including 2342 cases representative of all occupational back injuries in Quebec ( 1981 ) was followed up prospect ively over three years to assess the recurrence rate of back problems ( lumbar , thoracic , and cervical ) . Each medical and accident report was review ed to obtain the site of symptoms and occupation . Age , sex , industrial sector , and number of episodes of absence from work were abstract ed from the computerised Quebec Compensation Board files . The recurrence rate was 20.0 % at one year follow up and 36.3 % at three years . A multivariate analysis using a Poisson regression , was performed to model the risk of recurrence over time . Men had a higher chance of recurrence ( risk ratio = 1.85 , 95 % CI = 1.50 - 2.27 ) but among recurrent cases , the average total number of episodes was comparable between men and women . Age showed a protective effect on the probability of recurrence ( 10 years : RR = 0.93 , 95 % CI = 0.88 - 0.98 ) due to the lower recurrence rate in the 45 - 64 year old group ( 31.8 % ) . Cervical and lumbar symptoms had identical recurrence profiles whereas thoracic symptoms had a significantly lower recurrence rate . Drivers had the highest recurrence rate ( 42.1 % ) and nurses had the highest average number of recurrences ( 2.03 ) among recurrent cases . Both occupations had statistically significant excesses after controlling for the other variables Abstract Objectives : To compare the efficacy of acupuncture and conventional massage for the treatment of chronic neck pain . Design : Prospect i ve , r and omised , placebo controlled trial . Setting : Three outpatient departments in Germany . Participants : 177 patients aged 18–85 years with chronic neck pain . Interventions : Patients were r and omly allocated to five treatments over three weeks with acupuncture ( 56 ) , massage ( 60 ) , or “ sham ” laser acupuncture ( 61 ) . Main outcome measures : Primary outcome measure : maximum pain related to motion ( visual analogue scale ) irrespective of direction of movement one week after treatment . Secondary outcome measures : range of motion ( 3D ultrasound real time motion analyser ) , pain related to movement in six directions ( visual analogue scale ) , pressure pain threshold ( pressure algometer ) , changes of spontaneous pain , motion related pain , global complaints ( seven point scale ) , and quality of life ( SF-36 ) . Assessment s were performed before , during , and one week and three months after treatment . Patients ' beliefs in treatment were assessed . Results : One week after five treatments the acupuncture group showed a significantly greater improvement in motion related pain compared with massage ( difference 24.22 ( 95 % confidence interval 16.5 to 31.9 ) , P=0.0052 ) but not compared with sham laser ( 17.28 ( 10.0 to 24.6 ) , P=0.327 ) . Differences between acupuncture and massage or sham laser were greater in the subgroup who had had pain for longer than five years ( n=75 ) and in patients with myofascial pain syndrome ( n=129 ) . The acupuncture group had the best results in most secondary outcome measures . There were no differences in patients ' beliefs in treatment . Conclusions : Acupuncture is an effective short term treatment for patients with chronic neck pain , but there is only limited evidence for long term effects after five treatments . What is already known on this topic Acupuncture is a widespread complementary treatment Evidence from trials have given conflicting results on its use in the treatment of neck pain because of method ological shortcomings and because effects were compared either with alternative treatments or with different sham procedures imitating acupuncture , but not both What this study adds Compared with sham laser acupuncture and massage , needle acupuncture has beneficial effects on mobility and pain related to motion in patients with chronic neck pain Acupuncture was clearly more effective than massage , but differences were not always significant compared with sham laser acupuncture Acupuncture was the best treatment for patients with the myofascial syndrome and those who had had pain for longer than five Abstract Objective To determine the effectiveness of dynamic muscle training and relaxation training for chronic neck pain . Design R and omised controlled trial . Setting Five occupational healthcare centres , Tampere , Finl and . Participants 393 female office workers ( mean age 45 years ) with chronic non-specific neck pain r and omly assigned to 12 weeks of dynamic muscle training ( n = 135 ) or relaxation training ( n = 128 ) , plus one week of reinforcement training six months after baseline ; or ordinary activity ( control group ; n = 130 ) . Main outcome measure Change in intensity of neck pain at three , six , and 12 months . Results No significant difference was found in neck pain between the groups at follow up . However , the range of motion for cervical rotation and lateral flexion increased more in the training groups than in the control group . Conclusions Dynamic muscle training and relaxation training do not lead to better improvements in neck pain compared with ordinary activity The two northernmost counties in Sweden form together 1 of the 39 collaborating centers in the World Health Organization ( WHO ) MONICA ( MONItoring of trends and determinants in CArdiovascular disease ) project . At the last survey in 1999 , we added some questions about cervical spine complaints . Persons r and omly selected from the population in a geographically well-defined area completed a self-administered question naire . The sample included 8,356 subjects and 6,000 ( 72 % ) of them answered . 43 % of the population reported neck pain , more women ( 48 % ) than men ( 38 % ) . Women of working age had more neck pain than older ones , a phenomenon not seen among men . Chronic neck pain , defined as continuous pain of more than 6 months ' duration , was commoner in women ( 22 % ) than men ( 16 % ) . More than one fourth of the cases with chronic symptoms had a history of neck or head trauma and one third of these had sustained a whiplash type of injury . Thus , all types of neck trauma seem to be associated with chronic neck pain Study Design . A r and omized controlled trial with single-blind outcome assessment s. Objective . To evaluate the efficacy of a neck exercise program in patients with chronic neck pain . Summary of Background Data . The effect of exercise for patients with chronic neck pain has been investigated in a number of studies . The efficacy is , however , question able . Methods . A total of 145 patients were r and omly allocated into an exercise ( n = 67 ) and a nonexercise ( control ) group ( n = 78 ) . Patients in the control group were given infrared irradiation and neck care advice . In addition to infrared irradiation and advice , patients in the exercise group had undergone an exercise program with activation of the deep neck muscles and dynamic strengthening of the neck muscles for 6 weeks . Subjective pain and disability and isometric neck muscle strength were measured at baseline , 6 weeks , and 6 months . Analysis was by intention-to-treat . Results . At week 6 , the exercise group had a significantly better improvement in disability score ( P = 0.03 ) , subjective report of pain ( P = 0.01 ) , and in isometric neck muscle strength ( P = 0.57–0.00 ) in most of the directions than the control group . However , significant differences between the two groups were found only in the subjective report of pain and patient satisfaction at the 6-month follow-up . Conclusions . At week 6 , patients with chronic neck pain can benefit from the neck exercise program with significant improvement in disability , pain , and isometric neck muscle strength in different directions . However , the effect of exercise was less favorable at 6 months & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies BACKGROUND AND OBJECTIVES A prospect i ve , double-blind , r and omized , and controlled trial was conducted in patients with chronic myofascial pain syndrome ( MPS ) in the neck to evaluate the effects of infrared low level 904 nm Gallium-Arsenide ( Ga-As ) laser therapy ( LLLT ) on clinical and quality of life ( QoL ) . STUDY DESIGN / PATIENTS AND METHODS The study group consisted of 60 MPS patients . Patients were r and omly assigned to two treatment groups : Group I ( actual laser ; 30 patients ) and Group II ( placebo laser ; 30 patients ) . LLLT continued daily for 2 weeks except weekends . Follow-up measures were evaluated at baseline , 2 , 3 , and 12 weeks . All patients were evaluated with respect to pain at rest , pain at movement , number of trigger points ( TP ) , the Neck Pain and Disability Visual Analog Scale ( NPAD ) , Beck depression Inventory ( BDI ) , and the Nottingham Health Profile ( NHP ) . RESULTS In active laser group , statistically significant improvements were detected in all outcome measures compared with baseline ( P < 0.01 ) while in the placebo laser group , significant improvements were detected in only pain score at rest at the 1 week later of the end of treatment . The score for self-assessed improvement of pain was significantly different between the active and placebo laser groups ( 63 vs. 19 % ) ( P < 0.01 ) . CONCLUSION This study revealed that short-period application of LLLT is effective in pain relief and in the improvement of functional ability and QoL in patients with MPS In this prospect i ve , r and omized , double-blinded , controlled study , we tested the hypothesis that auricular electroacupuncture relieves pain more effectively than conventional manual auricular acupuncture . We studied 21 chronic cervical pain patients without radicular symptoms with insufficient pain relief ( visual analogue scale > 5 ) treated with st and ardized analgesic therapy . All patients received disposable acupuncture needles on the dominant side on the following acupuncture points : cervical spine , shen men , and cushion . In 10 patients , needles were continuously stimulated ( 2-mA constant current , 1 Hz monophasic ) by using the electrical point stimulation device P-STIM ™ . In 11 control patients , no electrical stimulation was administered . All needles were withdrawn 48 h after insertion . Acupuncture was performed once a week for 6 wk . Patients had to complete a question naire assessing pain intensity , psychological well-being , activity , sleep , and dem and for rescue medication ( lornoxicam and tramadol ) . The reduction in pain scores was significant in the electrical acupuncture group . Similarly , psychological well-being , activity , and sleep were significantly improved in patients receiving electrical acupuncture , and consumption of rescue medication was significantly less . These results demonstrate that continuous electrical stimulation of auricular acupuncture points by using the new point stimulation device P-STIM ™ improves the treatment of chronic cervical pain in an outpatient population Study Design . Population ‐based , cross‐sectional mailed survey . Objective . To determine the lifetime , period , and point prevalence of neck pain and its related disability among Saskatchewan adults and investigate the presence and strength of nonresponse bias . Summary of Background Data . In Europe , the life‐time and point prevalence of neck pain is almost as high as the prevalence of low back pain . Similarly , chronic neck pain is highly prevalent and a common source of disability in the working‐age population . However , no studies specifically have documented the prevalence of neck pain and its related disability in North America . Methods . The Saskatchewan Health and Back Pain Survey was mailed to 2184 r and omly selected Saskatchewan adults aged 20‐69 years . Fifty‐five percent of the study population participated . The presence of nonresponse bias was investigated through logistic regression and wave analysis . The Chronic Pain Question naire was used to classify the severity of chronic neck pain . Results . The age‐st and ardized lifetime prevalence of neck pain is 66.7 % ( 95 % confidence interval , 63.8‐69.5 ) , and the point prevalence is 22.2 % ( 95 % confidence interval , 19.7‐24.7 ) . The age‐st and ardized 6‐month prevalence of low‐intensity and low‐disability neck pain is 39.7 % ( 95 % confidence interval , 36.7‐42.7 ) , whereas it is 10.1 % ( 95 % confidence interval , 8.2‐11.9 ) for high‐intensity and low‐disability neck pain and 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) for significantly disabling neck pain . The prevalence of low‐intensity and low‐disability neck pain decreases with age . More women experience high‐disability neck pain than men . Wave analysis suggests that the point prevalence and 6‐month prevalence of high‐intensity and low‐disability neck pain are overestimated in this survey . Conclusion . This cross‐sectional study shows that neck pain is highly prevalent in Saskatchewan and that it significantly disables 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) of the adult population & NA ; The study was carried out to examine whether acupuncture treatment can reduce chronic pain in the neck and shoulders and related headache , and also to examine whether possible effects are long‐lasting . Therefore , 24 female office workers ( 47±9 years old , mean±SD ) who had had neck and shoulder pain for 12±9 years were r and omly assigned to a test group ( TG ) or a control group ( CG ) . Acupuncture was applied 10 times during 3–4 weeks either at presumed anti‐pain acupoints ( TG ) or at placebo‐points ( CG ) . A physician measured the pain threshold ( PPT ) in the neck and shoulder regions with algometry before the first treatment , and after the last one and six months after the treatments . Question naires on muscle pain and headache were answered at the same occasions and again 3 years after the last treatment . The intensity and frequency of pain fell more for TG than for CG ( Pb≤0.04 ) during the treatment period . Three years after the treatments TG still reported less pain than before the treatments ( Pw<0.001 ) , contrary to what CG did ( Pb<0.04 ) . The degree of headache fell during the treatment period for both groups , but more for TG than for CG ( Pb=0.02 ) . Three years after the treatments the effect still lasted for TG ( Pw<0.001 ) while the degree of headache for CG was back to the pre‐treatment level ( Pb<0.001 ) . PPT of some muscles rose during the treatments for TG and remained higher 6 months after the treatments ( Pw<0.05 ) , which contrasts the situation for CG . Adequate acupuncture treatment may reduce chronic pain in the neck and shoulders and related headache . The effect lasted for 3 years The purpose of this double-blind study was to ascertain the effects of helium-neon ( He-Ne ) laser irradiation on skin resistance and pain in patients with trigger points in the neck or low back . This study entailed a partial replication of a previous study by Snyder-Mackler and associates that determined the use of the He-Ne laser increased skin resistance overlying a trigger point . Twenty-four patients were r and omly assigned to either a treatment or a control group and received three 20-second applications of laser irradiation or placebo " stimulation , " respectively . Pretreatment and posttreatment skin resistance and pain measurements ( via visual analog scale ) were taken during each session . Results indicated a statistically significant increase in skin resistance ( p less than .001 ) and a decrease in pain ( p less than .005 ) following laser treatment . There was not a significant correlation between skin resistance and pain across subjects . These data substantiate the previous findings of Snyder-Mackler and associates and demonstrate a reduction in pain . Helium-neon laser treatment , therefore , may be an effective adjunct to conventional physical therapy of these patients Seventy-seven patients with neck pain in the primary health care were included in a prospect i ve , r and omized clinical trial and r and omly assigned to general exercise , McKenzie treatment , or a control group . Seventy patients completed the treatment ; response rate 93 % at 12-month follow-up . All three groups showed significant improvement regarding the main outcomes , pain intensity and Neck Disability Index , even at 12-month follow-up , but there was no significant difference between the groups . In all , 79 % reported that they were better or completely restored after treatment , although 51 % reported constant/daily pain . In the McKenzie group compared with the control group , a tendency toward greater improvement was noted for pain intensity at 3 weeks and at 6-month follow-up , and for post-treatment Neck Disability Index . Significant improvement in Distress and Risk Assessment Method scores was shown in the McKenzie group only . The three groups had similar recurrence rates , although after 12 months the McKenzie group showed a tendency toward fewer visits for additional health care . The study did not provide a definite evidence of treatment efficacy in patients with neck pain , however , there was a tendency toward a better outcome with the two active alternatives compared with the control group Twenty-five out- patients with chronic neck pain participated in a prospect i ve , r and omized trial of acupuncture versus placebo transcutaneous nerve stimulation . A single-blind , non-cross-over design incorporated several outcome measures in an attempt to determine any particular facet of pain that responded to acupuncture . No significant difference between the two treatments was found either post-treatment or at follow-up . Whilst the small population studied limits the conclusions that may be drawn , these findings suggest that acupuncture may have no greater effect than that of a powerful placebo OBJECTIVES To compare the effects of real acupuncture to tender points for neck and shoulder pain and stiffness ( Japanese : katakori ) with those of sham acupuncture . DESIGN R and omized-controlled trial . METHODS Thirty-four volunteers from an acupuncture school with complaints of chronic pain and stiffness , who had no arm symptoms and gave informed consent , were r and omly allocated to acupuncture or sham groups . Acupuncture or sham acupuncture was applied to the tender points once a week for 3 weeks . In the acupuncture group the acupuncture needle was inserted to the muscle , then the sparrow pecking technique was applied five times . Sham acupuncture was done without insertion of the needle . Dull pain and stiffness were evaluated by visual analog scale ( VAS ) before , and every 2 days after the first needling for 1 month . Pressure pain threshold on the tender points was measured before and after each treatment . RESULTS There was no statistical difference of VAS scores between acupuncture and sham groups 9 days after the last treatment . However , the acupuncture group showed significant reduction of VAS scores immediately after and /or 1 day after the real acupuncture treatments ( P<0.01 ) . The effect tended to be prolonged after repeated treatment . Pressure pain thresholds tended to increase after real acupuncture treatment but not after sham acupuncture . CONCLUSIONS Acupuncture applied to tender points appears to have short-term effects on neck and shoulder pain and stiffness , but this study was unable to demonstrate any long-term superiority over sham acupuncture Abstract : Pain is a major symptom in cervical osteoarthritis ( COA ) . Low-power laser ( LPL ) therapy has been cl aim ed to reduce pain in musculoskeletal pathologies , but there have been concerns about this point . The aim of this study was to evaluate the analgesic efficacy of LPL therapy and related functional changes in COA . Sixty patients between 20 and 65 years of age with clinical ly and radiologically diagnosed COA were included in the study . They were r and omised into two equal groups according to the therapies applied , either with LPL or placebo laser . Patients in each group were investigated blindly in terms of pain and pain-related physical findings , such as increased paravertebral muscle spasm , loss of lordosis and range of neck motion restriction before and after therapy . Functional improvements were also evaluated . Pain , paravertebral muscle spasm , lordosis angle , the range of neck motion and function were observed to improve significantly in the LPL group , but no improvement was found in the placebo group . LPL seems to be successful in relieving pain and improving function in osteoarthritic diseases The analgesic-therapeutic efficacy and tolerability of a low-frequency electromagnetic field ( ELF ) , modulated at a frequency of 100 Hz with a sinusoidal waveform and mean induction of a few gauss , has been demonstrated by the authors in numerous previous studies of various hyperalgic pathologies , particularly of the locomotor apparatus . In the present study , the authors tested a new type of all-inclusive field , denoted TAMMEF , whose parameters ( frequency , intensity , waveform ) are modified in time , r and omly varying within the respective ranges , so that all the possible codes can occur during a single application . For the comparison , 150 subjects ( 118 women and 32 men , between 37 and 66 years of age ) were enrolled . They were affected by cervical spondylosis ( 101 cases ) or shoulder periarthritis ( 49 cases ) . Unbeknownst to them , they were r and omly divided into three groups of 50 subjects . One group was exposed to the new TAMMEF , another group to the usual ELF , and the third group to simulated treatment . The results show that the effects of the new TAMMEF therapy are equivalent to those obtained with the ELF STUDY DESIGN We conducted a nationally representative r and om household telephone survey to assess therapies used to treat back or neck pain . OBJECTIVES The main outcome was complementary therapies used in the last year to treat back or neck pain . SUMMARY OF BACKGROUND DATA Back pain and neck pain are common medical conditions that cause substantial morbidity . Despite the presumed importance of complementary therapies for these conditions , studies of care for back and neck pain have not gathered information about the use of complementary therapies . METHODS Our nationally representative survey sample d 2055 adults . The survey gathered detailed information about medical conditions , conventional and complementary therapies used to treat those conditions , and the perceived helpfulness of those therapies . RESULTS We found that of those reporting back or neck pain in the last 12 months , 37 % had seen a conventional provider and 54 % had used complementary therapies to treat their condition . Chiropractic , massage , and relaxation techniques were the most commonly used complementary treatments for back or neck pain ( 20 % , 14 % , and 12 % , respectively , of those with back or neck pain ) . Chiropractic , massage , and relaxation techniques were rated as " very helpful " for back or neck pain among users ( 61 % , 65 % , and 43 % , respectively ) , whereas conventional providers were rated as " very helpful " by 27 % of users . We estimate that nearly one-third of all complementary provider visits in 1997 ( 203 million of 629 million ) were made specifically for the treatment of back or neck pain . CONCLUSIONS Chiropractic , massage , relaxation techniques , and other complementary methods all play an important role in the care of patients with back or neck pain . Treatment for back and neck pain was responsible for a large proportion of all complementary provider visits made in 1997 . The frequent use and perceived helpfulness of commonly used complementary methods for these conditions warrant further investigation Study Design . A prospect i ve , multicenter , cross-sectional analysis of data from the National Spine Network data base . Objectives . To compare the relative impact of radicular and axial symptoms associated with disease of the cervical spine on general health as measured by the SF-36 Health Survey , and to compare the impact of these symptoms among patients of varying age and symptom duration . Background . Degenerative disorders of the cervical spine can cause debilitating symptoms of neck and arm pain . Physicians generally treat radiculopathy more aggressively than axial neck pain alone , although it has never been shown that the presence of radiculopathy leads to a greater impairment of physical and mental function . Material s and Methods . SF-36 Health Survey data were collected from all consenting patients seen within the National Spine Network . Patients with symptoms referable to the cervical spine ( as per their physician ) were included ( n = 1,809 ) . SF-36 scores for all eight scales ( bodily pain ( BP ) , vitality ( VT ) , general health ( GH ) , mental health ( MH ) , physical function ( PF ) , role physical ( RP ) , role emotional ( RE ) , and social function ( SF ) , and two summary scales ( Physical Component Summary [ PCS ] and Mental Component Summary [ MCS ] ) were calculated . Age/gender normative scores were subtracted from the scale scores to produce a negative “ impact ” score , which reflected how far below normal health status these patients were . Patients were grouped according to location of symptoms ( axial only , radicular only , or axial and radicular ) , age ( younger than 40 , 40 to 60 , and older than 60 years ) , and symptom duration ( acute : < 6 wk ; subacute : 6 wk–6 mo ; and chronic : > 6 mo ) . SF-36 scores were compared between all groups using analysis of variance and multiple comparisons with Bonferroni adjustment . Results . Patients who presented with both axial and radicular symptoms had the lowest SF-36 scores relative to age and gender norms . These scores were significantly lower than those for patients with only axial or only radicular symptoms across all eight subscales ( P < 0.05–P < 0.0001 ) . Scores for patients with only axial pain were significantly lower than for patients with only radicular pain for VT ( P < 0.04 ) and GH ( P < 0.004 ) . Patients younger than 40 and those between ages 40 to 60 years were significantly more impacted by their symptoms than patients older than 60 years for all eight scales ( P < 0.01 ) . PCS scores were similar for acute , subacute , and chronic groups , whereas MCS scores were significantly worse for patients with chronic pain . Conclusions . Combined neck and arm pain were much more disabling than either symptom alone . Younger patients ( younger than 40 or 40–60 ) were more affected by these symptoms than patients older than 60 years . In addition , as symptom duration increased , a negative impact on mental health was observed , although chronic symptoms did not affect physical health . This study suggests that patients with a significant component of axial pain in conjunction with cervical radiculopathy should be considered the most affected of all patients with cervical spondylosis . Given the evidence that the treatment methods at the disposal of physicians are effective , this study suggests that prompt treatment of these patients may help avoid the harmful effects of chronic symptoms on mental functioning , especially among younger patients who were found to be more impacted by the symptoms Study Design . A r and omized comparative study with single-blind outcome assessment s. Objectives . To compare the efficacy of a multimodal treatment emphasizing proprioceptive training ( ACTIVE ) with activated home exercises ( HOME ) and recommendation of exercise ( CONTROL ) in patients with nonspecific chronic neck pain . Summary of Background Data . The efficacy of active exercises and passive physiotherapy for neck trouble has been somewhat disappointing in the previous few studies . Methods . Seventy-six patients ( 22 men , 54 women ) with chronic , nonspecific neck pain participated . Sixty-two participated the 1-year follow-up . Subjective pain and disability , cervical ranges of motion , and pressure pain threshold in the shoulder region were measured at baseline , at 3 months , and at 12 months . The ACTIVE treatment consisted of 24 sessions of proprioceptive exercises , relaxation , and behavioral support . The HOME regimen included a neck lecture and two sessions of practical training for home exercises and instructions for maintaining a diary of progress . The CONTROL treatment included a lecture regarding care of the neck with a recommendation to exercise . Results . The average self-experienced total benefit was highest in the ACTIVE group , and the HOME group rated over the CONTROL group ( P < 0.001 ) . Differences between the groups in favor of the ACTIVE treatment were recorded in reduction of neck symptoms and improvements in general health and self-experienced working ability ( P < 0.01–0.03 ) . Changes in measures of mobility and pressure pain threshold were minor . Conclusions . Regarding self-experienced benefit , the multimodal treatment was more efficacious than activated home exercises that were clearly more efficacious than just advising . No major differences were noted in objective measurements of cervical function between the groups , but the content validity of these assessment s in chronic neck trouble can be question ed Cl aims have been made that local heat is particularly useful in treating osteoarthritis pain . This r and omised trial evaluates the short term efficacy of local heat , on the pain caused by cervical osteoarthrosis . Two treatment groups were compared , one receiving mock TNS and the other heat from an infra-red gun ( the IRS Medtec 100 ) . Both the placebo and treatment groups received treatment on local tender trigger points . Each patient received four treatments . Pain was assessed before entry into the trial and after the completion of treatment ; the parameters used for assessing pain were , analgesic intake , sleep disturbance due to pain and subjective pain score . Twenty-six patients were entered into the trial , twenty-five completed treatment . In the group receiving treatment from the infra-red gun ( IRS Medtec 100 ) 75 % obtained significant pain relief . In the group receiving mock TNS 31 % obtained significant pain relief . A chi-squared test comparing these two groups give a P value of 0.07 A cohort of3,342 cases constituting a r and om sample of all occupational back injuries compensated in Quebec ( Canada ) during 1981 was observed prospect ively for 3 years to study associations between cumulative duration of absence from work and sex , age , site of symptoms ( cervical , thoracic , and lumbar ) , and occupation . Of the cohort members , 287 ( 9.7 % ) cumulated 6 months of absence or more . A logistic regression model showed age and site of symptoms to be the two most important risk factors associated with absences of 6 months or more . No association was found with sex or occupation . The results showed discrepancies between measures of frequency distribution of back injuries and duration of absence from work , an important finding in terms of identifying health priorities Study Design A r and omized cross-sectional question naire was used to determine the prevalence of neck pain in Norwegian adults . Objectives The frequency and duration of neck pain were assessed . Summary of Background Data Reliable epidemiologic studies on the prevalence of neck pain in the general population have been sparse . Methods A question naire that inquired about neck pain within the last year was sent to a r and om sample of 10,000 adult Norwegians . Results Overall , 34.4 % of the responders had experienced neck pain within the last year . A total of 13.8 % reported neck pain that lasted for more than 6 months . Conclusions Chronic neck pain is a frequent symptom in the general population , particularly in women . Although reservations have to be taken as to the interpretation , the reported prevalence of persisting pain after whiplash injuries is of the same magnitude as the prevalence of chronic neck pain in the general population Head repositioning accuracy ( HRA ) after full range active motion was evaluated in 60 cervicalgic patients . The mean angular error was 7.7 degrees + /- 3.3 ( mean + /- SD ) and 82 % were outside a threshold value of 4.5 degrees . After r and omization 30 patients followed a rehabilitation program based on eye-head coupling ( RG ) and 30 served as a control group ( CG ) . At 10 week follow-up , a greater gain in HRA was observed in the RG ( 2 degrees + /- 2.7 , mean + /- SD ) than in the CG ( 0 + /- 2.6 , mean + /- SD ) ( p = 0.005 ) . Clinical parameters ( pain , drug intake , range of motion , and self assessed functional improvement ) were also more improved in the RG than in the CG . These data emphasize the role of a neck proprioception alteration in chronic neck pain and suggest that a rehabilitation program based on eye-head coupling should be included in most medical management of cervicalgic patients In a controlled , cross-over study the effect of low level laser therapy ( LLLT ) was evaluated . During a five weeks period forty-seven female laboratory technicians received six laser and six placebo treatments to tender points in the neck and shoulder girdle . Subjects rated the placebo treatment significantly more beneficial than LLLT ( p = .04 ) . There was no reduction in consumption of analgesics associated with either laser or placebo treatment . The results indicate no beneficial effect of LLLT for myofascial pain Abstract The effect of exercise on neck – shoulder pain was studied in 103 women with work‐related trapezius myalgia r and omized into three exercise groups and a control group . One group trained strength , the second muscular endurance and the third co‐ordination . The exercise groups met three times weekly for 10 weeks . Pain assessment was made on three visual analogue scales , indicating pain at present , pain in general and pain at worst . Pain thresholds were measured in the trapezius muscle with a pressure algometer . A pain drawing was completed . The rated pain decreased significantly ( P<0.05 ) on the VAS describing pain at worst in the strength and endurance groups . Pressure sensitivity decreased significantly ( P<0.05 ) in four triggerpoints in the exercise groups . No changes were seen in the extent of painful body area in any group . Comparison of exercisers ( n=82 ) and controls ( n=21 ) showed significantly larger pain reductions on VAS pain at present and VAS pain at worst among exercisers . All three exercise programs showed similar decreases of pain which indicates that the type of exercise is of less importance to achieve pain reduction The objective of the investigation was to study the course of neck and shoulder symptoms and the predictors for these symptoms among women in light sedentary work . Postal surveys were conducted among 351 tellers ( age 20 - 50 years ) of a bank company in September , December , March , and May. The response rates were 74 - 90 % . The outcome was the frequency of the symptoms during the previous three months . In the analysis , univariate explorations and r and om-effects logistic binomial regression for distinguishable responses were used . A change in the frequency of neck and shoulder symptoms was seen in 40.5 % of the subjects during the follow-up period from autumn to spring . The frequency of the symptoms decreased from autumn and winter towards spring . The stability of the frequency of the symptoms was positively associated with age . Seasonal variation in symptoms should be considered when preventive programs against neck and shoulder disorders are planned and evaluated Thirty patients with cervical spine pain syndromes persisting a mean of 8 years were assigned r and omly into equal treatment and control groups . After 12 weeks , 12 of 15 ( 80 % ) of the treated group felt improved , some dramatically , with a mean 40 % reduction of pain score , 54 % reduction of pain pills , 68 % reduction of pain hours per day and 32 % less limitation of activity . Two of 15 ( 13 % ) of the control group reported slight improvement after 12.8 weeks . The control group had a mean 2 % worsening of the pain score , 10 % reduction in pain pills , no lessening of pain hours and 12 % less limitation of activity The effect of " neck school " on neck and shoulder disorders was studied in medical secretaries . A neck school reinforced with compliance enhancing measures ( group B ) was compared with a traditional neck school ( group A ) and a control group ( group C ) . The results show that ergonomical knowledge was good even before the secretaries attended the neck schools and that compliance was significantly higher for group B. When comparisons were made within groups some improvements on neck and shoulder fatigue and pain were noted , particularly for group B. When workload was controlled no significant group differences were found . No differences were noted for range of neck motion , or sick leave in any group . Our conclusion is that neck schools , despite good compliance , appear to be of limited clinical value for prevention of neck and shoulder disorders |
12,449 | 21,944,658 | CONCLUSIONS It is concluded that yoga has the potential for alleviating pain . | OBJECTIVE The objective of this systematic review was to assess the effectiveness of yoga as a treatment option for any type of pain . | BACKGROUND There has been limited study of yoga training as a complementary exercise strategy to manage the symptom of dyspnea in patients with chronic obstructive pulmonary disease ( COPD ) . PURPOSE The primary purpose of this pilot study was to evaluate a yoga program for its safety , feasibility , and efficacy for decreasing dyspnea intensity ( DI ) and dyspnea-related distress ( DD ) in older adults with COPD . METHODS Clinical ly stable patients with COPD ( n = 29 ; age 69.9 + /- 9.5 ; forced expiratory volume in 1 second ( FEV(1 ) ) 47.7 + /- 15.6 % predicted ; female = 21 ) were r and omized to a 12-week yoga program specifically design ed for people with COPD or usual-care control ( UC ) . The twice-weekly yoga program included asanas ( yoga postures ) and visama vritti pranayama ( timed breathing ) . Safety measure outcomes included heart rate , oxygen saturation , dyspnea , and pain . Feasibility was measured by patient-reported enjoyment , difficulty , and adherence to yoga sessions . At baseline and at 12 weeks , DI and DD were measured during incremental cycle ergometry and a 6-minute walk ( 6MW ) test . Secondary efficacy outcomes included physical performance , psychologic well-being , and health-related quality of life ( HRQoL ) . RESULTS Yoga training was safe and feasible for patients with COPD . While yoga training had only small effects on DI after the 6MW test ( effect size [ ES ] , 0.20 ; p = 0.60 ) , there were greater reductions in DD in the yoga group compared to UC ( ES , 0.67 ; p = 0.08 ) . Yoga training also improved 6MW distance ( + 71.7 + /- 21.8 feet versus -27.6 + /- 36.2 feet ; ES = 0.78 , p = 0.04 ) and self-reported functional performance ( ES = 0.79 , p = 0.04 ) compared to UC . There were small positive changes in muscle strength and HRQoL. CONCLUSIONS Elderly patients with COPD participated safely in a 12-week yoga program especially design ed for patients with this chronic illness . After the program , the subjects tolerated more activity with less DD and improved their functional performance . These findings need to be confirmed in a larger , more sufficiently powered efficacy study The aim of this study was to measure the effects of a bi-weekly Raj yoga program on rheumatoid arthritis ( RA ) disease activity . Subjects were recruited from among RA patients in Dubai , United Arab Emirates by email invitations of the RA data base . Demographic data , disease activity indices , health assessment question naire ( HAQ ) , and quality of life ( QOL ) by SF-36 were documented at enrollment and after completion of 12 sessions of Raj yoga . A total of 47 patients were enrolled : 26 yoga and 21 controls . Baseline demographics were similar in both groups . Patients who underwent yoga had statistically significant improvements in DAS28 and HAQ , but not QOL . Our pilot study of 12 sessions of yoga for RA was able to demonstrate statistically significant improvements in RA disease parameters . We believe that a longer duration of treatment could result in more significant improvements AIM To evaluate the effects of a yoga-based exercise program on pain , fatigue , sleep disturbance , and biochemical markers in hemodialysis patients . MATERIAL S AND METHODS In 2004 a r and omized controlled trial was carried out in the outpatient hemodialysis unit of the Nephrology Department , Uludag University Faculty of Medicine . Clinical ly stable hemodialysis patients ( n=37 ) were included and followed in two groups : the modified yoga-based exercise group ( n=19 ) and the control group ( n=18 ) . Yoga-based exercises were done in groups for 30 min/day twice a week for 3 months . All of the patients in the yoga and control groups were given an active range of motion exercises to do for 10 min at home . The main outcome measures were pain intensity ( measured by the visual analogue scale , VAS ) , fatigue ( VAS ) , sleep disturbance ( VAS ) , and grip strength ( mmHg ) ; biochemical variables-- urea , creatinine , calcium , alkaline phosphatase , phosphorus , cholesterol , HDL-cholesterol , triglyceride , erythrocyte , hematocrit -- were evaluated . RESULTS After a 12-week intervention , significant improvements were seen in the variables : pain -37 % , fatigue -55 % , sleep disturbance -25 % , grip strength + 15 % , urea -29 % , creatinine -14 % , alkaline phosphatase -15 % , cholesterol -15 % , erythrocyte + 11 % , and hematocrit count + 13 % ; no side-effects were seen . Improvement of the variables in the yoga-based exercise program was found to be superior to that in the control group for all the variables except calcium , phosphorus , HDL-cholesterol and triglyceride levels . CONCLUSION A simplified yoga-based rehabilitation program is a complementary , safe and effective clinical treatment modality in patients with end-stage renal disease BACKGROUND Adolescents with irritable bowel syndrome ( IBS ) frequently experience interference with everyday activities . Mind-body approaches such as yoga have been recommended as interventions for patients with IBS . Despite promising results among adult sample s , there have been limited studies exploring the efficacy of yoga with pediatric patients . OBJECTIVE To conduct a preliminary r and omized study of yoga as treatment for adolescents with IBS . METHODS Twenty-five adolescents aged 11 to 18 years with IBS were r and omly assigned to either a yoga or wait list control group . Before the intervention , both groups completed question naires assessing gastrointestinal symptoms , pain , functional disability , coping , anxiety and depression . The yoga intervention consisted of a 1 h instructional session , demonstration and practice , followed by four weeks of daily home practice guided by a video . After four weeks , adolescents repeated the baseline question naires . The wait list control group then received the yoga intervention and four weeks later completed an additional set of question naires . RESULTS Adolescents in the yoga group reported lower levels of functional disability , less use of emotion-focused avoidance and lower anxiety following the intervention than adolescents in the control group . When the pre- and postintervention data for the two groups were combined , adolescents had significantly lower scores for gastrointestinal symptoms and emotion-focused avoidance following the yoga intervention . Adolescents found the yoga to be helpful and indicated they would continue to use it to manage their IBS . CONCLUSIONS Yoga holds promise as an intervention for adolescents with IBS This study examined the effects of a yoga program during pregnancy , on maternal comfort , labor pain , and birth outcomes . A r and omized trial was conducted using 74-primigravid Thai women who were equally divided into two groups ( experimental and control ) . The yoga program involved six , 1-h sessions at prescribed weeks of gestation . A variety of instruments were used to assess maternal comfort , labor pain and birth outcomes . The experimental group was found to have higher levels of maternal comfort during labor and 2h post-labor , and experienced less subject evaluated labor pain than the control group . In each group , pain increased and maternal comfort decreased as labor progressed . No differences were found , between the groups , regarding pethidine usage , labor augmentation or newborn Apgar scores at 1 and 5 min . The experimental group was found to have a shorter duration of the first stage of labor , as well as the total time of labor The present study has been conducted to evaluate selected yogic procedures on individuals with low back pain . The underst and ing of back pain as one of the commonest clinical presentations during clinical practice made the path to the present study . It has also been calculated that more than three-quarters of the world 's population experience back pain at some time in their lives . Twelve patients were selected and r and omly divided into two groups , viz . , group A yogic group and group B control group . Advice for life style and diet was given for all the patients . The effect of the therapy was assessed subjectively and objective ly . Particular scores drawn for yogic group and control group were individually analyzed before and after treatment and the values were compared using st and ard statistical protocol s. Yogic intervention revealed 79 % relief in both subjective and objective parameters ( i.e. , 7 out of 14 parameters showed statistically highly significant P < 0.01 results , while 4 showed significant results P < 0.05 ) . Comparative effect of yogic group and control group showed 79 % relief in both subjective and objective parameters . ( i.e. , total 6 out of 14 parameters showed statistically highly significant ( P < 0.01 ) results , while 5 showed significant results ( P < 0.05 ) Context Yoga combines exercise with achieving a state of mental focus through breathing . In the United States , 1 million people practice yoga for low back pain . Contribution The authors recruited patients who had a recent primary care visit for low back pain and r and omly assigned 101 to yoga or conventional exercise or a self-care book . Patients in the yoga and exercise groups reported good adherence at 26 weeks . Compared with self-care , symptoms were milder and function was better with yoga . The exercise group had intermediate outcomes . Symptoms improved between 12 and 26 weeks only with yoga . Implication s Yoga was a more effective treatment for low back pain than a self-care book . The Editors Most treatments for chronic low back pain have modest efficacy at best ( 1 ) . Exercise is one of the few proven treatments for chronic low back pain ; however , its effects are often small , and no form has been shown to be clearly better than another ( 2 - 5 ) . Yoga , which often couples physical exercise with breathing , is a popular alternative form of mindbody therapy . An estimated 14 million Americans practice d yoga in 2002 ( 6 ) , including more than 1 million who used it as a treatment for back pain ( 7 , 8) . Yoga may benefit patients with back pain simply because it involves exercise or because of its effects on mental focus . We found no published studies in western biomedical literature that evaluated yoga for chronic low back pain ; therefore , we design ed a clinical trial to evaluate its effectiveness and safety for this condition . Methods Study Design and Setting This r and omized , controlled trial compared the effects of yoga classes with conventional exercise classes and with a self-care book in patients with low back pain that persisted for at least 12 weeks . The study was conducted at Group Health Cooperative , a nonprofit , integrated health care system with approximately 500000 enrollees in Washington State and Idaho . The Group Health Cooperative institutional review board approved the study protocol , and all study participants gave oral informed consent before the eligibility screening and written consent before the baseline interview and r and omization . Patients Patients from Group Health Cooperative were recruited for 12-week sessions of classes that were conducted between June and December 2003 . We mailed letters describing the study to 6913 patients between 20 and 64 years of age who had visited a primary care provider for treatment of back pain 3 to 15 months before the study ( according to electronic visit records ) . We also advertised the study in the health plan 's consumer magazine . Patients were informed that we were comparing 3 approaches for the relief of back pain and that each was design ed to help reduce the negative effects of low back pain on people 's lives . A research assistant telephoned patients who returned statements of interest to assess their eligibility . After we received their signed informed consent forms , eligible patients were telephoned again for collection of baseline data and r and omization to treatment . We excluded individuals whose back pain was complicated ( for example , sciatica , previous back surgery , or diagnosed spinal stenosis ) , potentially attributable to specific underlying diseases or conditions ( for example , pregnancy , metastatic cancer , spondylolisthesis , fractured bones , or dislocated joints ) , or minimal ( rating of less than 3 on a bothersomeness scale of 0 to 10 ) . We also excluded individuals who were currently receiving other back pain treatments or had participated in yoga or exercise training for back pain in the past year , those with a possible disincentive to improve ( such as patients receiving workers ' compensation or those involved in litigation ) , and those with unstable medical or severe psychiatric conditions or dementia . Patients who had contraindications ( for example , symptoms consistent with severe disk disease ) or schedules that precluded class participation , those who were unwilling to practice at home , or those who could not speak or underst and English were also excluded . R and omization Protocol Participants were r and omly assigned to participate in yoga or exercise classes or to receive the self-care book . We r and omly generated treatment assignments for each class series by using a computer program with block sizes of 6 or 9 . A research er who was not involved in patient recruitment or r and omization placed the assignments in opaque , sequentially numbered envelopes , which were stored in a locked filing cabinet until needed for r and omization . Interventions The yoga and exercise classes developed specifically for this study consisted of 12 weekly 75-minute classes design ed to benefit people with chronic low back pain . In addition to attending classes held at Group Health facilities , participants were asked to practice daily at home . Participants received h and outs that described home practice s , and yoga participants received auditory compact discs to guide them through the sequence of postures with the appropriate mental focus ( examples of postures are shown in the Appendix Figure ) . Study participants retained access to all medical care provided by their insurance plan . Appendix Figure . Yoga postures Yoga We chose to use viniyoga , a therapeutically oriented style of yoga that emphasizes safety and is relatively easy to learn . Our class instructor and a senior teacher of viniyoga , who has + written a book about its therapeutic uses ( 9 ) , design ed the yoga intervention for patients with back pain who did not have previous yoga experience . Although all the sessions emphasized use of postures and breathing for managing low back symptoms , each had a specific focus : relaxation ; strength-building , flexibility , and large-muscle movement ; asymmetric poses ; strengthening the hip muscles ; lateral bending ; integration ; and customizing a personal practice . The postures were selected from a core of 17 relatively simple postures , some with adaptations ( Appendix Table ) , and the sequence of the postures in each class was performed according to the rudiments of viniyoga ( 9 ) . Each class included a question - and -answer period , an initial and final breathing exercise , 5 to 12 postures , and a guided deep relaxation . Most postures were not held but were repeated 3 or 6 times . Exercise Because we could not identify a clearly superior form of therapeutic exercise for low back pain from the literature , a physical therapist design ed a 12-session class series that was 1 ) different from what most participants would have probably experienced in previous physical therapy sessions ( to maximize adherence ) and 2 ) similar to the yoga classes in number and length . We included a short educational talk that provided information on proper body mechanics , the benefits of exercise and realistic goal setting , and overcoming common barriers to developing an exercise routine ( for example , fear ) . Each session began with the educational talk ; feedback from the previous week ; simple warm-ups to increase heart rate ; and repetitions of a series of 7 aerobic exercises and 10 strengthening exercises that emphasized leg , hip , abdominal , and back muscles . Over the course of the 12-week series , the number of repetitions of each aerobic and strength exercise increased from 8 to 30 in increments of 2 . The strengthening exercises were followed by 12 stretches for the same muscle groups ; each stretch was held for 30 seconds . Classes ended with a short , unguided period of deep , slow breathing . Self-Care Book Participants were mailed a copy of The Back Pain Helpbook ( 10 ) , an evidence -based book that emphasized such self-care strategies as adoption of a comprehensive fitness and strength program , appropriate lifestyle modification , and guidelines for managing flare-ups . Although we did not provide any instructions for using the book , many of the chapters concluded with specific action items . Outcome Measures Interviewers who were masked to the treatment assignments conducted telephone interviews at baseline and at 6 , 12 , and 26 weeks after r and omization . The baseline interview collected information regarding sociodemographic characteristics , back pain history , and the participant 's level of knowledge about yoga and exercise . Participants were asked to describe their current pain and to rate their expectations for each intervention . The primary outcomes were back-related dysfunction and symptoms , and the primary time point of interest was 12 weeks . We used the modified Rol and Disability Scale ( 11 ) to measure patient dysfunction by totaling the number of positive responses to 23 questions about limitations of daily activities that might arise from back pain . This scale has been found to be valid , reliable , and sensitive to change ( 12 - 14 ) ; research ers estimate that the minimum clinical ly significant difference on the Rol and scale ranges from 2 to 3 points ( 13 , 15 ) . Participants rated how bothersome their back pain had been during the previous week on an 11-point scale , in which 0 represented not at all bothersome and 10 represented extremely bothersome ; a similar measure demonstrated substantial construct validity in earlier research ( 13 ) . Estimates of the minimum clinical ly significant difference on the bothersomeness scale were approximately 1.5 points ( 16 , 17 ) . Secondary outcome measures were general health status , which we assessed by conducting the Short Form-36 Health Survey ( 18 ) ; degree of restricted activity as determined by patient responses to 3 questions ( 19 ) ; and medication use . After all outcomes data were collected , we asked questions related to specific interventions ( for example , Did you practice at home ? ) . At the 12-week interview , we asked class participants about any pain or substantial discomfort they experienced as a result of the classes . We assessed adherence to the home practice recommendations by asking class participants to complete weekly home practice logs and by asking about home practice during the follow-up Low back pain is a significant public health problem and one of the most commonly reported reasons for the use of Complementary Alternative Medicine . A r and omized control trial was conducted in subjects with non‐specific chronic low back pain comparing Iyengar yoga therapy to an educational control group . Both programs were 16 weeks long . Subjects were primarily self‐referred and screened by primary care physicians for study of inclusion /exclusion criteria . The primary outcome for the study was functional disability . Secondary outcomes including present pain intensity , pain medication usage , pain‐related attitudes and behaviors , and spinal range of motion were measured before and after the interventions . Subjects had low back pain for 11.2±1.54 years and 48 % used pain medication . Overall , subjects presented with less pain and lower functional disability than subjects in other published intervention studies for chronic low back pain . Of the 60 subjects enrolled , 42 ( 70 % ) completed the study . Multivariate analyses of outcomes in the categories of medical , functional , psychological and behavioral factors indicated that significant differences between groups existed in functional and medical outcomes but not for the psychological or behavioral outcomes . Univariate analyses of medical and functional outcomes revealed significant reductions in pain intensity ( 64 % ) , functional disability ( 77 % ) and pain medication usage ( 88 % ) in the yoga group at the post and 3‐month follow‐up assessment s. These preliminary data indicate that the majority of self‐referred persons with mild chronic low back pain will comply to and report improvement on medical and functional pain‐related outcomes from Iyengar yoga therapy OBJECTIVE The aim of this study was to compare the effect of a short-term intensive residential yoga program with physical exercise ( control ) on pain and spinal flexibility in subjects with chronic low-back pain ( CLBP ) . DESIGN This was a wait-list , r and omized controlled study . SETTING The study was conducted at a residential integrative health center in Bangalore , South India . SUBJECTS Eighty ( 80 ) subjects ( females , n = 37 ) with CLBP , who consented were r and omly assigned to receive yoga or physical exercise if they satisfied the selection criteria . INTERVENTION The intervention consisted of a 1-week intensive residential yoga program comprised of asanas ( physical postures ) design ed for back pain , pranayamas ( breathing practice s ) , meditation , and didactic and interactive sessions on philosophical concepts of yoga . The control group practice d physical exercises under a trained physiatrist and also had didactic and interactive sessions on lifestyle change . Both of the groups were matched for time on intervention and attention . OUTCOME MEASURES Pain-related outcomes were assessed by the Oswestry Disability Index ( ODI ) and by spinal flexibility , which was assessed using goniometer at pre and post intervention . Data were analyzed using repeated measures analysis of variance ( RMANOVA ) . RESULTS Data conformed to a Gaussian distribution . There was a significant reduction in ODI scores in the yoga group compared to the control group ( p = 0.01 ; effect size 1.264 ) . Spinal flexibility measures improved significantly in both groups but the yoga group had greater improvement as compared to controls on spinal flexion ( p = 0.008 ; effect size 0.146 ) , spinal extension ( p = 0.002 ; effect size 0.251 ) , right lateral flexion ( p = 0.059 ; effect size 0.006 ) ; and left lateral flexion ( p = 0.006 ; effect size 0.171 ) . CONCLUSIONS Seven ( 7 ) days of a residential intensive yoga-based lifestyle program reduced pain-related disability and improved spinal flexibility in patients with CLBP better than a physical exercise regimen BACKGROUND Numerous studies have explored the effectiveness of complementary and alternative medicine in the treatment of migraine but there is no documented investigation of the effectiveness of yoga therapy for migraine management . OBJECTIVES To investigate the effectiveness of holistic approach of yoga therapy for migraine treatment compared to self-care . DESIGN A r and omized controlled trial . METHODS Seventy-two patients with migraine without aura were r and omly assigned to yoga therapy or self-care group for 3 months . Primary outcomes were headache frequency ( headache diary ) , severity of migraine ( 0 - 10 numerical scale ) and pain component ( McGill pain question naire ) . Secondary outcomes were anxiety and depression ( Hospital anxiety depression scale ) , medication score . RESULTS After adjustment for baseline values , the subjects ' complaints related to headache intensity ( P < .001 ) , frequency ( P < .001 ) , pain rating index ( P < .001 ) , affective pain rating index ( P < .001 ) , total pain rating index ( P < .001 ) , anxiety and depression scores ( P < .001 ) , symptomatic medication use ( P < .001 ) were significantly lower in the yoga group compared to the self-care group . CONCLUSION The study demonstrated a significant reduction in migraine headache frequency and associated clinical features , in patients treated with yoga over a period of 3 months . Further study of this therapeutic intervention appears to be warranted PURPOSE The purpose of this r and omized pilot study was to evaluate a possible design for a 6-week modified hatha yoga protocol to study the effects on participants with chronic low back pain . PARTICIPANTS Twenty-two participants ( M = 4 ; F = 17 ) , between the ages of 30 and 65 , with chronic low back pain ( CLBP ) were r and omized to either an immediate yoga based intervention , or to a control group with no treatment during the observation period but received later yoga training . METHODS A specific CLBP yoga protocol design ed and modified for this population by a certified yoga instructor was administered for one hour , twice a week for 6 weeks . Primary functional outcome measures included the forward reach ( FR ) and sit and reach ( SR ) tests . All participants completed Oswestry Disability Index ( ODI ) and Beck Depression Inventory ( BDI ) question naires . Guiding questions were used for qualitative data analysis to ascertain how yoga participants perceived the instructor , group dynamics , and the impact of yoga on their life . ANALYSIS To account for drop outs , the data were divided into better or not categories , and analyzed using chi-square to examine differences between the groups . Qualitative data were analyzed through frequency of positive responses . RESULTS Potentially important trends in the functional measurement scores showed improved balance and flexibility and decreased disability and depression for the yoga group but this pilot was not powered to reach statistical significance . Significant limitations included a high dropout rate in the control group and large baseline differences in the secondary measures . In addition , analysis of the qualitative data revealed the following frequency of responses ( 1 ) group intervention motivated the participants and ( 2 ) yoga fostered relaxation and new awareness/learning . CONCLUSION A modified yoga-based intervention may benefit individuals with CLB , but a larger study is necessary to provide definitive evidence . Also , the impact on depression and disability could be considered as important outcomes for further study . Additional functional outcome measures should be explored . This pilot study supports the need for more research investigating the effect of yoga for this population BACKGROUND Emotional distress is an increasing public health problem and Hatha yoga has been cl aim ed to induce stress reduction and empowerment in practicing subjects . We aim ed to evaluate potential effects of Iyengar Hatha yoga on perceived stress and associated psychological outcomes in mentally distressed women . MATERIAL / METHODS A controlled prospect i ve non-r and omized study was conducted in 24 self-referred female subjects ( mean age 37.9+/-7.3 years ) who perceived themselves as emotionally distressed . Subjects were offered participation in one of two subsequential 3-months yoga programs . Group 1 ( n=16 ) participated in the first class , group 2 ( n=8 ) served as a waiting list control . During the yoga course , subjects attended two-weekly 90-min Iyengar yoga classes . Outcome was assessed on entry and after 3 months by Cohen Perceived Stress Scale , State-Trait Anxiety Inventory , Profile of Mood States , CESD-Depression Scale , Bf-S/Bf-S ' Well-Being Scales , Freiburg Complaint List and ratings of physical well-being . Salivary cortisol levels were measured before and after an evening yoga class in a second sample . RESULTS Compared to waiting-list , women who participated in the yoga-training demonstrated pronounced and significant improvements in perceived stress ( P<0.02 ) , State and Trait Anxiety ( P<0.02 and P<0.01 , respectively ) , well-being ( P<0.01 ) , vigor ( P<0.02 ) , fatigue ( P<0.02 ) and depression ( P<0.05 ) . Physical well-being also increased ( P<0.01 ) , and those subjects suffering from headache or back pain reported marked pain relief . Salivary cortisol decreased significantly after participation in a yoga class ( P<0.05 ) . CONCLUSIONS Women suffering from mental distress participating in a 3-month Iyengar yoga class show significant improvements on measures of stress and psychological outcomes . Further investigation of yoga with respect to prevention and treatment of stress-related disease and of underlying mechanism is warranted Goal of workBreast cancer survivors have limited options for the treatment of hot flashes and related symptoms . Further , therapies widely used to prevent recurrence in survivors , such as tamoxifen , tend to induce or exacerbate menopausal symptoms . The aim of this preliminary , r and omized controlled trial was to evaluate the effects of a yoga intervention on menopausal symptoms in a sample of survivors of early-stage breast cancer ( stages IA – IIB ) . Material s and methods Thirty-seven disease-free women experiencing hot flashes were r and omized to the 8-week Yoga of Awareness program ( gentle yoga poses , meditation , and breathing exercises ) or to wait-list control . The primary outcome was daily reports of hot flashes collected at baseline , posttreatment , and 3 months after treatment via an interactive telephone system . Data were analyzed by intention to treat . Main results At posttreatment , women who received the yoga program showed significantly greater improvements relative to the control condition in hot-flash frequency , severity , and total scores and in levels of joint pain , fatigue , sleep disturbance , symptom-related bother , and vigor . At 3 months follow-up , patients maintained their treatment gains in hot flashes , joint pain , fatigue , symptom-related bother , and vigor and showed additional significant gains in negative mood , relaxation , and acceptance . Conclusions This pilot study provides promising support for the beneficial effects of a comprehensive yoga program for hot flashes and other menopausal symptoms in early-stage breast cancer survivors BACKGROUND Several studies suggest yoga may be effective for chronic low back pain ; however , trials targeting minorities have not been conducted . PRIMARY STUDY OBJECTIVES : Assess the feasibility of study ing yoga in a predominantly minority population with chronic low back pain . Collect preliminary data to plan a larger powered study . STUDY DESIGN Pilot r and omized controlled trial . SETTING Two community health centers in a racially diverse neighborhood of Boston , Massachusetts . PARTICIPANTS Thirty English-speaking adults ( mean age 44 years , 83 % female , 83 % racial/ethnic minorities ; 48 % with incomes < or = $ 30,000 ) with moderate-to-severe chronic low back pain . INTERVENTIONS St and ardized series of weekly hatha yoga classes for 12 weeks compared to a waitlist usual care control . OUTCOME MEASURES Feasibility measured by time to complete enrollment , proportion of racial/ethnic minorities enrolled , retention rates , and adverse events . Primary efficacy outcomes were changes from baseline to 12 weeks in pain score ( 0=no pain to 10=worst possible pain ) and back-related function using the modified Rol and -Morris Disability Question naire ( 0 - 23 point scale , higher scores reflect poorer function ) . Secondary efficacy outcomes were analgesic use , global improvement , and quality of life ( SF-36 ) . RESULTS Recruitment took 2 months . Retention rates were 97 % at 12 weeks and 77 % at 26 weeks . Mean pain scores for yoga decreased from baseline to 12 weeks ( 6.7 to 4.4 ) compared to usual care , which decreased from 7.5 to 7.1 ( P=.02 ) . Mean Rol and scores for yoga decreased from 14.5 to 8.2 compared to usual care , which decreased from 16.1 to 12.5 ( P=.28 ) . At 12 weeks , yoga compared to usual care participants reported less analgesic use ( 13 % vs 73 % , P=.003 ) , less opiate use ( 0 % vs 33 % , P=.04 ) , and greater overall improvement ( 73 % vs 27 % , P=.03 ) . There were no differences in SF-36 scores and no serious adverse events . CONCLUSION A yoga study intervention in a predominantly minority population with chronic low back pain was moderately feasible and may be more effective than usual care for reducing pain and pain medication use OBJECTIVE To examine the feasibility and level of acceptability of a mindful yoga intervention provided during pregnancy and to gather preliminary data on the efficacy of the intervention in reducing distress . DESIGN Baseline and post-treatment measures examined state and trait anxiety , perceived stress , pain , and morning salivary cortisol in a single treatment group . Postintervention data also included participant evaluation of the intervention . SETTING The 7 weeks mindfulness-based yoga group intervention combined elements of Iyengar yoga and mindfulness-based stress reduction . PARTICIPANTS Sixteen healthy pregnant nulliparous women with singleton pregnancies between 12 and 32 weeks gestation at the time of enrollment . METHODS Outcomes were evaluated from pre- to postintervention and between second and third trimesters with repeated measures analysis of variance and post hoc nonparametric tests . RESULTS Women practicing mindful yoga in their second trimester reported significant reductions in physical pain from baseline to postintervention compared with women in the third trimester whose pain increased . Women in their third trimester showed greater reductions in perceived stress and trait anxiety . CONCLUSIONS Preliminary evidence supports yoga 's potential efficacy in these areas , particularly if started early in the pregnancy OBJECTIVE Yoga and relaxation techniques have traditionally been used by nonmedical practitioners to help alleviate musculoskeletal symptoms . The objective of this study was to collect controlled observations of the effect of yoga on the h and s of patients with osteoarthritis ( OA ) . METHODS Patients with OA of the h and s were r and omly assigned to receive either the yoga program or no therapy . Yoga techniques were supervised by one instructor once/week for 8 weeks . Variables assessed were pain , strength , motion , joint circumference , tenderness , and h and function using the Stanford H and Assessment question naire . RESULTS The yoga treated group improved significantly more than the control group in pain during activity , tenderness and finger range of motion . Other trends also favored the yoga program . CONCLUSION This yoga derived program was effective in providing relief in h and OA . Further studies are needed to compare this with other treatments and to examine longterm effects CONTEXT Carpal tunnel syndrome is a common complication of repetitive activities and causes significant morbidity . OBJECTIVE To determine the effectiveness of a yoga-based regimen for relieving symptoms of carpal tunnel syndrome . DESIGN R and omized , single-blind , controlled trial . SETTING A geriatric center and an industrial site in 1994 - 1995 . PATIENTS Forty-two employed or retired individuals with carpal tunnel syndrome ( median age , 52 years ; range , 24 - 77 years ) . INTERVENTION Subjects assigned to the yoga group received a yoga-based intervention consisting of 11 yoga postures design ed for strengthening , stretching , and balancing each joint in the upper body along with relaxation given twice weekly for 8 weeks . Patients in the control group were offered a wrist splint to supplement their current treatment . MAIN OUTCOME MEASURES Changes from baseline to 8 weeks in grip strength , pain intensity , sleep disturbance , Phalen sign , and Tinel sign , and in median nerve motor and sensory conduction time . RESULTS Subjects in the yoga groups had significant improvement in grip strength ( increased from 162 to 187 mm Hg ; P = .009 ) and pain reduction ( decreased from 5.0 to 2.9 mm ; P = .02 ) , but changes in grip strength and pain were not significant for control subjects . The yoga group had significantly more improvement in Phalen sign ( 12 improved vs 2 in control group ; P = .008 ) , but no significant differences were found in sleep disturbance , Tinel sign , and median nerve motor and sensory conduction time . CONCLUSION In this preliminary study , a yoga-based regimen was more effective than wrist splinting or no treatment in relieving some symptoms and signs of carpal tunnel syndrome Study Design . The effectiveness and efficacy of Iyengar yoga for chronic low back pain ( CLBP ) were assessed with intention-to-treat and per- protocol analysis . Ninety subjects were r and omized to a yoga ( n = 43 ) or control group ( n = 47 ) receiving st and ard medical care . Participants were followed 6 months after completion of the intervention . Objective . This study aim ed to evaluate Iyengar yoga therapy on chronic low back pain . Yoga subjects were hypothesized to report greater reductions in functional disability , pain intensity , depression , and pain medication usage than controls . Summary of Background Data . CLBP is a musculoskeletal disorder with public health and economic impact . Pilot studies of yoga and back pain have reported significant changes in clinical ly important outcomes . Methods . Subjects were recruited through self-referral and health professional referrals according to explicit inclusion /exclusion criteria . Yoga subjects participated in 24 weeks of biweekly yoga classes design ed for CLBP . Outcomes were assessed at 12 ( midway ) , 24 ( immediately after ) , and 48 weeks ( 6-month follow-up ) after the start of the intervention using the Oswestry Disability Question naire , a Visual Analog Scale , the Beck Depression Inventory , and a pain medication-usage question naire . Results . Using intention-to-treat analysis with repeated measures ANOVA ( group × time ) , significantly greater reductions in functional disability and pain intensity were observed in the yoga group when compared to the control group at 24 weeks . A significantly greater proportion of yoga subjects also reported clinical improvements at both 12 and 24 weeks . In addition , depression was significantly lower in yoga subjects . Furthermore , while a reduction in pain medication occurred , this was comparable in both groups . When results were analyzed using per- protocol analysis , improvements were observed for all outcomes in the yoga group , including agreater trend for reduced pain medication usage . Although slightly less than at 24 weeks , the yoga group had statistically significant reductions in functional disability , pain intensity , and depression compared to st and ard medical care 6-months postintervention . Conclusion . Yoga improves functional disability , pain intensity , and depression in adults with CLBP . There was also a clinical ly important trend for the yoga group to reduce their pain medication usage compared to the control group |
12,450 | 26,202,783 | Authors ' conclusions Treating children known to have worm infection may have some nutritional benefits for the individual .
However , in mass treatment of all children in endemic areas , there is now substantial evidence that this does not improve average nutritional status , haemoglobin , cognition , school performance , or survival | Background The World Health Organization ( WHO ) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common .
As the intervention is often cl aim ed to have important health , nutrition , and societal effects beyond the removal of worms , we critically evaluated the evidence on benefits .
Objectives To summarize the effects of giving deworming drugs to children to treat soil‐transmitted helminths on weight , haemoglobin , and cognition ; and the evidence of impact on physical well‐being , school attendance , school performance , and mortality . | Background More than a third of the world 's children are infected with intestinal nematodes . Current control approaches emphasise treatment of school age children , and there is a lack of information on the effects of deworming preschool children . Methodology We studied the effects on the heights and weights of 3,935 children , initially 1 to 5 years of age , of five rounds of anthelmintic treatment ( 400 mg albendazole ) administered every 6 months over 2 years . The children lived in 50 areas , each defined by precise government boundaries as urban slums , in Lucknow , North India . All children were offered vitamin A every 6 months , and children in 25 r and omly assigned slum areas also received 6-monthly albendazole . Treatments were delivered by the State Integrated Child Development Scheme ( ICDS ) , and height and weight were monitored at baseline and every 6 months for 24 months ( trial registration number NCT00396500 ) . p Value calculations are based only on the 50 area-specific mean values , as r and omization was by area . Findings The ICDS infrastructure proved able to deliver the interventions . 95 % ( 3,712/3,912 ) of those alive at the end of the study had received all five interventions and had been measured during all four follow-up surveys , and 99 % ( 3,855/3,912 ) were measured at the last of these surveys . At this final follow up , the albendazole-treated arm exhibited a similar height gain but a 35 ( SE 5 ) % greater weight gain , equivalent to an extra 1 ( SE 0.15 ) kg over 2 years ( 99 % CI 0.6–1.4 kg , p = 10−11 ) . Conclusions In such urban slums in the 1990s , five 6-monthly rounds of single dose anthelmintic treatment of malnourished , poor children initially aged 1–5 years results in substantial weight gain . The ICDS system could provide a sustainable , inexpensive approach to the delivery of anthelmintics or micronutrient supplements to such population s. As , however , we do not know the control parasite burden , these results are difficult to generalize . Trial Registration Clinical Trials.gov Background Helminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially . We evaluated the effects of albendazole treatment , every three months for 21 months , on STH , malarial parasitemia and allergy . Methods and Findings A household-based cluster-r and omized , double-blind , placebo-controlled trial was conducted in an area in Indonesia endemic for STH . Using computer-aided block r and omization , 481 households ( 2022 subjects ) and 473 households ( 1982 subjects ) were assigned to receive placebo and albendazole , respectively , every three months . The treatment code was concealed from trial investigators and participants . Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test ( SPT ) to allergens as well as reported symptoms of allergy in children aged 5–15 years . The general impact of treatment on STH prevalence and body mass index ( BMI ) was evaluated . Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen . Analysis was by intention to treat . At 9 and 21 months post-treatment 80.8 % and 80.1 % of the study subjects were retained , respectively . The intensive treatment regiment result ed in a reduction in the prevalence of STH by 48 % in albendazole and 9 % in placebo group . Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment ( OR 4.16(1.35–12.80 ) ) and no statistically significant increase in SPT reactivity ( OR 1.18(0.74–1.86 ) at 9 months or 1.37 ( 0.93–2.01 ) 21 months ) . No effect of anthelminthic treatment was found on BMI , reported malaria-like- and allergy symptoms . No adverse effects were reported . Conclusions The study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH . This degree of reduction appears safe without any increased risk of malaria or allergies . Trial Registration Controlled-Trials.com IS RCT Background Tribendimidine is an anthelminthic drug with a broad spectrum of activity . In 2004 the drug was approved by Chinese authorities for human use . The efficacy of tribendimidine against soil-transmitted helminths ( Ascaris lumbricoides , hookworm , and Trichuris trichiura ) has been established , and new laboratory investigations point to activity against cestodes and Strongyloides ratti . Methodology /Principal Findings In an open-label r and omized trial , the safety and efficacy of a single oral dose of albendazole or tribendimidine ( both drugs administered at 200 mg for 5- to 14-year-old children , and 400 mg for individuals ≥15 years ) against soil-transmitted helminths , Strongyloides stercoralis , and Taenia spp . were assessed in a village in Yunnan province , People 's Republic of China . The analysis was on a per- protocol basis and the trial is registered with controlled-trials.com ( number IS RCT N01779485 ) . Both albendazole and tribendimidine were highly efficacious against A. lumbricoides and , moderately , against hookworm . The efficacy against T. trichiura was low . Among 57 individuals who received tribendimidine , the prevalence of S. stercoralis was reduced from 19.3 % to 8.8 % ( observed cure rate 54.5 % , p = 0.107 ) , and that of Taenia spp . from 26.3 % to 8.8 % ( observed cure rate 66.7 % , p = 0.014 ) . Similar prevalence reductions were noted among the 66 albendazole recipients . Taking into account “ new ” infections discovered at treatment evaluation , which were most likely missed pre-treatment due to the lack of sensitivity of available diagnostic approaches , the difference between the drug-specific net Taenia spp . cure rates was highly significant in favor of tribendimidine ( p = 0.001 ) . No significant adverse events of either drug were observed . Conclusions / Significance Our results suggest that single-dose oral tribendimidine can be employed in setting s with extensive intestinal polyparasitism , and its efficacy against A. lumbricoides and hookworm was confirmed . The promising results obtained with tribendimidine against S. stercoralis and Taenia spp . warrant further investigations . In a next step , multiple-dose schedules should be evaluated Background There is considerable debate on the health impacts of soil-transmitted helminth infections . We assessed effects of deworming on physical fitness and strength of children in an area in Yunnan , People 's Republic of China , where soil-transmitted helminthiasis is highly endemic . Methodology The double-blind , r and omized , placebo-controlled trial was conducted between October 2011 and May 2012 . Children , aged 9–12 years , were treated with either triple-dose albendazole or placebo , and monitored for 6 months post-treatment . The Kato-Katz and Baermann techniques were used for the diagnosis of soil-transmitted helminth infections . Physical fitness was assessed with a 20-m shuttle run test , where the maximum aerobic capacity within 1 min of exhaustive exercise ( VO2 max estimate ) and the number of 20-m laps completed were recorded . Physical strength was determined with grip strength and st and ing broad jump tests . Body height and weight , the sum of skinfolds , and hemoglobin levels were recorded as secondary outcomes . Principal Findings Children receiving triple-dose albendazole scored slightly higher in the primary and secondary outcomes than placebo recipients , but the difference lacked statistical significance . Trichuris trichiura-infected children had 1.6 ml kg−1 min−1 ( P = 0.02 ) less increase in their VO2 max estimate and completed 4.6 ( P = 0.04 ) fewer 20-m laps than at baseline compared to non-infected peers . Similar trends were detected in the VO2 max estimate and grip strength of children infected with hookworm and Ascaris lumbricoides , respectively . In addition , the increase in the VO2 max estimate from baseline was consistently higher in children with low-intensity T. trichiura and hookworm infections than in their peers with high-intensity infections of all soil-transmitted helminths ( range : 1.9–2.1 ml kg−1 min−1 ; all P<0.05 ) . Conclusions / Significance We found no strong evidence for significant improvements in physical fitness and anthropometric indicators due to deworming over a 6-month follow-up period . However , the negative effect of T. trichiura infections on physical fitness warrants further investigation The prevalence rate of ascariasis in primary school children in northern Jakarta , Indonesia varies from 60 % to 90 % . An association between helminthic infection and educational achievement has long been recognized . This study was carried out in the northern part of Jakarta among primary school children 6 - 8 years of age . Treatment of ascariasis and health education were used as the interventions . Before the interventions , basic data on socioeconomic status , epidemiology , infection with Ascaris lumbricoides , nutritional status , and cognitive function were collected . After the interventions , only data on infection with A. lumbricoides , nutritional status , and cognitive function were collected . The children were divided into five groups . Group I was given an anthelminthic ( mebendazole ) , group II was provided with health education , group III was given an antihelminthic and provided with health education , group IV was given a placebo ( controls ) , and group V consisted of egg-negative children , who also served as controls . Data from 336 students were analyzed by analysis of covariance . Parasitologic examinations showed a mean prevalence rate of 58.4 % for A. lumbricoides infection in the pre-intervention children and a mean prevalence rate of 40.6 % in the post-intervention children . Concerning nutritional status , approximately 80 % of the children showed good scores in the pre- and post-treatment data , and only a small percentage ( 0.9 - 16.2 % ) showed mild or moderate malnutrition . No significant difference was found between the pre- and post-treatment nutritional status . The results of the cognitive test showed that the group treated with mebendazole showed significant improvement in the Colored Progressive Matrices and Coding test . Children also showed an improvement in their learning ability , concentration , and eye-h and coordination after five months of receiving this intervention BACKGROUND The effect of helminth infestation on the nutrition , growth , and physiology of the host is still poorly understood . Anthelmintic treatment of children in developing countries has had varying success in terms of growth improvements . OBJECTIVE The objective of this study was to assess the effect of regular deworming on child growth , physiology , and biochemical status . DESIGN The study was a 12-mo longitudinal intervention in 123 Bangladeshi children aged 2 - 5 y. Treatment ( mebendazole ) or placebo tablets were administered every 2 mo for 8 mo and again at 12 mo . Weight , height , midupper arm circumference , intestinal permeability , plasma albumin , alpha(1)-antichymotrypsin , and total protein concentration were assessed every 2 mo . RESULTS Treatment with mebendazole reduced the prevalence of Ascaris lumbricoides from 78 % to 8 % , of Trichuris trichiura from 65 % to 9 % , and of hookworm from 4 % to 0 % . There was no significant difference in the growth of treated children compared with those given placebo tablets . No changes in intestinal permeability or plasma albumin were observed after deworming . Significant decreases in total protein ( P<0.001 ) and alpha(1)-antichymotrypsin ( P<0.001 ) were observed in the treatment group , indicating possible reductions in inflammation and immunoglobulin concentration after deworming . A significant increase in the prevalence of Giardia intestinalis ( from 4 % to 49 % ) in the treatment group was associated with a short-term reduction in weight ( P = 0.02 ) and higher intestinal permeability ( P < 0.001 ) in infected subjects . No long-term effects of G. intestinalis on growth were observed . CONCLUSION Low-intensity helminth infections , predominantly of A. lumbricoides and T. trichiura , do not contribute significantly to the poor growth and biochemical status of rural Bangladeshi children We studied growth in infected children given one dose ( 600 mg ) or two doses of albendazole per school year . Children were examined and allocated at r and om within sex by descending hookworm egg count to one of three groups : placebo ( n = 93 ) , one dose ( 1x , n = 96 ) or two doses ( 2x , n = 95 ) . Each child was treated and then re-examined and treated 3.6 and 8.2 mo later ( Exams 2 and 3 ) . The 1x and 2x groups gained significantly more by Exam 3 than the placebo group in weight ( 1.1 and 0.9 kg more , respectively ) , percent weight-for-age ( 3.3 and 2.7 percentage points more ) , percent weight-for-height ( 3.1 and 2.9 percentage points more ) , percent arm circumference-for-age ( 2.3 and 2.0 percentage points more ) and triceps and subscapular skinfolds but did not differ significantly from each other . The placebo group showed significant decreases between exams ( P < 0.0002 ) in percent weight-for-age and percent arm circumference-for-age and no change in percent weight-for-height , whereas the 1x and 2x groups exhibited significant increases ( P < 0.005 ) . At Exam 3 , arithmetic mean egg reduction rates for the 1x and 2x groups were 84 and 95 % for hookworm , 42 and 32 % for Trichuris and 55 and 87 % for Ascaris , respectively . We conclude that one or two doses of albendazole per year result ed in similar growth improvements , despite reinfection , in school-age children in an area where these helminths and poor growth are prevalent We studied physical fitness with the Harvard Step Test , growth , and appetite in primary school boys infected with hookworm ( 96 % baseline prevalence ) , Trichuris trichiura ( 98 % prevalence ) and Ascaris lumbricoides ( 41 % prevalence ) who received a single 600-mg dose of albendazole or an identical placebo . Boys were examined , allocated at r and om within pairs by descending hookworm egg count to placebo ( n = 26 ) or albendazole ( n = 27 ) groups , treated , and re-examined 4 mo later . Four months after treatment , the albendazole group showed highly significant improvements in fitness score , resting heart rate , and heart rates at 1 , 2 , 3 and 4 min after the Harvard Step Test , whereas the placebo group had not changed significantly . The albendazole group also exhibited significantly more rapid growth judged by weight gain ( 1.0 kg greater than the placebo group , P < 0.0002 ) , height increment ( 0.6 cm more , P < 0.003 ) , arm circumference ( 0.3 cm more , P < 0.0002 ) , and triceps and subscapular skinfolds ( 1.0 mm more , P < 0.0002 ) , and showed improved appetite with objective and subjective measures . We conclude that single-dose treatment with albendazole can allow improved physical fitness , growth , and appetite in school-age children in areas where these helminths and poor growth are highly prevalent In developing countries , both marginal vitamin A status and intestinal helminths are common among children . Indonesian children ( n = 309 , 0.6 - 6.6 y ) , known to be infected with Ascaris lumbricoides , were r and omized into six different treatment groups ( A-F ) . The treatments included 210 mumol vitamin A supplement and a dose of 400 mg albendazole ( 5-propylthio-1H-benzimidazol-2-yl carbamic acid methyl ester ) administered orally either at the same health visit ( Groups B and F ) or at different contact times during a 1-mo period ( groups A , C , D and E ) . Vitamin A status was assessed both before and 3 - 4 wk after the treatments by the modified relative dose response ( MRDR ) test . Vitamin A supplementation was most important in improving the vitamin A status ( P < 0.0001 ) of these children , whereas treatment for ascariasis alone ( P = 0.370 ) and the statistical interaction between treatment for ascariasis and vitamin A ( P = 0.752 ) were not . Serum retinol concentrations marginally improved ( P = 0.051 ) in two of the groups that received vitamin A and albendazole but not in the third group that received vitamin A only . The MRDR test proved a better discriminator of the effects of these treatments on vitamin A status than changes in serum retinol concentrations A r and omized controlled trial was conducted in eastern Zaire to assess the effects of high dose vitamin A supplementation and regular deparasitation on the growth of 358 moderately malnourished preschool children , discharged from the hospital . The treatment groups received either vitamin A ( 60 mg of oily solution of retinyl palmitate , 30 mg if aged < 12 mo ) every 6 mo or mebendazole ( 500 mg ) every 3 mo ; the control group received no supplementation . Anthropometric data were gathered at baseline and after 6 and 12 mo of follow-up . Serum retinol concentrations were measured at baseline and after 3 mo . The three groups did not differ in sociodemographic indicators , age and sex composition , nutritional status and serum retinol concentrations at baseline . In children who were vitamin A deficient at baseline , adjusted mean weight and mid-upper arm circumference ( MUAC ) increments were higher in the vitamin A-supplemented group than in the control group [ annual increment in weight and MUAC in vitamin A vs. control group : 2.088 vs. 1.179 kg ( P = 0.029 ) and 2.24 vs. 0.95 cm ( P = 0.012 ) , respectively ] , whereas growth increment did not differ between the dewormed group and the control group . In children who were not vitamin A deficient at baseline , growth increment did not differ between the vitamin A-supplemented and control groups , whereas weight gain was lower in the dewormed group than in the control group . Vitamin A-supplemented boys gained more weight and height than control boys , whereas vitamin A-supplemented girls gained less height than control girls . Dewormed boys and girls gained less weight than control boys and girls . Programs to improve vitamin A status by high dose vitamin A supplementation may improve growth of preschool children who are vitamin A deficient , whereas deworming does not Efficacy trials of antihelminthic therapies conducted in Africa have reported improvements in children 's growth , but nutritional evaluations of large-scale deworming programs are lacking . We evaluated the first-year effect on growth of a school-based deworming program in Zanzibar , where growth retardation occurs in school children . Children in four primary schools were given thrice-yearly mebendazole ( 500 mg ) and compared with children in four schools that received twice-yearly mebendazole and children in four non-program schools . Evaluation schools were r and omly selected and allocated to control , twice-yearly or thrice-yearly deworming . Approximately 1000 children in each program group completed the 1-y follow-up . Children < 10 y old gained 0.27 kg more weight ( P < 0.05 ) and 0.13 cm more height ( P = 0.20 ) in the twice-yearly group , and 0 . 20 kg more weight ( P = 0.07 ) and 0.30 cm more height ( P < 0.01 ) in the thrice-yearly group , compared with the control group . Children < 10 y old with higher heights-for-age at baseline had higher weight and height gains in response to deworming . In children > /=10 y old , overall program effects on height or weight gains were not significant . But in this age range , younger boys had significant improvements in height gain with thrice-yearly deworming , and children with higher heights-for-age had greater improvements in weight gain with deworming . We conclude that the deworming program improved the growth of school children , especially children who were younger and less stunted , but the improvements were small . More effective antihelminthic regimens or additional dietary or disease control interventions may be needed to substantially improve the growth of school children in areas such as Zanzibar We evaluated the effects of the Zanzibar school-based deworming program on the iron status of primary school children . Parasitologic and nutritional assessment s were carried out at baseline , 6 mo , and 12 mo in 4 nonprogram schools ( n = 1002 ) , 4 schools in which students received twice-yearly deworming ( n = 952 ) , and 4 schools in which students received thrice-yearly deworming ( n = 970 ) with 500 mg generic mebendazole . Schools were r and omly selected for evaluation and allocated to program groups . Relative to no treatment , thrice-yearly deworming caused significant decreases in protoporphyrin concentrations and both deworming regimens caused marginally significant increases in serum ferritin concentrations . The average annual changes in protoporphyrin concentrations were -5.9 and -23.5 micromol/mol heme in the control and thrice-yearly deworming groups , respectively ( P < 0.001 ) . The average changes in ferritin concentration were 2.8 and 4.5 microg/L , respectively ( P = 0.07 ) . Deworming had no effect on annual hemoglobin change or prevalence of anemia . However , the relative risk of severe anemia ( hemoglobin < 70 g/L ) was 0.77 ( 95 % confidence limits : 0.39 , 1.51 ) in the twice-yearly deworming group and 0.45 ( 0.19 , 1.08 ) in the thrice-yearly deworming group . The effects on prevalence of high protoporphyrin values and incidence of moderate-to-severe anemia ( hemoglobin < 90 g/L ) were significantly greater in children with > 2000 hookworm eggs/g feces at baseline . We estimate that this deworming program prevented 1260 cases of moderate-to-severe anemia and 276 cases of severe anemia in a population of 30,000 schoolchildren in 1 y. Where hookworm is heavily endemic , deworming programs can improve iron status and prevent moderate and severe anemia , but deworming may be needed at least twice yearly Iron deficiency and helminth infections are two common conditions of children in developing countries . The consequences of helminth infection in young children are not well described , and the efficacy of low dose iron supplementation is not well documented in malaria-endemic setting s. A 12-mo r and omized , placebo controlled , double-blind trial of 10 mg daily iron and /or mebendazole ( 500 mg ) every 3 mo was conducted in a community-based sample of 459 Zanzibari children age 6 - 71 mo with hemoglobin > 70 g/L at baseline . The trial was design ed to examine treatment effects on growth , anemia and appetite in two age subgroups . Iron did not affect growth retardation , hemoglobin concentration or mild or moderate anemia ( hemoglobin < 110 g/L or < 90 g/L , respectively ) , but iron significantly improved serum ferritin and erythrocyte protoporphyrin . Mebendazole significantly reduced wasting malnutrition . but only in children < 30 mo old . The adjusted odds ratios ( AORs ) for mebendazole in this age group were 0.38 ( 95 % CI : 0.16 , 0.90 ) for weight-for-height less than -1 Z-score and 0.29 ( 0.09 , 0.91 ) for small arm circumference . In children < 24 mo old , mebendazole also reduced moderate anemia ( AOR : 0.41 , 0.18 , 0.94 ) . Both iron and mebendazole improved children 's appetite , according to mothers ' report . In this study , iron 's effect on anemia was limited , likely constrained by infection , inflammation and perhaps other nutrient deficiencies . Mebendazole treatment caused unexpected and significant reductions in wasting malnutrition and anemia in very young children with light infections . We hypothesize that incident helminth infections may stimulate inflammatory immune responses in young children , with deleterious effects on protein metabolism and erythropoiesis One-hundred eighty-five Bangladeshi children age 1 1/2 to 8 yr with no Ascaris lumbricoides infection or with light , moderate , or heavy infection were r and omly assigned to treatment of placebo groups , with treatment given in a double-blind fashion . The groups were comparable for nutritional and socioeconomic parameters . Treatment consisted of a single dose of piperazine citrate administered twice within a 2-wk period . The cure rates for the low , moderate , and heavy A. lumbricoides infected subgroups were 53 , 31 , and 36 % , respectively . With more severe infections , worm eradication was more difficult and the rate of reinfection after treatment was more rapid . The rate of reinfection was significantly different for the low A. lumbricoides infected treatment and placebo subgroups for 5 months after treatment , for the moderate treatment and placebo subgroups for 3 months after treatment , and for the heavy A. lumbricoides infected treatment and placebo subgroups there was a difference , although not significant , for 1 month after treatment . Anthropometric measurements were obtained for a period of 11 months . Analysis of covariance revealed no significant difference for change of weight , change of height , weight-for age , weight-for-height , height-for-age , triceps skinfold , midarm circumference , and the abdominal girth to chest circumference ratio between the treatment and placebo groups after drug administration . The results of this study do not support single dose worm therapy as a means to enhance growth The provision of vitamin A in food sources of beta-carotene is an alternative to the distribution of high-dose capsules . To examine factors that may influence the success of food-based programs , a study was carried out in Sumatra , Indonesia , of the effect of food sources of beta-carotene , extra dietary fat , and Ascaris lumbricoides infection on serum retinol concentrations in children . Meals and snacks with various amounts of beta-carotene and fat were fed at midday to children 3 - 6 y of age for 3 wk . Some groups of children were dewormed with the anthelmintic levamisole before the feeding period , whereas others remained infected . Results showed that the incorporation of beta-carotene sources ( mainly in the form of red sweet potatoes ) into the meal significantly increased serum retinol concentrations . The greatest rise in serum retinol occurred when meals contained added beta-carotene sources and added fat and the children were dewormed . Adding more fat to the meal and deworming the children caused a rise in serum retinol similar to that seen when feeding additional beta-carotene sources . Moreover , the effects of fat and deworming together were additive to the effects of additional beta-carotene sources . When the meal contained additional beta-carotene sources , added fat caused a further improvement in serum retinol concentrations but only if A. lumbricoides infection was low . These studies indicated that food-based interventions in vitamin A-deficient areas might be successful and that other interventions such as increasing dietary fat concentrations and anthelmintic treatment should be considered along with increasing consumption of beta-carotene-rich food The effect of weekly iron supplementation with and without deworming on hemoglobin was investigated in a double-masked , placebo-controlled field trial . Subjects were 289 preschoolers who were r and omly divided into three groups . Groups 1 and 2 received 30 mg Fe once weekly and group 3 received a placebo . Group 1 additionally received anthelminthic treatment . Supplements were administered by the mothers , who were educated about iron deficiency beforeh and . In the iron-supplemented groups prevalence of anemia decreased from 37.2 % to 16.2 % ( P < 0.001 ) . Hemoglobin increased by an average of 6.9 + /- 9.8 g/L in the two iron-supplemented groups ( n = 191 ) , which was greater ( P < 0.001 ) than the increase of 1.9 + /- 8.0 g/L in the placebo group . None of the subjects had hookworm , and anthelminthic treatment did not have an additional effect . Iron supplements administered once weekly by mothers reduced anemia without major involvement of health staff Growth , activity , appetite and intestinal helminth infections were compared for 55 Kenyan primary school children with hookworm ( 93 % prevalence ) , T. trichiura ( 84 % prevalence ) and A. lumbricoides ( 29 % prevalence ) before and 9 wk after treatment with three 400-mg doses of albendazole ( Zentel ) or placebo . Fecal sample s were examined for helminth eggs using a modified Kato technique . Activity was measured during free-play with motion recorders on the dominant thigh . Children rated their appetites on a 5-point scale . After baseline measurements , children were r and omly allocated to the albendazole-treated ( n = 28 ) and placebo ( n = 27 ) groups , treated , and re-examined 9 wk later . At follow-up , egg counts were significantly lower than at baseline in the albendazole-treated group ( P < or = 0.002 ) , and gains in activity , reported appetite and most indices of growth were significantly greater for the albendazole-treated group than for the placebo group . We conclude that treatment of undernourished school children for intestinal helminth infections with albendazole may improve growth and appetite and increase spontaneous physical activity One hundred fifty-nine children aged 24 to 61 months with 60 % ascariasis prevalence and 21.5 % giardiasis prevalence in rural Guatemala were studied prospect ively for 1 yr . They were divided into four groups comparable for age , sex , socioeconomic status , and past growth experience as judged by slopes of height and weight on age . Each group was r and omly assigned to the following 2-monthly treatment regimens : group I , placebo , group II , piperazine , group III , metronidazole ; group IV , piperazine and metronidazole . Height and weight were measured every 3 months and stools were examined for parasites every 4 months . Piperazine administration decreased the prevalence of ascariasis to 33.8 % at the end of the study but growth remained unaltered . Metronidazole administration decreased the prevalence of giardiasis to 2.5 % at the end of the study and was accompanied by increased growth as judged by delta weight , delta % weight for age , slope of weight on age , delta height , delta % height for age and slope of height on age . It is suggested that failure of antiascaris treatment to enhance growth in this study may be because of 1 ) absence of severe malnutrition in the subjects , 2 ) adequacy of dietary protein , 3 ) possible low worm load , and 4 ) failure to eradicate ascariasis . The findings suggest that giardiasis is associated with reduced growth in preschool children The effects of treating Trichuris trichiura infections were investigated in 407 Jamaican children age 6 to 12 y. The children were r and omly assigned to receive treatment ( albendazole ) or a placebo . The outcome variables included growth , tests of reading , spelling and arithmetic , and school attendance . After 6 mo of treatment , there was no significant main effect on any of the outcomes . However , there were significant treatment-by-infection intensity interactions with spelling ( P < 0.05 ) and body mass index ( P < 0.01 ) , and a significant treatment-by-stunting interaction with school attendance ( P < 0.01 ) . In spelling , the children with heavy infections showed improvements with treatment that approached significance ( P = 0.06 ) , whereas those with lower intensities did not . However , the children with lower infection intensities had increased body mass index with treatment ( P = 0.02 ) , although there was no difference in children with heavy infections . In school attendance , the stunted children improved with treatment ( P < 0.04 ) , whereas there was no difference in the nonstunted children . These findings suggest that in the sample of Jamaican children examined , the treatment of T. trichiura was more likely to benefit school performance in children of poor nutritional status and those with heavy infections , and to improve weight gain in children with lighter infection intensities A double-blind placebo trial was conducted to determine the effect of moderate to high loads of Trichuris trichiura ( whipworm ) infection on the cognitive functions of 159 school children ( age 9 - 12 years ) in Jamaica . Infected children were r and omly assigned to Treatment or Placebo groups . A third group of r and omly selected uninfected children were assigned to a Control for comparative purpose s. The improvement in cognitive function was evaluated using a stepwise multiple linear regression , design ed to control for any confounding variables . The expulsion of worms led to a significant improvement in tests of auditory short-term memory ( P less than 0.02 ; P less than 0.01 ) , and a highly significant improvement in the scanning and retrieval of long-term memory ( P less than 0.001 ) . After 9 weeks , treated children were no longer significantly different from an uninfected Control group in these three tests of cognitive function . The removal of T. trichiura was more important than Ascaris lumbricoides in determining this improvement . The results suggest that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy In order to test the impact of Giardia and geohelminthic infection on infant growth faltering in Bangladesh , a r and omised double-blind placebo controlled intervention of 36 weeks ' duration was conducted in a rural community located 40 km northwest of Dhaka . Infants aged between 3 and 15 months were r and omly assigned to either anti-Giardia and anthelminthic treatment , anti-Giardia treatment only , or a control . Weight and supine length were recorded every 4 weeks . Every 12 weeks intestinal permeability ( lactulose/mannitol ratio ) , haemoglobin , plasma albumin , alpha-1-acid glycoprotein , IgG and Giardia-specific IgM ( GSIgM ) and eggs of the three common geohelminths and G. intestinalis cysts were determined . Data on 222 fully compliant infants were analysed . No significant differences in intestinal permeability , biochemical or anthropometric variables were found between the intervention groups , although there were associations between improvement in small intestinal mucosal function and better weight-for-age and weight-for-height ( length ) Z-scores . GSIgM titres indicated high endemicity with rapid re-infection of Giardia among infants ; over 95 % of infants were positive throughout the study , whereas the stool examination showed very few infants with either geohelminth eggs or Giardia cysts Background Helminths have profound effects on the immune response , allowing long-term survival of parasites with minimal damage to the host . Some of these effects “ spill-over ” , altering responses to non-helminth antigens or allergens . It is suggested that this may lead to impaired responses to immunizations and infections , while conferring benefits against inflammatory responses in allergic and autoimmune disease . These effects might develop in utero , through exposure to maternal helminth infections , or through direct exposure in later life . Purpose To determine the effects of helminths and their treatment in pregnancy and in young children on immunological and disease outcomes in childhood . Methods The trial has three r and omized , double-blind , placebo-controlled interventions at two times , in two people : a pregnant woman and her child . Pregnant women are r and omized to albendazole or placebo and praziquantel or placebo . At age 15 months their children are r and omized to three-monthly albendazole or placebo , to continue to age five years . The proposed design ation for this sequence of interventions is a 2 × 2( × 2 ) factorial design . Children are immunized with BCG and against polio , Diphtheria , tetanus , Pertussis , Haemophilus , hepatitis B and measles . Primary immunological outcomes are responses to BCG antigens and tetanus toxoid in whole blood cytokine assays and antibody assays at one , three and five years of age . Primary disease outcomes are incidence of malaria , pneumonia , diarrhoea , tuberculosis , measles , vertical HIV transmission , and atopic disease episodes , measured at clinic visits and twice-monthly home visits . Effects on anaemia , growth and intellectual development are also assessed . Conclusion This trial , with a novel design comprising related interventions in pregnant women and their offspring , is the first to examine effects of helminths and their treatment in pregnancy and early childhood on immunological , infectious disease and allergic disease outcomes . The results will enhance underst and ing of both detrimental and beneficial effects of helminth infection and inform policy Introduction : Helminth ( worm ) infections cause morbidity among poor communities worldwide . An influential study conducted in Kenya in 1998–99 reported that a school-based drug- and -educational intervention had benefits for worm infections and school attendance . Methods : In this statistical replication , we re-analysed data from this cluster quasi-r and omized stepped-wedge trial , specifying two co- primary outcomes : school attendance and examination performance . We estimated intention-to-treat effects using year-stratified cluster- summary analysis and observation-level r and om-effects regression , and combined both years with a r and om-effects model accounting for year . The participants were not blinded to allocation status , and other interventions were concurrently conducted in a sub-set of schools . A protocol guiding outcome data collection was not available . Results : Quasi-r and omization result ed in three similar groups of 25 schools . There was a substantial amount of missing data . In year-stratified cluster- summary analysis , there was no clear evidence for improvement in either school attendance or examination performance . In year-stratified regression models , there was some evidence of improvement in school attendance [ adjusted odds ratios ( aOR ) : year 1 : 1.48 , 95 % confidence interval ( CI ) 0.88–2.52 , P = 0.147 ; year 2 : 1.23 , 95 % CI 1.01–1.51 , P = 0.044 ] , but not examination performance ( adjusted differences : year 1 : −0.135 , 95 % CI −0.323–0.054 , P = 0.161 ; year 2 : −0.017 , 95 % CI −0.201–0.166 , P = 0.854 ) . When both years were combined , there was strong evidence of an effect on attendance ( aOR 1.82 , 95 % CI 1.74–1.91 , P < 0.001 ) , but not examination performance ( adjusted difference −0.121 , 95 % CI −0.293–0.052 , P = 0.169 ) . Conclusions : The evidence supporting an improvement in school attendance differed by analysis method . This , and various other important limitations of the data , caution against over-interpretation of the results . We find that the study provides some evidence , but with high risk of bias , that a school-based drug-treatment and health-education intervention improved school attendance and no evidence of effect on examination performance Objective : To assess the effects of iron and deworming on linear growth performance of preschoolers . Design : Three-month r and omized , double-blind and placebo-controlled trial . The children were allocated to four treatments : iron ( 60 mg elemental iron/day)+albendazole ( 200 mg/day for 3 consecutive days , repeated 1 month later ) , iron+albendazole-placebo , albendazole+iron-placebo or placebos . The supplementation was supervised . Subjects : A group of 177 children aged 3–5 y was selected from low-income households in a rural area in southern Bénin . A complete data set was analysed for 140 subjects . Many children were stunted ( 58 % had height-for-age Z-score < −2 ) , none were wasted ( 2 % had weight-for-height Z-score < −2 ) and 76 % were anemic ( Hb<110 g/l).Main outcome measures : Anthropometric parameters , hemoglobin and eggs per gram feces . Results : No significant difference in changes in anthropometric parameters was observed between study groups , and also not in a sub- sample of stunted and anemic subjects . Changes in hemoglobin were highest in the iron-treated subjects at the end of the 3-month intervention period ( P=0.032 ) . The difference between the iron and the placebo groups remained significant even 7 months later ( P=0.022 ) . The difference was 5 g/l in both periods . Ascaris lumbricoides and hookworm infections decreased significantly in albendazole-treated subjects ( P<0.05 ) . Conclusions : In addition to recurrent parasitic infection burden , the children may have multiple micronutrient deficiencies . Therefore , it may be interesting to study appetite and food intake of young toddlers in relation to health and linear growth performance in poor environments . Sponsorship : The Nestlé Foundation ( Lausanne , Switzerl and ) .European Journal of Clinical Nutrition ( 2001 ) 55 , Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more We conducted a r and omized clinical intervention trial over 24 weeks on a tea estate in north-east Bangladesh to investigate the effect of iron supplementation and anthelmintic treatment on the labour productivity of adult female tea pluckers . A total of 553 full-time tea pluckers , not pregnant and not breastfeeding , were r and omly assigned to one of the four intervention groups : group 1 received iron supplementation on a weekly basis , group 2 received anthelmintic treatment at the beginning and half-way through the trial ( week 12 ) , group 3 received both iron supplementation as group 1 and anthelmintic treatment as group 2 , and group 4 was a control group and received placebos . No significant difference in labour productivity was found between the four intervention groups over the trial period . However , there was a negative association for all three worms ( Ascaris lumbricoides , Trichuris trichiura and hookworms ) between the intensity of helminth infections ( eggs/g faeces ) and all measures of labour productivity . Lower haemoglobin values and anaemia ( < 120 g/l Hb ) were both associated with lower labour productivity and more days sick and absent . Taller women with greater arm circumference were able to pluck more green leaves , earn higher wages and were absent less often Tested 47 first-year primary school children at a mission school in rural Zaire for cognitive ability with the Kaufman Assessment Battery for Children ( K-ABC ) adopted to the language of Kituba . Within a day of this test , each child was evaluated for blood hemoglobin ( Hgb ) level and the presence of intestinal parasites . Half of the children received an iron supplement ( 20 mg Fe ) for 30 days and those children positive for the intestinal parasites of ankylostome or ascaris were r and omly selected to receive either a vermifuge treatment or placebo . All of the children were again evaluated medically and cognitively 4 weeks after the initiation of treatment . Using discriminant analysis , performance on the Mental Processing Composite of the K-ABC 1 month after treatment in combination with increases in blood Hgb result ed in the successful classification of 74 % in terms whether a child had received both iron supplement and vermifuge treatment ( p = .007 ) . With respect to our home evaluation for each child , factors related to the nutritional and economic well-being of the home environment proved a reliable marker for Simultaneous Processing ability . However , the present findings also suggest that over the short-term , changes in blood Hgb that accompany both vermifuge and iron supplement treatment together can improve certain aspects of cognitive ability , perhaps by means of heightened attentional capacity This r and omized , placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths ( albendazole ) and lymphatic filariasis ( ivermectin ) . Children were infected with Ascaris ( 29.2 % ) , Trichuris ( 42.2 % ) , and hookworm ( 6.9 % ) , with 54.7 % of children having one or more of these parasites . Wuchereria bancrofti microfilaria were found in 13.3 % of the children . Children were r and omly assigned to treatment with placebo , albendazole , ivermectin , or combined therapy . Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone . Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone . Only combination therapy result ed in significantly greater gains in height ( hookworm-infected children ) or weight ( Trichuris-infected children ) compared with the placebo group . Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and result ed in nutritional benefits not found with either drug alone Background Helminth infections can alter susceptibility to malaria . Studies need to determine whether or not deworming programs can impact on Plasmodium infections in preschool children . Methods A double-blind placebo-controlled r and omised trial was conducted to investigate the impact of anthelmintic treatment on Plasmodium infection in children aged 12 - 59 months . Children were r and omly assigned to receive either albendazole or placebo every four months for 12 months with a follow-up at 14 months . Results 320 children ( out of 1228 , 26.1 % ) complied with all the follow-up assessment s. Plasmodium prevalence and mean Plasmodium parasite density was significantly higher in the treatment group ( 44.9 % and 2319 ± SE 511 ) compared to the placebo group ( 33.3 % and 1471 ± 341 ) at baseline . The odds of having Plasmodium infection increased over time for children in both the placebo and treatment groups , however this increase was significantly slower for children in the treatment group ( P = 0.002 ) . By month 14 , mean Plasmodium density had increased by 156 % in the placebo group and 98 % in the treatment group but the rate of change in Plasmodium density was not significantly different between the groups . The change from baseline in haemoglobin had a steeper increase among children in the treatment group when compared to the placebo group but this was not statistically significant . Conclusions Repeated four-monthly anthelminthic treatments for 14 months result ed in a significantly lower increase in the prevalence of Plasmodium infection in preschool children which coincided with a reduction in both the prevalence and intensity of A. lumbricoides infections . Trial Registration Current controlled trials IS RCT Summary Background In north India many pre-school children are underweight , many have intestinal worms , and 2–3 % die at ages 1·0–6·0 years . We used the state-wide Integrated Child Development Service ( ICDS ) infrastructure to help to assess any effects of regular deworming on mortality . Methods Participants in this cluster-r and omised study were children in catchment areas of 8338 ICDS-staffed village child-care centres ( under-5 population 1 million ) in 72 administrative blocks . Groups of four neighbouring blocks were cluster-r and omly allocated in Oxford between 6-monthly vitamin A ( retinol capsule of 200 000 IU retinyl acetate in oil , to be cut and dripped into the child 's mouth every 6 months ) , albendazole ( 400 mg tablet every 6 months ) , both , or neither ( open control ) . Analyses of albendazole effects are by block ( 36 vs 36 clusters ) . The study spanned 5 calendar years , with 11 6-monthly mass-treatment days for all children then aged 6–72 months . Annually , one centre per block was r and omly selected and visited by a study team 1–5 months after any trial deworming to sample faeces ( for presence of worm eggs , reliably assessed only after mid- study ) , weigh children , and interview caregivers . Separately , all 8338 centres were visited every 6 months to monitor pre-school deaths ( 100 000 visits , 25 000 deaths at age 1·0–6·0 years [ the primary outcome ] ) . This trial is registered at Clinical Trials.gov , NCT00222547 . Findings Estimated compliance with 6-monthly albendazole was 86 % . Among 2589 versus 2576 children surveyed during the second half of the study , nematode egg prevalence was 16 % versus 36 % , and most infection was light . After at least 2 years of treatment , weight at ages 3·0–6·0 years ( st and ardised to age 4·0 years , 50 % male ) was 12·72 kg albendazole versus 12·68 kg control ( difference 0·04 kg , 95 % CI −0·14 to 0·21 , p=0·66 ) . Comparing the 36 albendazole-allocated versus 36 control blocks in analyses of the primary outcome , deaths per child-care centre at ages 1·0–6·0 years during the 5-year study were 3·00 ( SE 0·07 ) albendazole versus 3·16 ( SE 0·09 ) control , difference 0·16 ( SE 0·11 , mortality ratio 0·95 , 95 % CI 0·89 to 1·02 , p=0·16 ) , suggesting absolute risks of dying between ages 1·0 and 6·0 years of roughly 2·5 % albendazole versus 2·6 % control . No specific cause of death was significantly affected . Interpretation Existing ICDS village staff can be organised to deliver simple pre-school interventions sustainably for many years at low cost , but regular deworming had little effect on mortality in this lightly infected pre-school population . Funding UK Medical Research Council , USAID , World Bank ( albendazole donated by GlaxoSmithKline ) Background Systematic review s represent one of the most important tools for knowledge translation but users often struggle with underst and ing and interpreting their results . GRADE Summary -of- Findings tables have been developed to display results of systematic review s in a concise and transparent manner . The current format of the Summary -of- Findings tables for presenting risks and quality of evidence improves underst and ing and assists users with finding key information from the systematic review . However , it has been suggested that additional methods to present risks and display results in the Summary -of- Findings tables are needed . Methods / Design We will conduct a non-inferiority parallel-armed r and omized controlled trial to determine whether an alternative format to present risks and display Summary -of- Findings tables is not inferior compared to the current st and ard format . We will measure participant underst and ing , accessibility of the information , satisfaction , and preference for both formats . We will invite systematic review users to participate ( that is clinicians , guideline developers , and research ers ) . The data collection process will be undertaken using the online ' Survey Monkey ' system . For the primary outcome underst and ing , non-inferiority of the alternative format ( Table A ) to the current st and ard format ( Table C ) of Summary -of- Findings tables will be cl aim ed if the upper limit of a 1-sided 95 % confidence interval ( for the difference of proportion of participants answering correctly a given question ) excluded a difference in favor of the current format of more than 10 % . Discussion This study represents an effort to provide systematic review ers with additional options to display review results using Summary -of- Findings tables . In this way , review authors will have a variety of methods to present risks and more flexibility to choose the most appropriate table features to display ( that is optional columns , risks expressions , complementary methods to display continuous outcomes , and so on).Trials registration NCT02022631 ( 21 December 2013 Abstract Objective : To measure the effects of iron supplementation and anthelmintic treatment on iron status , anaemia , growth , morbidity , and development of children aged 6–59 months . Design : Double blind , placebo controlled r and omised factorial trial of iron supplementation and anthelmintic treatment . Setting : Community in Pemba Isl and , Zanzibar . Participants : 614 preschool children aged 6–59 months . Main outcome measures : Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups . Results : Before intervention , anaemia was prevalent and severe , and geohelminth infections were prevalent and light — Plasmodium falciparum infection was nearly universal . Iron supplementation significantly improved iron status , but not haemoglobin status . Iron supplementation improved language development by 0.8 ( 95 % confidence interval 0.2 to 1.4 ) points on the 20 point scale . Iron supplementation also improved motor development , but this effect was modified by baseline haemoglobin concentrations ( P=0.015 for interaction term ) and was apparent only in children with baseline haemoglobin concentrations < 90 g/l . In children with a baseline haemoglobin concentration of 68 g/l ( one st and ard deviation below the mean value ) , iron treatment increased scores by 1.1 ( 0.1 to 2.1 ) points on the 18 point motor scale . Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura , but not by hookworms . Mebendazole increased development scores by 0.4 ( −0.3 to 1.1 ) points on the motor scale and 0.3 ( −0.3 to 0.9 ) points on the language scale . Conclusions : Iron supplementation improved motor and language development of preschool children in rural Africa . The effects of iron on motor development were limited to children with more severe anaemia ( baseline haemoglobin concentration < 90 g/l ) . Mebendazole had a positive effect on motor and language development , but this was not statistically significant . What is already known on this topic Iron is needed for development and functioning of the human brain Anaemic children show developmental delays , but it is not yet clear whether iron deficiency causes these deficits or whether iron supplementation can reverse them Helminth infections in schoolchildren are associated with cognitive deficits , but few studies have been made of helminth infection and early child development What this study adds Low doses of oral iron supplementation given daily improved language development in children aged 1–4 years in Zanzibar Iron supplementation improved motor development , but only in children with initial haemoglobin concentrations below 90 g/l The effects of routine anthelmintic treatment on motor and language milestones were positive , but non-significant , with our sample The association between helminth infection and cognitive and motor function was investigated in school-age children in Java , Indonesia . 432 children from 42 primary schools participated in the study . Children were stratified by age and sex into two age groups , 8 - 9 years and 11 - 13 years . Children infected with hookworm performed significantly worse than children without hookworm infection in 6 of the 14 cognitive or motor tests . After controlling for school ( as a r and om effect ) plus age , socio-economic status and parental education , sex , stunting ( height-for-age < - 2sd ) , body mass index , haemoglobin concentration and the presence of A. lumbricoides and T. trichiura infections , infection with hookworm explained significantly lower scores on tests of Fluency ( P < 0.01 ) , Digit-Span Forwards ( P < 0.01 ) , Number Choice ( P < 0.01 ) , Picture Search ( P < 0.03 ) , Stroop Colour Word ( P < 0.02 ) and Mazes ( P < 0.001 ) . In 4 of the 6-tests ( Fluency , Number Choice , Picture Search and Mazes ) , there was a significant interaction between hookworm infection and age ( P < 0.03 ) , indicating that the association between hookworm and lower test scores increased with age . No associations were observed between hookworm infection and scores in tests of Digit-Span Backwards , Corsi-Block , Stroop Colour , Stroop Interference , Free Recall , Verbal Analogies , Bead Threading or the Pegboard ( P > 0.05 ) . Tests associated with helminths represented various functions of working memory . No significant associations between helminth infection and motor function were observed that could not be explained by chance . The results suggest that hookworm infection can have a significant adverse effect on children 's working memory which may have consequences for a child 's reasoning ability and reading comprehension . Although the results are only associational , the fact that differences in cognition were observed at baseline imply that preventing infection with helminths in school-age children could be of benefit Background Helminth infections may modulate immune responses to unrelated pathogens and allergens ; these effects may commence prenatally . We addressed the hypothesis that anthelminthic treatment in pregnancy and early childhood would improve responses to immunisation and modulate disease incidence in early childhood with both beneficial and detrimental effects . Methods and Findings A r and omised , double-blind , placebo-controlled trial was conducted in Entebbe , Ug and a [ IS RCT N32849447 ] . In three independent r and omisations , 2507 pregnant women were allocated to receive single-dose albendazole or placebo , and praziquantel or placebo ; 2016 of their offspring were r and omised to receive quarterly single-dose albendazole or placebo from age 15 months to 5 years . Primary outcomes were post-immunisation recall responses to BCG and tetanus antigens , and incidence of malaria , diarrhoea , and pneumonia ; incidence of eczema was an important secondary outcome . Analysis was by intention-to-treat . Of 2345 live births , 1622 ( 69 % ) children remained in follow-up at age 5 years . 68 % of mothers at enrolment , and 11 % of five-year-olds , had helminth infections . Maternal hookworm and Schistosoma mansoni were effectively treated by albendazole and praziquantel , respectively ; and childhood hookworm and Ascaris by quarterly albendazole . Incidence rates of malaria , diarrhoea , pneumonia , and eczema were 34 , 65 , 10 and 5 per 100 py , respectively . Albendazole during pregnancy caused an increased rate of eczema in the children ( HR 1.58 ( 95 % CI 1.15–2.17 ) , p = 0.005 ) . Quarterly albendazole during childhood was associated with reduced incidence of clinical malaria ( HR 0.85 ( 95 % CI 0.73–0.98 ) , p = 0.03 ) . There were no consistent effects of the interventions on any other outcome . Conclusions Routine use of albendazole in pregnancy may not always be beneficial , even in tropical developing countries . By contrast , regular albendazole treatment in preschool children may have an additional benefit for malaria control where helminths and malaria are co-endemic . Given the low helminth prevalence in our children , the effect of albendazole on malaria is likely to be direct . Trial registration Current Controlled Trials IS RCT Objective : The study was conducted to assess the effectiveness of six monthly albendazole ( ABZ ) for improving the weight and height of preschool children when initia ted at 0.5–1 year of age in population s with a high transmission rate of intestinal roundworm , Ascaris lumbricoides . It was a cluster r and omized trial in the urban slums of Lucknow , North India . Methods : Control children received 2 ml ( 1 ml to infants ) of Vitamin A every six month whereas those in the ABZ areas received , in addition , 400 mg of ABZ suspension ( Zentel , SKB ) every six month . Sixty-three and sixty-one slum areas were r and omized to albendazole ( ABZ ) or to control groups , respectively . Children aged 0.5–1 year were recruited in April 1996 and followed up for 1.5 years . Of 1022 children recruited from control and 988 from ABZ areas , the loss to follow-up at 1.5 year was 15.6 % and 14.6 % respectively . Mean ( ±SE ) weight gain in Kg in control versus ABZ areas was 3.04 ( 0.03 ) versus 3.22 ( 0.03 ) , ( p=0.01 ) . Results : After controlling for the presence of weight-for age z-score < -2.00 at enrollment in the ordinary least square ’s regression model , the extra weight gain in 1.5 years in those who received ABZ plus vitamin A was 0.13 Kg ( 95 % Cl:0.004 to 0.26 Kg . , p value=0.043 ) when compared to those who received only vitamin A ; underweight children at enrollment benefiting more than the normal ones . Conclusion : It was concluded that there was an improvement in weight with six monthly ABZ over 1.5 years . However , a much larger trial would be needed to determine whether there is any net effect of improvement in weight on under five mortality rate Background Children aged between one and five years are particularly vulnerable to disease caused by soil-transmitted helminths ( STH ) . Periodic deworming has been shown to improve growth , micronutrient status ( iron and vitamin A ) , and motor and language development in preschool children and justifies the inclusion of this age group in deworming programmes . Our objectives were to describe the prevalence and intensity of STH infection and to investigate the effectiveness of repeated four-monthly albendazole treatments on STH infection in children aged one to four years . Methods The study was carried out in four semi-urban villages situated near Ile-Ife , Osun State , Nigeria . The study was a double-blind placebo-controlled r and omised trial . Children aged one to four years were r and omly assigned to receive either albendazole or placebo every four months for 12 months with a follow-up at 14 months . Results The results presented here revealed that 50 % of the preschool children in these semi-urban communities were infected by one or more helminths , the most prevalent STH being Ascaris lumbricoides ( 47.6 % ) . Our study demonstrated that repeated four-monthly anthelminthic treatments with albendazole were successful in reducing prevalence and intensity of A. lumbricoides infections . At the end of the follow-up period , 12 % and 43 % of the children were infected with A. lumbricoides and mean epg was 117 ( S.E. 50 ) and 1740 ( S.E. 291 ) in the treatment and placebo groups respectively compared to 45 % and 45 % of the children being infected with Ascaris and mean epg being 1095 ( S.E. 237 ) and 1126 ( S.E. 182 ) in the treatment and placebo group respectively at baseline . Conclusion Results from this study show that the moderate prevalence and low intensity of STH infection in these preschool children necessitates systematic treatment of the children in child health programmes . Trial Registration Current controlled trials IS RCT N44215995 Anthelmintic treatment of sick preschool-age children at health facilities is a potentially effective strategy for intestinal helminth control in this age-group . We conducted a study from July 1998 to February 1999 in western Kenya to determine whether the Integrated Management of Childhood Illness ( IMCI ) guidelines ' clinical assessment can be used to identify helminth-infected children , and to evaluate the nutritional benefit of treating sick children without pallor with an anthelmintic ( mebendazole is already part of IMCI treatment for sick children aged 2 - 4 years with palmar pallor in areas where hookworm and Trichuris trichiura infections are endemic ) . Sick children aged 2 - 4 years seen at 3 rural health facilities were clinical ly evaluated and tested for haemoglobin concentration , malaria parasites , and intestinal helminths . Children without pallor were r and omly assigned to receive a single dose of 500 mg of mebendazole or a placebo and re-examined 6 months later . Among the 574 children enrolled , 11 % had one or more intestinal helminths . Most infections were of light intensity . Selected clinical signs and symptoms available from the IMCI assessment , including palmar pallor and low weight-for-age , were not associated with helminth infection . Six months after enrollment , no differences in growth of children without pallor were observed between the mebendazole ( n = 166 ) and placebo ( n = 181 ) groups . However , there was a significantly greater mean increase in weight , height , and weight-for-age Z score among the helminth-infected children in the mebendazole group ( n = 22 ) as compared with helminth-infected children in the placebo group ( n = 20 ) . We conclude that even lightly infected preschool-age children without palmar pallor benefit from anthelmintic treatment ; however , in this study setting of low helminth prevalence and intensity , helminth-infected children could not be identified using the IMCI guidelines . Cost-effectiveness studies are needed to help define helminth prevalence thresholds for routine anthelmintic treatment of sick preschool-age children seen at first-level health facilities This study examined the relationship between intestinal helminthiases and growth in urban slum schoolchildren . Children ( n = 330 ) who received single doses of either pyrantel , albendazole , or placebo at baseline and again at 6 months were followed and examined fully at 0 , 3 , 6 , and 12 months for helminth infections and anthropometry . Results of treatments indicated that all groups reduced their prevalence and intensity toward the period of the study . Reductions in intensity of both infections in the treatment groups were observed large in 3 and 12 months , whereas at 6 months reached mostly the initial level of infection . There was no significant difference in growth changes between the dewormed ( once and twice ) and the placebo groups . However , after controlling for some potential confounding factors , there was a significant relationship between reduction of A. lumbricoides infection and height gain at 3 and 12 months ( both P < 0.05 ) . In addition , there was a significant association between reduction in T. trichiura infection and increased midarm circumference at 3 and 12 months ( P < 0.002 and P < 0.08 , respectively ) . We conclude that treatment of helminth infections in school-age children may improve growth in areas where malnutrition and helminth infections are prevalent The impact of albendazole ( 400 mg ) and praziquantel ( 40 mg/kg body weight ) treatment of schoolchildren was compared with placebo according to the presence of anaemia ( haemoglobin concentration < 11 . 0 g/dl ) and heavy ( > 5000 epg ) or light ( < 5000 epg ) hookworm egg load . The study was conducted in rural Tanga . Medication was administered in September 1994 and children were followed-up in January 1995 . Overall , anthelminthic treatment reduced the fall in haemoglobin concentration compared with that observed in the placebo group ( - 0.11 g/dl vs. - 0.35 g/dl ; P = 0.02 ) . Anthelminthic treatment was of greatest benefit to the 9 % of children with both anaemia and heavy hookworm egg load ( + 0.67 g/dl vs. - 0.67 g/dl ) and was also of significant benefit to the 38 % of children with anaemia and light hookworm egg load ( + 0.07 g/dl vs. - 0.21 g/dl ) . It was of no significant benefit to children who were not anaemic . This study suggests that single-dose anthelminthic treatment distributed in schools in this area achieves haematological benefits in nearly half of children infected with S. haematobium and geohelminths ( 37 % of total population ) A sample of 471 pre-school children who frequented schools and crêches in a poor district of Manaus ( Amazonas ) , Brazil , were r and omly su bmi tted to faecal parasitological tests . Two-hundred- and -forty children from both sexes between the ages of 3 and 7 years with Ascaris lumbricoides and /or Giardia lamblia were selected . The objective of the study was to determine the possible influence of these two intestinal parasites and vitamin A and /or zinc supplementation on the serum retinol levels of primary school children . The children were su bmi tted to clinical and anthropometric examinations , dietary interviews and biochemical examinations of retinol and carotene in the serum and of zinc in the hair . The parasitic incidence was 85.0 % and about 54 % of the children were polyparasitic . During the pretreatment phase , the retinol and carotene serum levels were 36 % and 57 % , respectively , below the normal levels . Using the Waterlow classification , the anthropometric analyses revealed that 88 % of the children showed normal growth . A significant effect was observed of the anti-parasitic medicine on the serum retinol levels BACKGROUND We aim ed to find out whether symptomless infection with Trichuris trichiura is associated with impairment of growth and to assess the effect of a multiple-doses regimen of anthelmintic drugs on the growth of children . METHODS In a community based trial , 622 Mexican children were r and omly allocated one of three treatment regimens : 3 days of albendazole 400 mg daily ( high efficacy ) ; one dose of albendazole 400 mg ( moderate efficacy ) ; one dose of pyrantel ( pyrantel embonate ) 11 mg/kg ( low efficacy ) . Growth was monitored for 12 months . Analyses were by intention to treat . FINDINGS 113 ( 18 % ) children were lost to follow-up--34 from the pyrantel group , 45 from the albendazole 400 mg group , and 34 from the albendazole 1200 mg group . Among the 127 children with heavy pretreatment infections , albendazole 1200 mg was better than pyrantel in terms of an increase in arm circumference ( mean 0.26 cm , p=0.044 ) . Among the 381 children with low pretreatment levels of infection , changes in weight ( mean difference between groups -0.33 kg , p=0.036 ) , arm circumference ( -0.18 cm , p=0.0095 ) , and thickness of triceps skinfold ( -0.41 mm , p=0.0031 ) were less in children on albendazole 1200 mg than in those on pyrantel . INTERPRETATION Symptomless trichuriasis impairs growth and albendazole or pyrantel may affect growth , independently of a therapeutic action on parasites . Possible toxic effects of high-dose albendazole require further investigation This r and omized , placebo-controlled trial investigated the tolerance , efficacy , and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis . Children were infected with Ascaris ( 30.7 % ) , Trichuris ( 53.4 % ) , and hookworm ( 9.7 % ) with 69.9 % having more than one of these parasites . A total of 15.8 % of the children had Wuchereria bancrofti microfilariae . Children were r and omly assigned treatment with placebo , albendazole ( ALB ) , diethylcarbamazine ( DEC ) , or combined therapy . The combination of DEC/ALB reduced microfilarial density compared with placebo , ALB , or DEC ( P < or = 0.03 ) . Albendazole and DEC/ALB reduced the prevalence of Ascaris , Trichuris , and hookworm more than placebo or DEC ( P < or = 0.03 ) . Among Trichuris-infected children , those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo ( P < or = 0.05 ) . Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia , DEC/ALB was more effective than DEC , with no increase in severity of adverse reactions Summary Single interventions for helminthic infections and micronutrient deficiencies are effective , but it is not clear whether combined interventions will provide equal , additive or synergistic effects to improve children 's health . The study objective was to determine the impact of single and combined interventions on nutritional status and scholastic and cognitive performance of school children . A double-blind , r and omized , placebo-controlled trial in 11 rural South African primary schools r and omly allocated 579 children aged between 8 and 10 years into six study groups , half of whom received antihelminthic treatment at baseline . The de-wormed and non-de-wormed arms were further divided into three groups and given biscuits , either unfortified or fortified with vitamin A and iron or with vitamin A only , given daily for 16 weeks . The outcome measures were anthropometric , micronutrient and parasite status , and scholastic and cognitive test scores . There was a significant treatment effect of vitamin A on serum retinol ( p < 0.01 ) , and the suggestion of an additive effect between vitamin A fortification and de-worming . Fortified biscuits improved micronutrient status in rural primary school children ; vitamin A with de-worming had a greater impact on micronutrient status than vitamin A fortification alone and antihelminthic treatment significantly reduced the overall prevalence of parasite infection . The burden of micronutrient deficiency ( anaemia , iron and vitamin A ) and stunting in this study population was low and , coupled with the restricted duration of the intervention ( 16 weeks ) , might have limited the impact of the interventions To investigate the relationships between helminth infections and iron status among school-aged children , 1,115 Tanzanian children in grade s 2 through 5 were r and omly assigned to treatment or control groups . The children in the treatment group were screened for infection with Schistosoma haematobium and hookworm at baseline , 3 months , and 15 months ; infected children were given albendazole against hookworm and praziquantel against schistosomiasis . The control group received a placebo and did not undergo parasitological screening until 15 months after the baseline . Hematological variables were compared between the treatment and control groups . The main results were , first , that the hemoglobin concentration significantly improved after treatment for hookworm ( p < .001 ) by 9.3 g/L in children treated for hookworm only and by 8.8 g/L in children treated for hookworm and schistosomiasis . The ferritin concentration also improved in children treated for schistosomiasis ( p = .001 ) or hookworm ( p = .019 ) . Second , a longitudinal analysis of the data from the children in the control group showed that hookworm and schistosomiasis loads were negatively associated with hemoglobin and ferritin concentrations . Moreover , ferritin concentrations increased as C-reactive protein levels increased . Overall , the results showed that anthelmintic treatment is a useful tool for reducing anemia in areas with high hookworm and schistosomiasis endemicity . The empirical relationship between ferritin and C-reactive protein indicated that simple procedures for adjusting cutoff points for the use of ferritin as an indicator of low iron stores were unlikely to be useful in this population This study aim ed to determine the effect of a multiple-micronutrient-fortified beverage on the micronutrient status , physical fitness , and cognitive performance of schoolchildren . The study was a r and omized , double-blind , placebo-controlled trial of schoolchildren assigned to receive either the fortified or nonfortified beverage with or without anthelmintic therapy . Data on hemoglobin level , urinary iodine excretion ( UIE ) level , physical fitness , and cognitive performance were collected at baseline and at 16 weeks post-intervention . The fortified beverage significantly improved iron status among the subjects that had hemoglobin levels < 11 g/dl at baseline . The proportion of children who remained moderately to severely anemic was significantly lower among those given the fortified beverage . In the groups that received the fortified product , the median UIE level increased , whereas among those who received the placebo beverage , the median UIE level was reduced significantly . Iron- and /or iodine-deficient subjects who received the fortified beverage showed significant improvements in fitness ( post-exercise reduction of heart rate ) and cognitive performance ( nonverbal mental ability score ) . The study showed that consumption of a multiple-micronutrient-fortified beverage for 16 weeks had significant effects on iron status , iodine status , physical fitness , and cognitive performance among iron- and /or iodine-deficient Filipino schoolchildren . Anthelmintic therapy improved iron status of anemic children and iodine status of the iron-adequate children at baseline but it had no effect on physical fitness and cognitive performance . The results from the clinical study showed that a multiple-micronutrient-fortified beverage could play an important role in preventing and controlling micronutrient deficiencies Stool specimens from a sample of schoolchildren at six schools in Kweneng District were examined for hookworm infection , using the brine flotation method . Necator americanus was the only hookworm identified . The western part of the District forms part of the Kalahari Desert , and in four villages here 90 % , 88 % , 88 % and 86 % of the children were infected . In two villages in the eastern non-desert part , only 13 % and 9 % were infected . Most infections were light . There was no significant correlation between severity of infection and anaemia . In one school ( 228 pupils ; 86 % infected with hookworm ) , half the children were treated with tetrachloroethylene ( 0.1 ml/kg , maximum 5 ml ) and the other half with placebo . Two weeks after treatment the prevalence of infection were 28 % and 75 % respectively ( p less than 0.001 ) , and five months after treatment 51 % and 69 % ( p less than 0.05 ) . Measured over the five-month period there were no significant changes in haemoglobin and nutritional status ( weight/height ) . Based on the results of the survey , a hookworm mass treatment programme was not recommended The study examines the effect of moderate to high worm burdens of Trichuris trichiura infection on the cognitive functions of 159 school children ( age 9–12 years ) in Jamaica , using a double-blind placebo-controlled protocol . Results were evaluated by using a forward-stepwise multiple linear regression . Removal of worms led to a significant improvement in tests of auditory short-term memory ( p < 0.017 ; p < 0.013 ) , and scanning and retrieval of long-term memory ( p < 0.001 ) . Nine weeks after treatment , there were no longer significant differences between the treated children and an uninfected Control group in these three tests of cognitive function . It is concluded that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy The study was conducted to investigate the impact of intestinal helminthiasis and treatment on iron status and acute phase response ( APR ) among urban Indonesian primary school children , aged 8 - 11 years old . The prevalence of helminthiasis among these children was ; Ascaris lumbricoides , 81.6 % ; Trichuris trichiura , 88.3 % ; and mixed infection of A. lumbricoides and T. trichiura , 70.0 % . Of 120 children enrolled in the investigation , 59 received a single 400 mg dose of albendazole , and 61 received a placebo . Ten days following treatment , the prevalence of ascariasis and trichuriasis in the treatment group diminished to 0 % and 27 % , respectively , and in the placebo group to 63.9 % and 68.9 % . Plasma iron , hemoglobin , C-reactive protein ( CRP ) , erythrocyte sedimentation rate ( ESR ) , white blood cell ( WBC ) , interleukin-1 ( IL-1 ) , interleukin-6 ( IL-6 ) and tumor necrosis factor ( TNF ) concentrations were determined prior to the intervention and 10 days after . Plasma iron concentrations and WBC count rose in the treatment group ( p= < or = 0.05 ) when compared to baseline status . Increases in hemoglobin concentrations observed in the treatment group 10 days post-treatment were not statistically significant . CRP , IL-1 , IL-6 and TNF were found to be within normal limits for both groups both before and after treatment . ESR increased significantly in both treatment and placebo groups when compared the rates measured before treatment . These findings show that treatment with albendazole is associated not only with a decreased worm burden in school children , but also a rise in plasma iron OBJECTIVE To study the clinical efficacy and the incremental cost-effectiveness of albendazole in improving the nutritional status of pre-school children . DESIGN Single blind , placebo-controlled trial with child as the unit of r and omization . SETTING In the Anganwadi centers of the Integrated Child Development Services situated in the urban slums of Lucknow , North India . METHODS Thirty-two Anganwadi centers were r and omly selected for the trial . Included were registered resident children between 1.5 to 3.5 years of age with informed and written parental consent . The intervention group received 600 mg of albendazole powder every six months while the placebo group received same quantity of calcium powder . Enrolled children were contacted once in six months from January 1995 to 1997 and given treatment . The outcome measure were change in the proportion of underweight ( weight for age < -2.00z ) , stunted ( height for age < -2.00z ) children and the cost per child prevented from becoming stunted . RESULTS There were 610 and 451 children in the albendazole and placebo groups , respectively . Mean age at recruitment was 31.8 months ( SD : 9.7 ) . Follow-up and compliance in both the groups was > 95 % . During the 2 year follow-up , the proportion of stunted children increased by 11.44 % and 2.06 % in the placebo and albendazole groups , respectively , and the difference was 9.38 % ( 95 % CI 6.01 % to 12.75 % ; p value < 0.0001 ) . Direct fecal smear was positive for the ova of ascaris in 41.2 % and 55.3 % children in the albendazole and placebo groups , respectively at the end of the study ( p value < 0.001 ) . The annual family expenditure on illness in the recruited child was Rs . 743 ( SD : 662 ) and Rs . 625 ( SD : 609 ) in the albendazole and the placebo groups , respectively . The incremental cost-effectiveness ratio was Rs 543.00 for each case of stunting prevented with albendazole . There was no difference in the various morbidity or cognitive performance , as judged by the revised Denver prescreening question naire , in both the groups at enrollment as well as at the end of the study . CONCLUSIONS Six monthly albendazole reduces the risk of stunting with a small increase in the expenditure on health care from the payer 's perspective . Larger trials are needed to study the effect of albendazole on prevention of stunting , cognitive functions and all-cause childhood mortality Objective : Anemia is a major public health problem caused by multiple factors . Vitamin A ( VA ) depletion can affect hemoglobin concentration ( Hb ) . This study investigated the improvement in Hb and VA status in preschool Indonesian children following supplementation with 210 μmol VA and deworming with 400 mg albendazole . Subjects and design : Indonesian children ( n=131 ) infected with Ascaris lumbricoides and /or Trichuris trichiura were enrolled . The children were grouped by length of time since receiving 210 μmol VA through the local health system . Group 1 ( VA administered ≥4 month before baseline ) included 51 children with Ascaris and 29 children with Trichuris . Group 2 had received VA ≤1 month of baseline from the local health post and included 51 children . Intervention and methods : Immediately following baseline Hb and VA status assessment ( modified relative dose response ( MRDR ) test ) , Group 1 children were given 210 μmol VA and 400 mg albendazole . Group 2 were r and omized to be dewormed either 1 week before , at the same time or 1 week after baseline MRDR and Hb measures . Follow-up assessment was 3–4 weeks after baseline . Results : VA status in Group 1 significantly improved in children with either Ascaris ( P<0.0001 ) or Trichuris ( P=0.028 ) . Although the prevalence of anemia declined , the improvement in Hb was not significant ( P=0.08 ) . In Group 2 , improvement in VA status from the VA delivered through the public health system was maintained for more than 1 month . Hb improved ( P=0.0037 ) and this improvement appeared to be associated with the length of time between deworming and follow-up assessment s. Conclusion : Public health supplementation programs to improve VA status may also increase Hb concentrations and decrease anemia prevalence , especially when linked to deworming . Sponsorship : These studies were supported by the Thrasher Research Fund , SmithKline Beecham and Hatch-Wisconsin Agricultural Experiment Station number WIS04533 A 2-year investigation , consisting of a controlled , non-blind , 3-monthly chemotherapeutic intervention trial , based on transmission dynamics of Ascaris lumbricoides infection , was undertaken to prove or refute the role of A. lumbricoides as a contributor to childhood malnutrition . The study involved 1206 children aged 2 - 12 years in 21 villages in Myanmar [ Burma ] starting in August 1984 . The intervention and non-intervention villages were comparable regarding almost all the important baseline variables , including prevalences of Ascaris infection ( 80.8 vs 83.0 % ) and of malnutrition of grade 2 and above for height-for-age ( 58.4 vs 55.8 % ) and for weight-for-age ( 48.2 vs 47.8 % ) . The intensity of Ascaris infection was related to the degree of malnutrition . A significant increment of height gain was found , starting after the 6th month , and of weight gain after the 24th month , of the study among the treated 2 - 10 years old children when compared with the non-treated ones . By the end of 24 months , the height and weight gains per child were 0.65 cm and 0.93 kg respectively . Lesser increments in height-for-age and weight-for-age were also observed after successive treatments among the treated children with initially higher mean worm burdens . The findings are discussed in the context of causal relationship between ascariasis and malnutrition in children OBJECTIVES To determine the epidemiology of helminthic infections and the efficacy of parasite treatment among rural South African primary school children in the province of KwaZulu-Natal . To assess the South African government 's parasite control policy . METHODS The study recruited 268 school children , aged 8 to 10 , and r and omly allocated them into treatment and placebo groups ( treatment consisted of a single dose of albendazole ( 400 mg ) and praziquantel ( 40 mg/kg ) ) . Anthropometric measurements and the prevalence and intensity of helminth infections were taken at baseline ( prior to treatment ) and 16 weeks post treatment . Two weeks after treatment prevalence and intensity were again measured for an approximate 50 % sub- sample of the children to investigate efficacy of treatment . An analysis of the South African government 's policies concerning parasite control is assessed in the light of these epidemiological findings . RESULTS Low levels of both stunting and wasting were observed throughout the study ( approximately 10 % and 1 % , respectively ) , but did not vary significantly across either treatment group or time period ( P > 0.50 ) . At baseline the observed prevalences for the three main helminths found in this study among the treated children were Ascaris lumbricoides 29.5 % , Trichuris trichiura 51.9 % and Schistosoma haematobium 22.3 % . These prevalences declined significantly to 4.7 % ( P < 0.0005 ) , 38.0 % ( P < 0.03 ) , and 3.3 % ( P < 0.0002 ) , respectively , 16 weeks post treatment . The majority of infections observed at baseline were of light intensity , namely A. lumbricoides ( 50 % ) , T. trichiura ( 80 % ) and S. haematobium ( 100 % ) , and following treatment these levels were reduced significantly ( P < 0.0001 , P < 0.05 and P < 0.005 , respectively ) . The levels of both prevalence and intensity in the untreated group remained constant . The cure rates over the first two weeks of the study were found to be 94.4 % for A. lumbricoides , 40 % for T. trichiura and 72.2 % for S. haematobium . CONCLUSION The benefits of targeted , school-based treatment in reducing the prevalence and intensity of infection supports the South African government 's focus of using school-based interventions as part of an integrated parasite control programme . These strategies and programmes are consistent with recommendations of the World Health Organization ( WHO ) and The United Nations Children 's Fund ( UNICEF ) Previous data from Vietnam show that anaemia is highly prevalent among schoolchildren , who are considered not to be iron deficient . Trichuris infection doubled the risk of anaemia . The present study aim ed to evaluate the hypothesis that de-worming is more effective than iron fortification in an anaemic , infection-prone population . In a trial with a 2 x 2 factorial design , 425 anaemic children aged 6 - 8 years were r and omly assigned to receive either iron-fortified noodles or placebo , and mebendazole or placebo . Outcomes considered were change in haematological indicators of iron status ( Hb , serum ferritin ( SF ) , serum transferrin receptor ( TfR ) and haemoglobinopathies analysis ) ; inflammations ( C-reactive protein ( CRP ) ) ; parasite infection status ( hookworm , Trichuris and Ascaris infection ) ; and IgE. ANOVA and logistic regression were used to assess the effects of iron fortification and de-worming on Hb , SF , TfR , body iron and anaemia . Hb improved in all groups after 6 months of intervention . Iron fortification significantly improved Hb , SF and body iron ( 2.6 g/l , 16.3 microg/l and 1 mg/kg , respectively ) . Prevalence of elevated IgE was very high at baseline ( 99 % ) and significantly reduced to about 75 % in all groups after intervention . De-worming unexpectedly showed no effect on Hb , iron status and IgE level . It is concluded that iron fortification slightly improved anaemia and iron status in anaemic schoolchildren in rural Vietnam that were not considered iron deficient . Chronic infection or other unidentified factors may play an important role in the seasonal reduction of anaemia seen in all treatment groups The effects of mild to moderate infections of Trichuris trichiura on cognitive functions were investigated in Jamaican children aged 7 to 10 years . In all , 189 infected children and 100 uninfected classmates were studied . The infected children were r and omly assigned to receive treatment ( albendazole ) or a placebo . All children were given cognitive tests on enrolment and 14 weeks later . These included verbal fluency ( generation of ideas ) , digit span ( working memory ) , number choice ( speed of processing of visual stimuli ) , visual search ( sustained attention ) and a French Vocabulary test ( paired-associate learning ) . At baseline , the infected children had lower scores than the uninfected ones in fluency ( P = 0.01 ) , search ( P = 0.02 ) and French ( P = 0.01 ) . Treatment effects were examined among infected children and there was no significant treatment effect for any of the tests . However , there was a significant treatment by weight-for-age interaction in fluency ( P < 0.05 ) . The children with low weight-for-age ( Z-score < -1 ) improved with treatment while there was no improvement with treatment among the other children . We concluded that treatment of children with mild to moderate T. trichiura infections using albendazole produces little benefit in cognition if they are adequately nourished ; however , undernourished children are more likely to benefit Objective : To assess the effects of multi-micronutrient supplementation and multi-helminth chemotherapy on serum retinol concentration , using schools as a health delivery system . Study area and population : From 19 primary schools in Bondo District , western Kenya , 977 children between 9 and 18 y were included in the trial . The 644 ( 65.9 % ) children on whom baseline serum retinol was available were included in this study . Design : A r and omised , placebo-controlled , double-blind , two-by-two factorial trial on the effects of multi-micronutrient supplementation and multi-helminth chemotherapy on serum retinol after 8 months . Intervention : Single treatment with albendazole ( 600 mg ) and praziquantel ( 40 mg/kg of body weight ) and daily multi-micronutrient supplementation with tablet containing 1000 µg vitamin A. Results : Micronutrient supplementation ( 0.08 µmol/l , 95 % CI 0.01 , 0.14 ; P=0.025 ) , but not treatment ( 0.03 µmol/l , 95 % CI −0.04 , 0.10 ; P=0.38 ) , increased serum retinol . However , treatment did increase serum retinol in S. mansoni-infected ( 0.09 , 95 % CI 0.02 , 0.16 ; P=0.009 ) , but not in uninfected children ( −0.07 , 95 % CI −0.18 , 0.03 ; P=0.18 ; interaction , P=0.01 ) . Similarly , reduction in egg output of S. mansoni , but none of the geohelminth , was a predictor , corresponding to a 0.008 µmol/l ( 95 % CI 0.00002 , 0.02 ; P=0.049 ) increase in serum retinol per 100 epg reduction . Interestingly , interactions were found between age and sex ( P=0.046 ) , and malaria parasitaemia and sickle cell phenotype ( P=0.04 ) . Conclusion : Multi-micronutrient supplementation and reduction in S. mansoni egg output increased serum retinol , irrespective of initial serum retinol . Sponsorship : The Danish International Development Assistance We studied physical fitness , as determined by the Harvard Step Test ( HST ) , and appetite , as measured by the consumption of a morning snack ( maize meal porridge ) , in primary school boys infected with Schistosoma haematobium ( 100 % baseline prevalence ) and hookworm ( 94 - 100 % prevalence ) who received a single dose of metrifonate ( MT , 10 mg/kg body weight ) or praziquantel ( PR , 40 mg/kg body weight ) , or a placebo ( PL ) . Five weeks after treatment , HST scores and porridge intake increased significantly in the MT and PR groups , but the PL group did not change . At the second examination , the MT group showed a significant decrease in S. haematobium egg counts ( mean = 180 vs. 14 eggs/10 ml adj , P less than 0.0002 , 82 % egg reduction in arithmetic means ) as did the PR group ( mean = 198 vs. 0.1 eggs/10 ml adj , P less than 0.0002 , 99.9 % reduction ) ; the egg counts in the PL group did not change . The MT group also exhibited a significant decrease in hookworm egg counts ( mean = 1,550 vs. 75 eggs per gram feces [ epg ] , P less than 0.0005 , 80 % reduction ) . Treatment with either drug may allow improved physical fitness and appetite in areas where S. haematobium and protein-energy malnutrition are highly prevalent OBJECTIVE To determine whether successful deworming for 6 months in children with high levels of Ascaris improves physical growth . SUBJECTS Two hundred twenty-eight children ( mean age , 9.7 years ) in a highl and Indian town in Guatemala . DESIGN Children were r and omly assigned to receive albendazole or placebo at baseline and 12 weeks . Children and field workers were both blind to the group assignment . OUTCOME MEASURES Children 's heights , weights , and mid-upper-arm circumferences were measured at baseline and 12 and 24 weeks . Fecal egg counts were taken at 0 , 2 , 12 , 14 , and 24 weeks to estimate the helminth burden ( eggs per gram of feces [ epg ] ) . RESULTS Baseline helminth prevalences were Ascaris , 91 % , and Trichuris , 82 % . Ascaris intensities were high : half of the children had moderate burdens ( 10 000 to 50 000 epg ) , and 25 % had heavy burdens ( > 50 000 epg ) . Trichuris burdens were light ( 72 % < 1000 epg ) . The albendazole and placebo groups did not differ at baseline in epg , age , anthropometry , or socioeconomic status . The two rounds of treatment successfully reduced the Ascaris burdens but had less effect on Trichuris . At 6 months the treatment group showed a small gain in weight ( 0.18 kg ) compared with the placebo group but no improvement in height or mid-upper-arm circumference . CONCLUSIONS The successful removal of ascaris in a population of school-aged children with relatively high loads may have modest effects on weight gain . Ascaris is one of the most common infections in school-aged children , but its effect on the host may be less than that of other helminths We studied physical fitness with the Harvard step test ( HST ) , in primary schoolboys infected with hookworm ( 91 % baseline prevalence ) , Trichuris trichiura ( 94 % ) and Ascaris lumbricoides ( 39 - 40 % ) who received a single 400 mg dose of albendazole or an identical placebo . Boys were examined , allocated at r and om to placebo or albendazole groups , treated , and re-examined 7 weeks later . The 2 groups did not differ significantly before treatment in age , anthropometry , haemoglobin levels , prevalence or intensity of the 3 helminth infections , or in initial HST fitness scores and heart rates . Seven weeks after treatment , the albendazole group ( n = 18 ) exhibited significant improvements in fitness scores and heart rates at 1 , 2 , 3 , and 4 min after the HST while in the placebo group ( n = 15 ) these quantities had not changed significantly . After treatment , the albendazole group had significant decreases in the logarithmic egg counts for hookworm ( 80 % reduction in arithmetic means ) and A. lumbricoides ( 100 % reduction ) ; T. trichiura egg counts did not change significantly . The placebo group showed a borderline increase in the logarithms of hookworm egg counts and no significant change in T. trichiura and A. lumbricoides egg counts . Multiple regression analysis showed that the significant linear predictors of increase in HST score after treatment were decrease in resting heart rate after treatment , and decreases in hookworm egg counts and logarithms of A. lumbricoides egg counts after treatment . We conclude that single dose treatment with albendazole , despite continual exposure to reinfection , can allow improved physical fitness in schoolboys in areas where soil-transmitted helminths and protein-energy malnutrition are highly prevalent An 18-month study was conducted from February 1989 to August 1990 to examine the effect of regular deworming on child growth and nutritional status . A sample of 1402 children , from 2 to 6 years old , were divided into a treatment group and a control group . The 688 children in the treatment group received a 500 mg single dose of mebendazole , while the 714 children in the control group were given a placebo . Height , weight and mid-upper arm circumference ( MUAC ) were measured on monthly household visits . Growth was measured in terms of the change in height-for-age , weight-for-age , weight-for-height and MUAC over 18 months . The initial prevalence of infection was estimated from a r and om sample of 96 children ( 49 treated , 47 control ) . The initial overall prevalence of Ascaris lumbricoides , Trichuris trichiura and hookworm was 71 , 44 and 10 % respectively . The final prevalence of infection , estimated from a r and om sample of 265 children , was A. lumbricoides 6 % , T. trichiura 6 % and hookworm 2 % in the mebendazole group compared with 64 , 18 and 19 % respectively in the placebo group . Despite the successful treatment of helminths , there was no significant improvement in the growth of treated children compared with their untreated counterparts in terms of the change in z-scores of height-for-age , weight-for-age , weight-for-height and MUAC . The factors which may have contributed to this outcome are discussed Appetite and growth were studied in primary schoolboys ( 6 - 10 years ) infected with Ascaris lumbricoides ( 86 % ) and Trichuris trichiura ( 100 % ) who received a single dose of pyrantel pamoate ( which has little or no effect on Trichuris trichiura ) or a placebo . Boys were examined , allocated at r and om by descending Ascaris egg count to pyrantel ( PR , n = 36 ) or placebo ( PL , n = 36 ) groups , treated , and re-examined 3 and 7 weeks later . The 2 groups did not differ significantly before treatment in helminth infections , appetite , or growth . Three and 7 weeks after treatment , the PR group exhibited significantly greater increases than did the PL group in weight ( 0.2 kg and 0.4 kg more , respectively ) and percentage weight-for-age ( 0.6 % and 1.7 % points more , respectively ) . Appetite increased significantly in the PR group at 3 and 7 weeks ( P < 0.0005 and P < 0.01 , respectively ) but not in the PL group . The prevalence and intensity of A. lumbricoides infection were greatly reduced in the PR group at 3 and 7 weeks ( both P < 0.0001 ) but not in the PL group . We conclude that treatment with pyrantel pamoate may improve appetite and growth in school children in areas where A. lumbricoides infections and poor growth are highly prevalent To comprehend the result of a r and omized controlled trial ( RCT ) , readers must underst and its design , conduct , analysis and interpretation . That goal can be achieved only through complete transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by using a checklist and flow diagram . The revised CONSORT statement presented in this article incorporates new evidence and addresses some criticism of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Comment . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage or participants through an RCT . The revised flow diagram depicts information from 4 stages of a trial ( enrollment , intervention allocation , follow-up and analysis ) . The diagram explicitly includes the number of participants , according to each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting or an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Abstract Objective To estimate the effectiveness of delivering an anthelmintic through a community child health programme on the weight gain of preschool children in Ug and a. Design Cluster r and omised controlled trial . Setting Eastern Ug and a. Participants 48 parishes participating in a new programme for child health : 24 offered children an additional service of anthelmintic treatment . The outcome is based on measurements from 27 995 children . Intervention Treatment of children aged between 1 and 7 years with 400 mg albendazole added to st and ard services offered during child health days over a three year period . Main outcome measure Weight gain . Results The provision of periodic anthelmintic treatment as a part of child health services in Ug and a result ed in an increase in weight gain of about 10 % ( 166 g per child per year , 95 % confidence interval 16 to 316 ) above expected weight gain when treatments were given twice a year , and an increase of 5 % when the treatment was given annually . Conclusion Deworming of preschool children in Ug and a as part of regularly scheduled health services seems practical and associated with increased weight gain We studied asymptomatic primary schoolchildren in northeastern Malaysia with light to moderate trichuriasis to determine the effect of albendazole treatment on growth rates and TNF-alpha levels . Thirty-seven schoolchildren aged 6 - 7 years with stool sample s positive for Trichuris trichiura and negative for other geohelminths and protozoa were r and omized to receive albendazole 400 mg or a placebo daily for 2 days . Anthropometric parameters at baseline , 3 , 6 and 12 months were compared between the 2 groups . The placebo group had a significantly greater increase in height ( p = 0.04 ) than the albendazole treatment group . There were no significant differences in urinary TNF-alpha levels ( p = 0.8 ) between the 2 groups and no significant changes between baseline and 1 month post-treatment levels . Further studies are needed to determine the etiology of this apparent association between the albendazole treatment group and the delay in growth rate at 6 months post-treatment Intestinal helminths are among the most common infections in school-age children . Of 246 children , aged 7 - 12 years , attending school in rural Guatemala , 91 % carried Ascaris lumbricoides and 82 % carried Trichuris trichiura . These children were r and omly assigned to receive either albendazole or placebo at 0 and 12 weeks in a ' double-blind ' study of the effects of deworming on indicators of school performance . Albendazole successfully rid the children of Ascaris but it was less effective against Trichuris . The children 's performance in tests of reading and vocabulary were measured at 0 and 24 weeks , the Peabody picture vocabulary test was given at 24 weeks , and attendance was measured throughout the school year . Comparison of the treated and placebo groups showed no positive effect of deworming . The treated children were largely free of Ascaris for at least 6 months , but during that period we could not detect any improvement in reading , vocabulary , or attendance . The effects of being Trichuris-free were not examined because of the limited effectiveness of albendazole against this worm at the dosage used Relationships between hemoglobin level and S. hematobium , hookworm , and malarial infection before and six months after metrifonate treatment were studied in Kenyan primary school children in an area where anemia , S. hematobium and hookworm are common ( prevalences 61 % , 46 % , and 95 % , respectively ) and malaria is holoendemic . The mean hemoglobin level in children from one school , both with and without S. hematobium infection ( n = 250 ) , was significantly lower in children with higher S. hematobium egg counts , heavier hookworm infections , positive Plasmodium slides , and larger spleens . All children with light-moderate S. hematobium infection ( 1 - 500 eggs/10 ml adj ) in four schools were examined ( Exam 1 ) , allocated at r and om to either placebo ( MIP , n = 198 ) or metrifonate treatment ( MIT , n = 202 ) groups , treated , and examined again six months later ( Exam 2 ) . Hemoglobin levels rose significantly in both groups between exams , but the rise in the MIT group was 30 % higher than in the MIP group ( 1.3 vs. 1.0 g/dl , P less than 0.014 ) . The increase in hemoglobin level in the MIT group was significantly and positively correlated with decreases between exams in S. hematobium and hookworm egg counts and with higher malarial parasite counts at Exam 1 ( Pearson r 's 0.21 , 0.20 , 0.20 , respectively , P less than 0.01 ) . A stepwise multiple regression equation using hemoglobin rise between exams as the dependent variable showed that decreases in S. hematobium and hookworm egg counts were equally important determinants of hemoglobin rise and that malarial parasite count was almost as important as the changes in intensities of the helminth infections . These results show that treatment for S. hematobium with metrifonate can increase hemoglobin levels in children in an area where S. hematobium and anemia are common . They also emphasize the importance of measuring multiple parasitic infections and using multivariate statistical techniques such as multiple regression analysis in order to define the relationships between parasitic infections and morbidity To access the effectiveness of the treatment of soil-transmitted helminthiasis ( STH ) on the growth of primary school children , 353 children were block stratified to receive either mebendazole plus pyrantel oxantel pamoate every three months or a placebo . The children were followed for two years with 89 % completing the trial . Follow-up stools indicated that the treatment was efficacious for ascariasis and trichuriasis . There was virtually no hookworm infection . The children were malnourished as measured by the number below -2 SD of height and weight st and ards . There was no difference in height or weight between the treatment and control groups by sex initially or at the end of two years of follow-up . The treatment of Ascaris and Trichuris had no effect on growth parameters . The effect of STH on growth may be mediated through hookworm infections BACKGROUND Epidemiological studies have shown inverse associations between geohelminth ( intestinal helminth ) infection and atopy , leading to the suggestion that geohelminths might protect against allergy . Periodic deworming of school children with anthelmintics is a widely implemented intervention and has raised concerns that such programmes could increase allergy . We investigated the effect of repeated anthelmintic treatments with albendazole over 12 months on the prevalence of atopy and clinical indices of allergy . METHODS We did a cluster-r and omised controlled trial in schoolchildren from 68 rural schools . Children were r and omly assigned by school to either albendazole ( 34 schools , 1164 children ) every 2 months for 12 months , or to no intervention ( 34 schools , 1209 children ) . The intervention schools received a total of seven albendazole treatments . The primary outcome was atopy at 12 months ( allergen skin-test reactivity ) , and analysis was by intention-to-treat for whole-school analyses and per protocol for children . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N61195515 . FINDINGS Data for analysis were available for all schools and from 67.4 % ( 784 of 1164 ) and 70.1 % ( 848 of 1209 ) of children in albendazole and no-treatment groups , respectively . Albendazole treatment caused large reductions in geohelminth prevalence over the study period ( adjusted odds ratio 0.13 , 95 % CI 0.09 - 0.19 , p<0.001 ) , but there was no evidence that treatment was associated with an increase in atopy prevalence ( 0.97 , 0.68 - 1.39 , p=0.862 ) , or clinical allergy ( wheeze , 1.07 , 0.54 - 2.11 , p=0.848 ) in the albendazole compared with the no-treatment group . INTERPRETATION We saw no increase in the prevalence of atopy or clinical allergy associated with albendazole treatment . Deworming programmes for schoolchildren are unlikely to be accompanied by an increase in allergy This study was undertaken to measure the impact of periodic deworming with albendazole on growth status and incidence of diarrhoea in children aged 2 - 5 years in an urban setting in India and to assess the feasibility of local health workers implementing the procedures involved . This was a double-blind , placebo-controlled , r and omized , community-based intervention trial with 702 children r and omly allocated to receive either albendazole or placebo . The two study groups received two doses of albendazole ( 400 mg ) or placebo six months apart . Mean weight increased significantly in the albendazole group compared to the control group at three months , six months and nine months following treatment ( P<0.01 , P<0.01 and P<0.001 respectively ) . The albendazole group also experienced fewer episodes of diarrhoea than their control counterparts ( relative risk 1.3 , 95 % CI 1.07 - 1.53 ) with a 28 % reduction . The health workers administered the correct dosage satisfactorily and there were no adverse effects . Thus , periodic mass deworming with albendazole would seem to be a safe and effective method that could be adopted at the community level or as an integral part of school health services and could be expected to improve growth and reduce the incidence of diarrhoea in children This r and omized double blind community trial was conducted on Ascaris infested children ( n = 85 ) aged 2 to 12 years and was aim ed to study the impact of deworming on nutritional status , in an urban slum of Dhaka , Bangladesh . The change of weight gain was significantly higher in children given anthelmintics than those given placebo ( 0.92 kg vs. 0.54 kg ) . A multiple linear regression model shows that after controlling sex , deworming and height were positively correlated while age and weight were negatively correlated with weight change A 24-week r and omized double blind intervention trial was conducted on adult female tea pluckers from an estate in Bangladesh to investigate the impact of iron supplementation and anthelmintic treatment on changes in ferritin and haemoglobin levels as well as on prevalence and intensity of helminth infections . A total of 553 women were r and omly assigned to 1 of 4 intervention groups : group 1 received iron supplementation on a weekly basis , group 2 received anthelmintic treatment at the beginning and half way through the trial , group 3 received both iron supplementation as group 1 and anthelmintic treatment as group 2 , and group 4 was a control group and received placebos for both iron supplementation and anthelmintic treatment . Prevalence and intensity of helminth infections ( egg counts/g stool ) of Ascaris lumbricoides , Trichuris trichiura and hookworms significantly fell in the 2 groups receiving anthelmintic treatment and there were some reductions in the 2 groups not receiving anthelminthic treatment . Haemoglobin and haematocrit concentrations increased significantly in the iron supplemented groups with smaller increases in the anthelmintic only group . All women showed a decrease in serum ferritin levels post-trial with greater losses in the 2 dewormed groups . Significant negative associations were found between hookworm egg counts and ferritin levels and Trichuris trichiura egg counts and haemoglobin concentration We studied the growth of primary schoolchildren with hookworm ( 87 % ) , T. trichiura ( 97 % ) , and A. lumbricoides ( 49 % ) who received a single 400 mg dose of albendazole or an identical placebo . Children were allocated at r and om to placebo ( PL , n = 72 ) or albendazole ( A , n = 78 ) groups , treated , and re-examined 6 months later . The A group gained significantly more than the PL group in weight ( 1.3 kg ) , percent weight for age ( 4.5 % age points ) , percent height for age ( 0.5 % age points ) , percent weight for height ( 4.3 % age points ) , percent arm circumference ( 2.9 % age points ) , and in triceps and subscapular skinfold thicknesses ( 1.2 mm ) . The PL group showed significant decreases between exams in percent weight for age , percent height for age , percent weight for height , percent arm circumference for age , and skinfold thicknesses for age . The A group had highly significant increases ( P less than 0.0002 ) in all of these parameters except height for age . From Exam 1 to 2 , the A group exhibited decreases ( P less than 0.0002 ) in geometric means eggs per gram of feces ( epg ) : for hookworm , means = 1,183 epg at Exam 1 vs. 136 epg at Exam 2 ( 67 % egg reduction ) ; for T. trichiura , means = 2,857 epg at Exam 1 vs. 1,061 epg at Exam 2 ( 28 % egg reduction ) ; and for A. lumbricoides , means = 86 epg at Exam 1 vs. 2 epg at Exam 2 ( 91 % egg reduction ) . The PL group had a borderline increase in geometric means hookworm egg count , no significant change in T. trichiura egg count , and a small but significant decrease in A. lumbricoides egg count . Decreases in intensities of all infections were significant predictors of growth improvement . Hookworm egg count entered the equations for all 6 measurements , and A. lumbricoides and T. trichiura entered 4/6 equations . Single dose treatment with albendazole , despite continual exposure to infection , can permit improved growth rates in areas where intestinal helminths and protein-energy malnutrition are highly prevalent A double-blind placebo-controlled study of the concurrent administration of albendazole and praziquantel was conducted in>1500 children with high prevalences of geohelminths and schistosomiasis . The study sites were in China and the Philippines , including 2 strains of Schistosoma japonicum , and 2 different regions of Kenya , 1 each with endemic Schistosoma mansoni or Schistosoma haematobium . Neither medication affected the cure rate of the other . There was no difference between the side effect rate from albendazole or the double placebo . Praziquantel-treated children had more nausea , abdominal pain , and headache but these side effects were statistically more common in children with schistosomiasis , suggesting a strong influence of dying parasites . The subjects were followed for 6 months for changes in infection status , growth parameters , hemoglobin , and schistosomiasis morbidity . In all 4 sites , a significant 6-month increase in serum hemoglobin was observed in children who received praziquantel , strongly supporting population -based mass treatment A r and omized controlled trial in KwaZulu-Natal ( South Africa ) of 428 primary -school pupils ( stratified into 6 groups by age , sex and intervention ) measured the effect of different anthelmintic treatments and iron supplementation regimens provided twice at 6-monthly intervals for 1 year ( 1996/97 ) . Half the pupils received iron supplementation ( ferrous fumarate 200 mg weekly for 10 weeks ) . Pupils received 2 anthelmintic regimens , either ( i ) albendazole 400 mg plus praziquantel 40 mg/kg or ( ii ) albendazole 400 mg on 3 consecutive days plus praziquantel 40 mg/kg or ( iii ) placebo . Baseline prevalences of Ascaris 55.9 % , Trichuris 83.6 % , hookworm spp . 59.4 % , were reduced after 12 months for single-dose albendazole treatment to Ascaris 17.4 % ( P < 0.005 ) , Trichuris 61.5 % ( NS ) , hookworm spp . 0 % ( P < 0.005 ) , and for triple-dose albendazole treatment to Ascaris 14.8 % ( P < 0.005 ) , Trichuris 25.0 % ( P < 0.01 ) , hookworm 0 % ( P < 0.005 ) . Schistosoma haematobium 43.4 % was reduced among treated groups to 8.3 % ( P < 0.005 ) . There were no significant changes in the anthropometry of the different treatment groups at either 6 or 12 months post treatment . Twelve months after treatment there was a significant increase in haemoglobin levels ( P = 0.02 ) among pupils receiving triple-dose albendazole , praziquantel and ferrous fumarate ; pupils receiving no anthelmintic treatment showed a significant decrease as did pupils who received triple-dose albendazole and praziquantel but no iron . Regular 6-monthly anthelmintic treatment significantly reduced the prevalence of Ascaris , hookworm spp . and S. haematobium infections ( P < 0.05 ) . Triple-dose treatment for Trichuris was significantly more effective than a single dose of albendazole 400 mg ( P = 0.002 ) . In areas with schistosomiasis , hookworm infection and high prevalence of Trichuris infection , combination treatment with praziquantel , triple-dose albendazole , plus iron supplementation , is likely to improve pupils ' health and haemoglobin levels Three hundred forty-one Tanzanian preschool children were r and omly assigned to levamisole or placebo treatment given at three-month intervals . Weights and heights were measured at the tri-monthly treatment visits for a period of one year . Among the 273 children who were seen and weighed at the one-year follow-up visit , the rate of weight gain was 8 per cent greater for those receiving levamisole than for placebo-treated controls ( p = .06 ) . In 78 children known to be infected with Ascaris at baseline , the rate of weight gain was 21 per cent greater in children treated with levamisole than in those receiving placebo ( p = .03 ) . The rate of height gain was no different for treatment and placebo groups A double-blind clinical trial was conducted among 9- to 11-year-old children in sixteen schools in the Chon Buri province of Thail and to assess the effects of an iron supplement combined with an anthelminthic agent ( i.e. albendazole ) . In addition to the albendazole , Fe or placebo tablets were distributed to 2268 children enrolled in grade s three to five without knowledge of the Fe status of the children . Criteria for case inclusion were : ( a ) absence of A E Bart 's or haemoglobin ( Hb ) H disease , ( b ) absence of abnormal Hb EE , and ( c ) age , 108 - 144 months . The results showed a significant improvement in the Fe status of the children after 16 weeks of treatment . The increments were : Hb from 124 to 128 g/l , serum ferritin from 34.54 to 104.72 micrograms/l , transferrin saturation from 24.09 to 35.05 % ; free erythrocyte protoporphyrin decreased from 444.7 to 281.4 micrograms/l erythrocytes . These changes were significantly greater than in the control group that received only the anthelminthic agent . However , the administration of albendazole only also result ed in significant changes in the same Fe indicators Concurrent micronutrient deficiencies are prevalent among Vietnamese school children . A school-based program providing food fortified with multiple micronutrients could be a cost-effective and sustainable strategy to improve health and cognitive function of school children . However , the efficacy of such an intervention may be compromised by the high prevalence of parasitic infestation . To evaluate the efficacy of school-based intervention using multi-micronutrient-fortified biscuits with or without deworming on anemia and micronutrient status in Vietnamese schoolchildren , a r and omized , double-blind , placebo-controlled trial was conducted among 510 primary schoolchildren , aged 6 - 8 y , in rural Vietnam . Albendazole ( Alb ) ( 400 mg ) or placebo was given at baseline . Nonfortified or multi-micronutrient-fortified biscuits including iron ( 6 mg ) , zinc ( 5.6 mg ) , iodine ( 35 microg ) , and vitamin A ( 300 microg retinol equivalents ) were given 5 d/wk for 4 mo . Multi-micronutrient fortification significantly improved the concentrations of hemoglobin ( + 1.87 g/L ; 95 % CI : 0.78 , 2.96 ) , plasma ferritin ( + 7.5 microg/L ; 95 % CI : 2.8 , 12.6 ) , body iron ( + 0.56 mg/kg body weight ; 95 % CI : 0.29 , 0.84 ) , plasma zinc ( + 0.61 micromol/L ; 95 % CI : 0.26 , 0.95 ) , plasma retinol ( + 0.041 micromol/L ; 95 % CI : 0.001 , 0.08 ) , and urinary iodine ( + 22.49 micromol/L ; 95 % CI : 7.68 , 37.31 ) . Fortification reduced the risk of anemia and deficiencies of zinc and iodine by > 40 % . Parasitic infestation did not affect fortification efficacy , whereas fortification significantly enhanced deworming efficacy , with the lowest reinfection rates in children receiving both micronutrients and Alb . Multi-micronutrient fortification of biscuits is an effective strategy to improve the micronutrient status of Vietnamese schoolchildren and enhances effectiveness of deworming Trichuris trichiura is extremely prevalent worldwide and there is concern that this geohelminth may affect the cognitive function of children in developing countries . A r and om-controlled , double-blind , treatment trial was conducted in Jamaican children with light to moderate infections . This was part of a research programme involving several studies in Jamaica . Ninety-seven subjects , each with a minimum of 1200 T. trichiura eggs/g faeces , were r and omly assigned to placebo ( N = 48 ) or treatment ( N = 49 ) groups . Each pair of infected children was matched with an uninfected classmate ( N = 48 ) . All children were given seven cognitive function tests : French-learning ; digit spans ( forwards and backwards ) , Corsi block span ; fluency ; picture search ; and silly sentences . Albendazole was given to the treatment group and the other groups received a placebo . Three months later , these treatments were repeated , and the cognitive function battery was given again . On pre-test , the infected groups performed significantly poorer only in the silly-sentence test ( analysis of variance F-value = 8.17 ; two degrees of freedom ; P < 0.001 ) . There was no significant improvement with treatment in any of the tests . Taking into account these findings and those of the other Jamaican studies , it is therefore probable that light to moderate Trichuris infections have little effect on cognitive functioning in school children who have adequate nutritional status To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Micronutrient deficiencies are associated with impaired growth and cognitive function . A school-based fortification program might benefit schoolchildren but a high prevalence of parasite infestation might affect effectiveness . A r and omized , double-blind , placebo-controlled 2 × 2 factorial trial was conducted to assess the efficacy of multi-micronutrient fortified biscuits with or without de-worming on growth , cognitive function , and parasite load in Vietnamese schoolchildren . Schoolchildren ( n = 510 ) , 6 - 8 years of age were r and omly allocated to receive albendazole or placebo at baseline and four months of multi-micronutrient fortified biscuits ( FB ) or non-fortified biscuits . Children receiving FB for four months scored higher on two cognitive tests : Raven 's Colored Progressive Matrices and the Digit Span Forward test . Children receiving albendazole plus FB had the lowest parasite load after four months . In children receiving FB , mid-upper arm circumference was slightly improved ( + 0.082 cm ) but there were no differences in other indexes of anthropometry . Combining multi-micronutrient fortified biscuits with de-worming is an effective strategy Anemia is common among children in sub-Saharan Africa and its etiology is multifactorial . Likely causes of anemia are low bioavailability of dietary iron , malaria , and helminth infection . In this study , we aim ed to assess the effect of iron fortification , intermittent preventive treatment ( IPT ) of malaria , and anthelmintic treatment on hemoglobin concentration and anemia prevalence among school children . The study was a 6-mo , r and omized , double-blind , controlled trial enrolling 591 6- to 14-y-old school children in Côte d'Ivoire using the following : 1 ) iron-fortified biscuits providing an additional 20 mg iron/d as electrolytic iron 4 times/wk ; 2 ) IPT of malaria with sulfadoxine-pyrimethamine at 0 and 3 mo ; and 3 ) anthelmintic treatment at 0 and 3 mo as the interventions . Prevalence of anemia , iron deficiency , malaria parasitemia , and helminth infection was 70.4 , 9.3 , 57.7 , and 54.8 % , respectively . Iron fortification did not improve iron status , IPT of malaria did not affect malaria burden , and neither had an impact on anemia prevalence . Anthelmintics significantly reduced the burden of helminth infections and decreased anemia prevalence ( odds ratio : 0.4 , 95 % CI : 0.3 , 0.7 ) . The low prevalence of iron deficiency and an extended dry season that decreased malaria transmission likely reduced the potential impact of iron fortification and IPT . In this setting , anthelmintic treatment was the only intervention that modestly decreased rates of anemia We assessed the effectiveness of iron+folic acid for the treatment of severe anemia [ hemoglobin ( Hb ) < 70 g/L ] and the efficacy of added multivitamins and /or anthelminthics among children aged 6 - 24 mo in periurban Karachi , Pakistan . The study design was a double blind , placebo-controlled , r and omized trial of currently recommended daily iron ( 25 mg ) and folic acid ( 100 microg ) for 90 d with daily multivitamins [ vitamin A ( 300 microg , as retinol palmitate ) , vitamin E ( 6 mg tocopherol equivalents ) , vitamin B-12 ( 0.9 microg ) , vitamin C ( 15 mg ) , riboflavin ( 0.5 mg ) ] and /or anthelminthics ( 100 mg mebendazole twice daily for 3 d ) compared with placebos . Treatment response was defined as reaching a Hb concentration > or = 100 g/L at the end of 90 d. The prevalence of severe anemia in the 9518 children screened was 5.7 % and a total of 462 severely anemic children were enrolled in the study . Adherence to treatment was approximately 70 % for iron+folic acid , approximately 80 % for multivitamins , and almost 100 % for mebendazole . Children receiving iron+folic acid alone had a response rate of 38.7 % at 90 d. The additional treatment with mebendazole or multivitamins did not significantly improve cure rates or change the Hb concentration over and above iron+folic acid treatment alone . Adherence to iron+folic acid of higher than the median result ed in a better treatment response rate of 50 % . High-dose daily iron+folic acid performed as well as iron+folic acid with anthelminthics and multivitamins in the treatment of severe anemia in this setting . Higher adherence may be important in enhancing treatment impact |
12,451 | 26,055,135 | ConclusionS PD is associated with reduced morbidity , but equivalent long-term benefits compared to patients undergoing EPD | Introduction The evidence for improved prognostic assessment and long-term survival for extended pancreatoduodenectomy ( EPD ) compared to st and ard pancreatoduodenectomy ( SPD ) in patients with carcinoma of the head of the pancreas has not been considered from only r and omized controlled trials ( RCTs ) .
Methods The aim of this study was to conduct a systematic review and meta- analysis of the outcomes comparing SPD and EPD in RCTs . | Pancreaticoduodenectomy remains the only potentially curative treatment for adenocarcinoma of the pancreas . The aim of this study was to analyze prognostic factors impacting survival after R0 pancreaticoduodenectomy for adenocarcinoma in the head of the pancreas . Between 1995 and 2002 , a potentially curative ( R0 ) pancreaticoduodenectomy with pancreatogastrostomy for ductal adenocarcinoma in the head of the pancreas was performed in 81 patients ( 42 women and 39 men ) with a mean age of 64 years ( range 35–84 ) . Patients were identified from a prospect i ve data base and records were review ed retrospectively . Postoperative mortality was 1 % , and 40 % of patients had complications . Median survival was 18 months , and the 5-year survival was 24 % . Fifteen patients were alive at 5 years . Factors associated with poor survival in multivariate analysis were ( 1 ) two or more positive lymph nodes , ( 2 ) tumor diameter greater than 30 mm , and ( 3 ) age greater than 70 years . In patients with no or with one positive lymph node , the 5-year survival was 44 % . On the other h and , in patients with two or more positive lymph nodes , both the 3- and 5-year survival was 5 % . The main risk factor associated with poor survival after an R0 pancreaticoduodenectomy for adenocarcinoma in the head of pancreas was lymph node status : The presence of two or more positive lymph nodes was associated with decreased survival Objective : To prospect ively evaluate the survival benefit of dissection of the nerve plexus and lymphadenectomy in patients with pancreatic head cancer . Background : Despite r and omized controlled trials on the extent of surgery in pancreatic cancer , attempts have been made to perform more extended resections . Methods : A total of 244 patients were enrolled ; of these , 200 were r and omized to undergo st and ard resection or extended resection , with the latter including the dissection of additional lymph nodes and the right half of the nerve plexus around the superior mesenteric artery and celiac axis . We evaluated 167 patients from 7 centers who fulfilled all of the required criteria . Result : Operation time was longer and estimated blood loss was higher in the extended resection group than in the st and ard resection group , but the R0 resection rate was comparable . The mean number of lymph nodes retrieved per patient was higher in the extended resection group than in the st and ard resection group ( 33.7 vs 17.3 ; P < 0.001 ) . The morbidity rate was slightly higher in the extended resection group than in the st and ard resection group . Two patients in the extended resection group died in hospital . Median survival after R0 resection was similar in the extended resection and st and ard resection groups ( 18.0 vs 19.0 months ; P = 0.239 ) regardless of lymph node metastasis . Adjuvant chemoradiation had a positive impact on overall survival . Conclusions : This study suggests that extended lymphadenectomy with dissection of the nerve plexus does not provide a significant survival benefit compared with st and ard resection in pancreatic head cancer . St and ard resection can be performed safely and efficiently , without negatively affecting oncologic efficacy or long-term survival , when compared with extended pancreaticoduodenal resection . ( NCT00679913 ) Background The value of pancreatoduodenectomy ( PD ) with extended lymphadenectomy for pancreatic cancer has been evaluated by many retrospective studies and 3 r and omized controlled trials ( RCT ) . However , the protocol s used and the results found in the 3 RCTs were diverse . Therefore , a multicenter RCT was proposed in 1998 to evaluate the primary end point of long-term survival and the secondary end points of morbidity , mortality and quality of life of patients undergoing st and ard versus extended lymphadenectomy in radical PD for pancreatic cancer . Methods From March 2000 to May 2003 , 112 patients with potentially curable pancreatic head cancer were enrolled and intraoperatively r and omized to a st and ard or extended lymphadenectomy group . No resected patients received any adjuvant treatments . Results A hundred and one eligible patients were analyzed . Demographic and histopathological characteristics of the two groups were similar . The mean operating time , intraoperative blood loss and number of retrieved lymph nodes were greater in the extended group , but the other operative results were comparable . Conclusions Although this multicenter RCT was conducted in a strict setting , extended lymphadenectomy in radical PD did not benefit long-term survival in patients with resectable pancreatic head cancer and led to levels of morbidity , mortality and quality of life comparable to those found after st and ard lymphadenectomy Objective To evaluate , in a prospect i ve , r and omized single-institution trial , the end points of operative morbidity , operative mortality , and survival in patients undergoing st and ard versus radical ( extended ) pancreaticoduodenectomy . Summary Background Data Numerous retrospective reports and a few prospect i ve r and omized trials have suggested that the performance of an extended lymphadenectomy in association with a pancreaticoduodenal resection may improve survival for patients with pancreatic and other periampullary adenocarcinomas . Methods Between April 1996 and June 2001 , 299 patients with periampullary adenocarcinoma were enrolled in a prospect i ve , r and omized single-institution trial . After intraoperative verification ( by frozen section ) of margin-negative resected periampullary adenocarcinoma , patients were r and omized to either a st and ard pancreaticoduodenectomy ( removing only the peripancreatic lymph nodes en bloc with the specimen ) or a radical ( extended ) pancreaticoduodenectomy ( st and ard resection plus distal gastrectomy and retroperitoneal lymphadenectomy ) . All pathology specimens were review ed , fully categorized , and staged . The postoperative morbidity , mortality , and survival data were analyzed . Results Of the 299 patients r and omized , 5 ( 1.7 % ) were subsequently excluded because their final pathology failed to reveal periampullary adenocarcinoma , leaving 294 patients for analysis ( 146 st and ard vs. 148 radical ) . The two groups were statistically similar with regard to age ( median 67 years ) and gender ( 54 % male ) . All the patients in the radical group underwent distal gastric resection , while 86 % of the patients in the st and ard group underwent pylorus preservation ( P < .0001 ) . The mean operative time in the radical group was 6.4 hours , compared to 5.9 hours in the st and ard group ( P = .002 ) . There were no significant differences between the two groups with respect to intraoperative blood loss , transfusion requirements ( median zero units ) , location of primary tumor ( 57 % pancreatic , 22 % ampullary , 17 % distal bile duct , 3 % duodenal ) , mean tumor size ( 2.6 cm ) , positive lymph node status ( 74 % ) , or positive margin status on final permanent section ( 10 % ) . The mean total number of lymph nodes resected was significantly higher in the radical group . Of the 148 patients in the radical group , only 15 % ( n = 22 ) had metastatic adenocarcinoma in the resected retroperitoneal lymph nodes , and none had retroperitoneal nodes as the only site of lymph node involvement . One patient in the radical group with negative pancreaticoduodenectomy specimen lymph nodes had a micrometastasis to one perigastric lymph node . There were six perioperative deaths ( 4 % ) in the st and ard group versus three perioperative deaths ( 2 % ) in the radical group ( P = NS ) . The overall complication rates were 29 % for the st and ard group versus 43 % for the radical group ( P = .01 ) , with patients in the radical group having significantly higher rates of early delayed gastric emptying and pancreatic fistula and a significantly longer mean postoperative stay . With a mean patient follow-up of 24 months , there were no significant differences in 1- , 3- , or 5-year and median survival when comparing the st and ard and radical groups . Conclusions Radical ( extended ) pancreaticoduodenectomy can be performed with similar mortality but some increased morbidity compared to st and ard pancreaticoduodenectomy . The data to date fail to indicate that a survival benefit is derived from the addition of a distal gastrectomy and retroperitoneal lymphadenectomy to a pylorus-preserving pancreaticoduodenectomy BACKGROUND The role of adjuvant treatment in pancreatic cancer remains uncertain . The European Study Group for Pancreatic Cancer ( ESPAC ) assessed the roles of chemoradiotherapy and chemotherapy in a r and omised study . METHODS After resection , patients were r and omly assigned to adjuvant chemoradiotherapy ( 20 Gy in ten daily fractions over 2 weeks with 500 mg/m(2 ) fluorouracil intravenously on days 1 - 3 , repeated after 2 weeks ) or chemotherapy ( intravenous fluorouracil 425 mg/m(2 ) and folinic acid 20 mg/m(2 ) daily for 5 days , monthly for 6 months ) . Clinicians could r and omise patients into a two-by-two factorial design ( observation , chemoradiotherapy alone , chemotherapy alone , or both ) or into one of the main treatment comparisons ( chemoradiotherapy versus no chemoradiotherapy or chemotherapy versus no chemotherapy ) . The primary endpoint was death , and all analyses were by intention to treat . Findings 541 eligible patients with pancreatic ductal adenocarcinoma were r and omised : 285 in the two-by-two factorial design ( 70 chemoradiotherapy , 74 chemotherapy , 72 both , 69 observation ) ; a further 68 patients were r and omly assigned chemoradiotherapy or no chemoradiotherapy and 188 chemotherapy or no chemotherapy . Median follow-up of the 227 ( 42 % ) patients still alive was 10 months ( range 0 - 62 ) . Overall results showed no benefit for adjuvant chemoradiotherapy ( median survival 15.5 months in 175 patients with chemoradiotherapy vs 16.1 months in 178 patients without ; hazard ratio 1.18 [ 95 % CI 0.90 - 1.55 ] , p=0.24 ) . There was evidence of a survival benefit for adjuvant chemotherapy ( median survival 19.7 months in 238 patients with chemotherapy vs 14.0 months in 235 patients without ; hazard ratio 0.66 [ 0.52 - 0.83 ] , p=0.0005 ) . Interpretation This study showed no survival benefit for adjuvant chemoradiotherapy but revealed a potential benefit for adjuvant chemotherapy , justifying further r and omised controlled trials of adjuvant chemotherapy in pancreatic cancer Due to uncertainties regarding clinical ly meaningful gains from adjuvant chemotherapy after colorectal cancer surgery , several Nordic Groups in the early 1990s initiated r and omised trials to prove or reject such gains . This report gives the joint analyses after a minimum 5-year follow-up . Between October 1991 and December 1997 , 2 224 patients under 76 years of age with colorectal cancer stages II and III were r and omised to surgery alone ( n = 1 121 ) or adjuvant chemotherapy ( n = 1 103 ) which varied between trials ( 5FU/levamisole for 12 months , n = 444 ; 5FU/leucovorin for 4 - 5 months according to either a modified Mayo Clinic schedule ( n = 262 ) or the Nordic schedule ( n = 397 ) . Some centres also r and omised patients treated with 5FU/leucovorin to+/-levamisole ) . A total of 812 patients had colon cancer stage II , 708 colon cancer stage III , 323 rectal cancer stage II and 368 rectal cancer stage III . All analyses were according to intention-to-treat . No statistically significant difference in overall survival , stratified for country or region , could be found in any group of patients according to stage or site . In colon cancer stage III , an absolute difference of 7 % ( p = 0.15 ) , favouring chemotherapy , was seen . The present analyses corroborate a small but clinical ly meaningful survival gain from adjuvant chemotherapy in colon cancer stage III , but not in the other presentations BACKGROUND To compare operative morbidity , mortality , quality of life , and survival after pancreatoduodenectomy ( PD ) versus pancreatoduodenectomy with extended lymphadenectomy ( PD/ELND ) in patients with resectable pancreatic cancer . METHODS From May 1997 to July 2003 there were 132 patients with biopsy examination-proven or suspected adenocarcinoma of the pancreatic head who agreed to participate in a single-institution , prospect i ve , r and omized trial . If resectable at operation , patients then were r and omized to st and ard PD ( 40 patients ) or PD/ELND ( 39 patients ) . Quality of life was assessed by using the Functional Assessment of Response to Cancer Therapy specific to the pancreas . Morbidity , mortality , and survival were analyzed . RESULTS Demographics and pathologic characteristics for both groups were similar . When comparing PD/ELND with st and ard PD , the median operating time was greater for the PD/ELND group ( 7.6 h vs 6.2 h , P < .01 ) , blood transfusion more likely ( 44 % vs 22 % , P < .05 ) , and the median number of lymph nodes resected was greater ( 36 vs 15 nodes , P < .01 ) . Morbidity and mortality rates were comparable . Median duration s of stay were 11 and 10.5 days ( P = NS ) , respectively . There were no significant differences in 1-year ( 71 % vs 82 % ) , 3-year ( 25 % vs 41 % ) , 5-year ( 16.5 % vs 16.4 % ) , and median ( 19 vs 26 mo ) survival ( P = .32 ) . At 4 months postoperatively , diarrhea , body appearance , and bowel control scored lower on the Functional Assessment of Response to Cancer Therapy specific to the pancreas after PD/ELND ( P < .05 ) . CONCLUSIONS Although a much larger study would have more power to compare statistically the survival between groups , both the decrement in quality of life and similar studies showing no survival difference make PD/ELND unattractive for further prospect i ve investigation BACKGROUND The effect of adjuvant treatment on survival in pancreatic cancer is unclear . We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and up date the interim results . METHODS In a multicenter trial using a two-by-two factorial design , we r and omly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone ( 20 Gy over a two-week period plus fluorouracil ) , 75 patients to chemotherapy alone ( fluorouracil ) , 72 patients to both chemoradiotherapy and chemotherapy , and 69 patients to observation . RESULTS The analysis was based on 237 deaths among the 289 patients ( 82 percent ) and a median follow-up of 47 months ( interquartile range , 33 to 62 ) . The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy ( P=0.05 ) . The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy ( P=0.009 ) . The benefit of chemotherapy persisted after adjustment for major prognostic factors . CONCLUSIONS Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer , whereas adjuvant chemoradiotherapy has a deleterious effect on survival OBJECTIVE The study was conducted to determine whether the performance of an extended lymphadenectomy and retroperitoneal soft-tissue clearance in association with a pancreatoduodenal resection improves the long-term survival of patients with a potentially curable adenocarcinoma of the head of the pancreas . SUMMARY BACKGROUND DATA The usefulness of performing an extended lymphadenectomy and retroperitoneal soft-tissue clearance in conjunction with a pancreatoduodenal resection in the treatment of ductal adenocarcinoma of the head of the pancreas is still unknown . Published studies suggest a benefit for the procedure in terms of better long-term survival rates ; however , these studies were retrospective or did not prospect ively evaluate large series of patients . MATERIAL S AND METHODS Eighty-one patients undergoing a pancreatoduodenal resection for a potentially curable ductal adenocarcinoma of the head of the pancreas were r and omized to a st and ard ( n = 40 ) or extended ( n = 41 ) lymphadenectomy and retroperitoneal soft-tissue clearance in a prospect i ve , multicentric study . The st and ard lymphadenectomy included removal of the anterior and posterior pancreatoduodenal , pyloric , and biliary duct , superior and inferior pancreatic head , and body lymph node stations . In addition to the above , the extended lymphadenectomy included removal of lymph nodes from the hepatic hilum and along the aorta from the diaphragmatic hiatus to the inferior mesenteric artery and laterally to both renal hila , with circumferential clearance of the origin of the celiac trunk and superior mesenteric artery . Patients did not receive any postoperative adjuvant therapy . RESULTS Demographic ( age , gender ) and histopathologic ( tumor size , stage , differentiation , oncologic clearance ) characteristics were similar in the two patient groups . Performance of the extended lymphadenectomy added time to the procedure , although the difference did not reach statistical significance ( 397 + /- 50 minutes vs. 372 + /- 50 minutes , p > 0.05 ) . Transfusion requirements , postoperative morbidity and mortality rates , and overall survival did not differ between the two groups . When subgroups of patients were analyzed , using an a posteriori analysis that was not planned at the time of study design , there was a significantly ( p < 0.05 ) longer survival rate in node positive patients after an extended rather than a st and ard lymphadenectomy . The survival curve of node positive patients after an extended lymphadenectomy could be superimposed onto the curves of node negative patients . Survival curves in node negative patients did not differ according to the magnitude of the lymphadenectomy . Multivariate analysis of all patients showed that long-term survival was affected by tumor differentiation ( well vs. moderately vs. poorly differentiated , p > 0.001 ) , diameter ( < or = 2.0 cm . vs. > 2.0 cm . , p < 0.01 ) , lymph node metastasis ( absent vs. present , p < 0.01 ) and need for 4 or more units of transfused blood ( < 4 vs. > or = 4 , p < 0.01 ) . CONCLUSIONS The addition of an extended lymphadenectomy and retroperitoneal soft-tissue clearance to a pancreatoduodenal resection does not significantly increase morbidity and mortality rates . Although the overall survival rate does not differ in the two groups , there appears to be a trend toward longer survival in node positive patients treated with an extended rather than a st and ard lymphadenectomy OBJECTIVE This prospect i ve , r and omized , single-institution trial was design ed to evaluate the end points of mortality , morbidity , and survival in patients undergoing st and ard versus radical ( extended ) pancreaticoduodenectomy ( including distal gastrectomy and retroperitoneal lymphadenectomy ) . SUMMARY BACKGROUND DATA Numerous retrospective reports and one prospect i ve r and omized trial have suggested that the performance of an extended lymphadenectomy in association with a pancreaticoduodenal resection may improve long-term survival for some patients with pancreatic and other periampullary adenocarcinomas . Many of these previously published studies can be criticized for their retrospective and nonr and omized design s , for the inclusion of nonconcurrent control groups , and for their small numbers . METHODS Between April 1996 and December 1997 , 114 patients with periampullary adenocarcinoma were enrolled in an ongoing , prospect i ve , r and omized trial at The Johns Hopkins Hospital . After intraoperative verification of completely resected periampullary adenocarcinoma , the patients were r and omized to receive either a st and ard pancreaticoduodenectomy ( removing only the peripancreatic lymph nodes en bloc with the specimen ) or a radical pancreaticoduodenectomy ( st and ard resection plus distal gastrectomy and retroperitoneal lymphadenectomy ) . All pathology specimens were review ed and categorized . The postoperative morbidity , mortality , and short-term outcomes were examined . RESULTS Of the 114 patients r and omized , 56 underwent a st and ard pancreaticoduodenectomy and 58 a radical pancreaticoduodenectomy . The two groups were statistically similar with regard to age and gender , but there was a higher percentage of white patients in the radical group . All the patients in the radical group underwent distal gastric resection , whereas 86 % of the patients in the st and ard group underwent pylorus preservation . The mean operative time in the radical group was 6.8 hours , compared with 6.2 hours in the st and ard group . There were no significant differences between the two groups with respect to the intraoperative blood loss , transfusion requirements , location of primary tumor , mean tumor size , positive lymph node status , or positive margin status . There were three deaths in the st and ard group and two in the radical group . The complication rates were 34 % for the st and ard group and 40 % for the radical group . Patients undergoing radical resection had a higher incidence of early delayed gastric emptying but had similar rates of other complications , such as pancreatic fistula , wound infection , intraabdominal abscess , and need for reoperation . The mean total number of lymph nodes resected was higher in the radical group . Of the 58 patients in the radical group , only 10 % had metastatic carcinoma in the resected retroperitoneal lymph nodes , and none of those patients had the retroperitoneal nodes as the only site of lymph node involvement . The 1-year actuarial survival rate for patients surviving the immediate postoperative periods was 77 % for the st and ard resection group and 83 % for the radical resection group . CONCLUSIONS These data demonstrate that radical pancreaticoduodenectomy ( with the addition of a distal gastrectomy and extended retroperitoneal lymphadenectomy to a st and ard pancreaticoduodenectomy ) can be performed with similar morbidity and mortality to st and ard pancreaticoduodenectomy . However , the survival data are not sufficiently mature and the numbers of patients enrolled are not adequate to allow firm conclusions to be drawn regarding survival benefit Mortality rates associated with pancreatic resection for cancer have steadily decreased with time , but improvements in long‐term survival are less clear . This prospect i ve study evaluated risk factors for survival after resection for pancreatic adenocarcinoma |
12,452 | 29,105,728 | There is very limited data in the literature to ascertain the accuracy of tests for detecting strabismus in the community as performed by non-expert screeners . | BACKGROUND Strabismus ( misalignment of the eyes ) is a risk factor for impaired visual development both of visual acuity and of stereopsis .
Detection of strabismus in the community by non-expert examiners may be performed using a number of different index tests that include direct measures of misalignment ( corneal or fundus reflex tests ) , or indirect measures such as stereopsis and visual acuity .
The reference test to detect strabismus by trained professionals is the cover‒uncover test .
OBJECTIVES To assess and compare the accuracy of tests , alone or in combination , for detection of strabismus in children aged 1 to 6 years , in a community setting by non-expert screeners or primary care professionals to inform healthcare commissioners setting up childhood screening programmes .
Secondary objectives were to investigate sources of heterogeneity of diagnostic accuracy . | OBJECTIVE To compare the ability of pediatric residents to differentiate an asymmetric from a symmetric red reflex in patients with anisometropia and microstrabismus using the Brückner reflex and the Medical Technology Innovations ( MTI ) photoscreener . METHODS A prospect i ve , masked , case-control study was performed . Twelve pediatric residents evaluated 10 study patients and 6 control subjects in a masked manner in 2 separate sessions , using the Brückner reflex or the MTI photoscreener , evaluating for asymmetric ( abnormal ) or symmetric ( normal ) red reflexes between the 2 eyes . Each study patient had asymmetric red reflexes and the amblyogenic risk factor of anisometropia or microstrabismus . Each control subject had symmetric red reflexes . RESULTS The pediatric residents had a mean correct score of 82 % ( 69%-100 % ) using the MTI photoscreener versus a mean correct score of 65 % ( 44%-81 % ) using the Brückner reflex ( McNemar test : alpha < 0.01 ) . The sensitivity of the MTI photoscreener evaluation was 89 % in comparison to 61 % for the Brückner reflex . The specificities for the MTI photoscreener versus the Brückner reflex were similar at 69 % and 71 % , respectively . CONCLUSIONS Pediatric residents were better at detecting asymmetric red reflexes in patients with anisometropia and microstrabismus when evaluating MTI photoscreener photographs than when evaluating the red reflexes by the Brückner reflex . The MTI photoscreener may be a more sensitive method than the Brückner reflex to screen for the common amblyogenic risk factors of anisometropia and microstrabismus by easier detection of red reflex asymmetry PURPOSE To evaluate the diagnostic accuracy of the plusoptiX S04 digital photoscreener in a school screening program . METHODS Between 2006 and 2007 , 1343 information pamphlets/consent forms were sent to all junior kindergarten students in a local school district . Assistants from a local public health unit photographed 307 children . Of these , 271 children received an independent ophthalmic examination by a physician . Photographic results were compared with the those of the ophthalmic examination . Amblyopia risk factors were defined as anisometropia > 1 D ( sphere or cylinder ) , astigmatism > 1.25 D , myopia > 3 D , hyperopia > 3.5 D , any manifest strabismus , and any media opacity . RESULTS Photographic and examination results agreed in 94 % of cases . Sensitivity in detecting amblyopia risk factors was 83 % ; specificity was 95 % . The positive and negative predictive values were 73 % and 97 % , respectively . The untestable/unusable rate was 1 % . CONCLUSIONS These results compare favorably with a previously reported ( but no longer available ) digital photoscreening camera and are superior to results obtained with other off-axis photoscreening devices that require human interpretation . On the basis of these results , in a real-world screening program , the camera would falsely refer 4 % of those screened and would fail to correctly refer 2 % . The accuracy of the plusoptiX S04 camera in detecting amblyopia risk factors appears sufficiently high to consider its further deployment in a widespread school screening program Aim To evaluate the efficacy of the three-dimensional ( 3D ) Strabismus Photo Analyzer for estimating binocular alignment using photographs . Methods Thirty-two subjects with exotropia , 30 subjects with esotropia and 38 orthotropic subjects were included . Two independent ophthalmologists examined the angle of deviation using the Krimsky test and prism and alternate cover test ( PCT ) . Full-face photographs were obtained using an 8.2-megapixel digital single-lens reflex camera , and the images were analysed using the 3D Strabismus Photo Analyzer . The images were adjusted for age-dependent ophthalmic biometry and angle κ . The main outcome measures were inter-observer variability , test‐retest reliability and correlation between the angles of deviation measured by different methods . Results The 95 % limit of agreement of inter-observer variability was ±3.5 ° ( 6.1 prism dioptres ( PD ) ) , ±3.1 ° ( 5.4 PD ) and ±1.5 ° ( 2.6 PD ) for the Krimsky test , PCT and the 3D Strabismus Photo Analyzer , respectively . The test‐retest reliability was ±2.8 ° ( 4.9 PD ) for the 3D Strabismus Photo Analyzer versus the Krimsky test . The results of the Krimsky test and 3D Strabismus Photo Analyzer showed a strong positive correlation . Conclusions The 3D Strabismus Photo Analyzer is a simple and reliable tool for measuring ocular deviation . It has excellent agreement with the Krimsky test and substantially improved reproducibility The primate visual cortex , including that of man , receives separate input from each eye and these interact in binocular cortical neurones . This organization is known to be vulnerable to disruption in early life1 . To underst and the development of human visual cortex , and to detect and assess disorders of binocular function at the earliest possible age , a robust method is needed for detecting binocular interactions in the infant 's visual system . We have done this by recording cortical visual evoked responses ( VERs ) to the onset and offset of binocular correlation in a large-screen dynamic r and om dot display . We report here that , in general , the human infant has a functional binocular visual cortex by 3 months of age , with some individuals showing cortical binocularity at an earlier age A Cochrane review of literature from 1966 to 2004 on screening for correctable visual acuity defects in school-aged children and adolescents found “ no robust trials available that allow the benefits of school vision screening to be measured . The disadvantage of attending school with a visual acuity deficit also needs to be quantified . The impact of a screening program will depend on the geographical , and the socio-economic setting in which it is conducted ” [ 2 ] . However , major refractive errors can occur in 5 % to 7 % of preschoolers [3][4 ] ; individual r and omized , longitudinal studies report that early screening has been associated with a decrease in the prevalence of amblyopia and improved acuity by 60 % [ 5 ] . Screening before three years of age is associated with a 70 % lower prevalence of amblyopia after treatment [4][6 ] . The single and most effective test for amblyopia is the determination of visual acuity by noninvasive testing . A Cochrane review on screening specifically for amblyopia ( 1966 to 2005 ) concluded that “ the lack of data from r and omized controlled trials makes it difficult to analyze the impact of screening programs on the prevalence of amblyopia . The absence of such evidence can not be taken to mean that vision screening is not beneficial ; simply that this intervention has not yet been tested in robust studies ” [ 7 ] . Adverse effects on educational and social development , as well as limitations to career choice are obvious consequences of poor visual acuity . Uncorrected amblyopia is a significant risk factor for total blindness , in the case of injury or disease , in the better functioning eye . The American Academy of Ophthalmology and the American Academy of Pediatrics [ 6 ] recommend visual assessment from birth and at all routine health supervisory visits . The child ’s anatomy and function should be checked at regular infant and well-child visits , and visual acuity should be assessed at the preschool stage as well as when there is a complaint . Infants with a known risk ( retinopathy of prematurity , Down ’s syndrome , etc ) or significant family history ( congenital glaucoma , strabismus ) should be referred for further evaluation [ 6 ] PURPOSE To compare 11 preschool vision screening tests administered by licensed eye care professionals ( LEPs ; optometrists and pediatric ophthalmologists ) . DESIGN Multicenter , cross-sectional study . PARTICIPANTS A sample ( N = 2588 ) of 3- to 5-year-old children enrolled in Head Start was selected to over-represent children with vision problems . METHODS Certified LEPs administered 11 commonly used or commercially available screening tests . Results from a st and ardized comprehensive eye examination were used to classify children with respect to 4 targeted conditions : amblyopia , strabismus , significant refractive error , and unexplained reduced visual acuity ( VA ) . MAIN OUTCOME MEASURES Sensitivity for detecting children with > or = 1 targeted conditions at selected levels of specificity was the primary outcome measure . Sensitivity also was calculated for detecting conditions grouped into 3 levels of importance . RESULTS At 90 % specificity , sensitivities of noncycloplegic retinoscopy ( NCR ) ( 64 % ) , the Retinomax Autorefractor ( 63 % ) , SureSight Vision Screener ( 63 % ) , and Lea Symbols test ( 61 % ) were similar . Sensitivities of the Power Refractor II ( 54 % ) and HOTV VA test ( 54 % ) were similar to each other . Sensitivities of the R and om Dot E stereoacuity ( 42 % ) and Stereo Smile II ( 44 % ) tests were similar to each other and lower ( P<0.0001 ) than the sensitivities of NCR , the 2 autorefractors , and the Lea Symbols test . The cover-uncover test had very low sensitivity ( 16 % ) but very high specificity ( 98 % ) . Sensitivity for conditions considered the most important to detect was 80 % to 90 % for the 2 autorefractors and NCR . Central interpretations for the MTI and iScreen photoscreeners each yielded 94 % specificity and 37 % sensitivity . At 94 % specificity , the sensitivities were significantly better for NCR , the 2 autorefractors , and the Lea Symbols VA test than for the 2 photoscreeners for detecting > or = 1 targeted conditions and for detecting the most important conditions . CONCLUSIONS Screening tests administered by LEPs vary widely in performance . With 90 % specificity , the best tests detected only two thirds of children having > or = 1 targeted conditions , but nearly 90 % of children with the most important conditions . The 2 tests that use static photorefractive technology were less accurate than 3 tests that assess refractive error in other ways . These results have important implication s for screening preschool-aged children Stereoscopic depth perception was tested in human infants by a new method based on attracting the infant 's attention through movement of a stereoscopic contour formed from a dynamic r and om-element stereogram . The results reveal that stereopsis emerges at 3 1/2 to 6 months of age , an outcome consistent with evidence for rapid postnatal development of the visual system PURPOSE To assess the accuracy of the Lang II stereotest in screening for strabismus , amblyopia , and anisometropia in 6-year-old children . DESIGN Cross-sectional population -based study . METHODS The Sydney Myopia Study examined 1765 6-year-old children ( 78.9 % of eligible ) who were identified by r and om cluster sampling of 34 schools in Sydney , Australia . Sensitivity and specificity of the Lang II stereotest was determined by best stereoacuity . Cycloplegic autorefraction , assessment of visual acuity , and ocular motility were conducted . RESULTS Test sensitivity ranged from 21.4 % for anisometropia ( > or = 1.0 diopter ) to 31.3 % for amblyopia . The detection rate for new cases of amblyopia ranged from 20 % to 40 % ; the detection rate for new cases of strabismus was 30 % . Specificity was > 98 % in all three conditions . Children with false-negative results included newly diagnosed cases of strabismus ( 14 of 25 children ) or amblyopia ( 5 of 12 children ) . CONCLUSION The Lang II stereotest , when used alone , has very limited value as a screening test of binocular dysfunction Purpose To determine the efficacy of distance stereotesting as a screening device . Methods Distance stereoacuity using the global R and om Dot and contour Circle test of the Mentor BVAT II-SG computerized testing system was measured for 216 patients , ages 6 to 18 years , before the clinical examination . Patients were classified into pass/fail groups in the areas of refractive error change ( REC ) , ocular deviation ( DEV ) , visual acuity ( VA ) , and all three together ( EXAM ) . Legitimate cutoff scores were obtained when patients were classified as ‘ pass ’ as follows : REC if the change was 0.50 D or less in sphere or cylinder relative to the habitual correction or to emmetropia if no habitual correction ; DEV if there was no heterophoria or strabismus at distance ( criteria of heterophoria of < 6 prism diopters and heterophorias of any magnitude were also tested ) ; VA if the acuity at distance was better than or equal to 20/25 in the poorer eye and better than or equal to 20/20 in the better eye ; EXAM if they were pass in REC , DEV , and VA . Optimal pass/fail cutoff values for the stereopsis measurements were determined by finding the maximum & khgr;2 value from contingency tables constructed using pass/fail levels for the screening test at each of the observed levels . Results The pass rates for REC , DEV , VA , and EXAM were 45 % , 72 % , 42 % , and 24 % , respectively . Patients passed the BVAT at the analytically determined optimal cutoff values of less than or equal to 120 sec arc for global and less than or equal to 30 sec arc for contour stereopsis . The sensitivity and specificity for global stereopsis were 0.90 and 0.40 for REC , 0.89 and 0.30 for DEV , 0.93 and 0.51 for VA , and 0.87 and 0.63 for EXAM . For contour stereopsis , the corresponding values were 0.85 and 0.42 , 0.89 and 0.34 , 0.91 and 0.53 , and 0.84 and 0.62 . Conclusion Distance stereotesting is highly sensitive to small refractive error changes , heterophorias and strabismus , visual acuities < 20/25 , or any of the three . Global stereopsis is only slightly better than contour stereopsis at classifying patients . Distance stereotesting has potential as an effective screening test Purpose To investigate the development of stereoscopic acuity ( stereoacuity ) in children longitudinally . Methods Seven full-term normal infants whose age at the beginning of the study was between 12 and 23 weeks were studied . A computer-based r and om-dot test of stereoscopic vision ( TV-R and om Dot Stereo Test ) was used to measure stereoacuity . The test was repeated at 2- to 3-month intervals until the children reached 2 years of age , and then every 6 to 12 months until they reached 5 years of age . Results All of the infants were found to have a stereoacuity of 2480 seconds of arc ( 2480″ ) with this test by 26 weeks of age . The first reliable measurement of stereoacuity was obtained from a 16-week-old infant . Stereoacuity did not improve significantly between 6 and 12 months , but it improved rapidly after 12 months . All children had a stereoacuity of 100″ with the Titmus Stereo Tests at 5 years of age , but the best stereoacuity with the TV-R and om Dot Stereo Test was 229″ at 28.9 months . Conclusions The development of stereoacuity studied longitudinally was similar to that obtained by cross-sectional studies . The TV-R and om Dot Stereo Test is a useful program for measuring stereopsis in preverbal children . Jpn J Ophthalmol 2005;49:1–5 © Japanese Ophthalmological Society BACKGROUND It has been suggested that a decrease in distance stereoacuity in patients with intermittent exotropia is a good indicator of diminishing control . However , there has been no adequate explanation for this reported reduction in distance stereoacuity in these patients . We postulate that the decrease in stereoacuity is related to blurred visual acuity created by an increasing dem and on accommodation , which these patients use in an attempt to control the exodeviation . This can best be assessed by measuring binocular visual acuity ( BVA ) . Analysis of BVA could provide a useful clinical tool to evaluate control measures used by patients with intermittent exotropia . METHODS A prospect i ve study of patients with intermittent exotropia , ranging in age from 6 to 60 years , was performed . Only those patients with the presence of either basic or divergence excess ( simulated or true ) type exodeviation were included in the study . The data analysis included the age of these patients , age at onset of the deviation , monocular and binocular visual acuity , oculomotor and fusional status , and near and distance stereoacuity . RESULTS Data from 36 patients show that the measurements of BVA correlated well with a corresponding loss of distance stereoacuity but not with the size of the deviation . CONCLUSION The decrease of stereoacuity reported in patients with exotropia can be explained by increased accommodation and decreased distance BVA . This measurement can be a simple method of quantifying the fusional control of patients with intermittent exotropia PURPOSE Distance stereoacuity is used to monitor deterioration of intermittent exotropia ( IXT ) , but variability of stereoacuity has not been studied rigorously . The purpose of this study was to assess the variability of stereoacuity over one day in children with IXT . DESIGN Prospect i ve cohort study . METHODS Twelve children with IXT were recruited . Stereoacuity was assessed using the Frisby Davis Distance test and the Distance R and ot test at distance , and the Frisby and Preschool R and ot tests at near . Tests were repeated three or four times over the day , with at least two hours between assessment s. The main outcome measure was variable stereoacuity defined as a change by two or more log levels between any two time points over the day . RESULTS Variable stereoacuity at distance was found in five ( 42 % ) of 12 patients . Four ( 33 % ) of 12 patients demonstrated variable results using the Distance R and ot test , three of whom also showed variable results using the Frisby Davis Distance test . One patient had variable results using the Frisby Davis Distance test only . Nine ( 75 % ) of 12 patients completed near stereoacuity testing ; two ( 22 % ) of nine showed variable near stereoacuity . Two ( 22 % ) of nine showed variable results using the Preschool R and ot test , one ( 11 % ) of whom also had variable results using the Frisby test . In some cases , stereoacuity changed from measurable stereoacuity on one assessment to nil on another . CONCLUSIONS Nearly half of children with IXT show marked changes in stereoacuity over the course of a single day . When based on isolated measures , an apparent change in distance stereoacuity between visits should be interpreted with caution Demonstrating stereopsis is valuable in vision screening of infants and toddlers , since its presence rules out the possibility of profound visual deficits . We assessed the performance of 55 infants and young children on three clinical ly available tests , the Lang , the Frisby and the TNO . The results were compared with those found using a computerized dynamic r and om dot stereogram . Most of the children tested were under 3 years of age and 10 were aged under 1 year . The Lang test was passed by 74 % , including 50 % of those under 1 year . The Frisby test was passed by 65 % , but by only 20 % of infants under 1 year . Forty-nine per cent passed the TNO test ; none were under 1 year . The computerized stereogram was passed by 42.5 % of those tested , including 100 % of those over 3 years old . Both this test and the TNO presented difficulty in testing infants between 8 months and 2 years because of the increased likelihood that these children would reject the red/green glasses . We recommend that the most appropriate stereotest is largely based on whether the child will tolerate red/green glasses . We would use the dynamic r and om dot test for infants under 8 months of age , the Lang or Frisby stereotest for infants from 8 months to 30 months , and the TNO or dynamic r and om dot stereogram after this age PURPOSE To compare the performance of nurse screeners with that of lay screeners in administering preschool vision screening tests . METHODS Trained nurse and lay screeners administered the Retinomax Autorefractor ( Right Manufacturing , Virginia Beach , VA ) , SureSight Vision Screener ( Welch Allyn , Inc. , Skaneateles Falls , NY ) , crowded Linear Lea Symbols visual acuity ( VA ) test at 10 ft ( Precision Vision , Inc. , La Salle , IL ) , and Stereo Smile II test ( Stereo Optical , Inc. , Chicago , IL ) to 3- to 5-year-old Head Start participants . Lay screeners also administered a crowded Single Lea Symbols VA test at 5 ft ( Good-Lite , Inc. ) . Screening results were compared with the classification of the children according to the presence of one or more of four conditions ( amblyopia , strabismus , significant refractive error , and unexplained reduced VA ) based on the results of a gold st and ard eye examination by study -certified optometrists and ophthalmologists . The primary outcome measure was sensitivity for detecting children with one or more targeted conditions at 0.90 specificity . RESULTS Nurse screeners achieved slightly higher sensitivities with the Retinomax , SureSight , and Stereo Smile II tests than did lay screeners ; however , most differences were small and not statistically significant . Nurse screeners achieved significantly higher sensitivity with the Linear Lea Symbols VA test than did lay screeners . Lay screeners achieved strikingly higher sensitivity with the Single Lea Symbols VA test than did nurse or lay screeners using the Linear Lea Symbols VA test . Combining the Stereo Smile II test with each of the other tests did not result in improved sensitivities for detecting one or more targeted conditions . CONCLUSIONS Nurse and lay screeners can achieve similar sensitivity , when specificity is set at 0.90 , for detecting preschool children in need of a comprehensive eye examination PURPOSE To define the critical period for susceptibility of human stereopsis to an anomalous binocular visual experience . METHODS R and om dot stereoacuity was measured in 152 children with a history of onset of either infantile or accommodative strabismus before 5 years of age . In each of these population s and in the combined population , the critical periods for susceptibility of stereopsis are described using four-parameter developmental weighting functions . RESULTS In children with infantile strabismus , the critical period for susceptibility of stereopsis begins at 2.4 months and peaks at 4.3 months . In children with accommodative esotropia , the critical period for susceptibility of stereopsis begins at 10.8 months and peaks at 20 months . When the data are combined across the two population s , the critical period begins soon after birth and peaks sharply at 3.5 months but shows continued susceptibility to at least 4.6 years . CONCLUSIONS An anomalous binocular visual experience during early infancy severely disrupts stereopsis , yet the critical period for susceptibility of stereopsis extends through late infancy and early childhood and continues to at least 4.6 years of age PURPOSE To assess the suitability of Brückner test as a screening test to detect significant refractive errors in children . MATERIAL S AND METHODS A pediatric ophthalmologist prospect ively observed the size and location of pupillary crescent on Brückner test as hyperopic , myopic or astigmatic . This was compared with the cycloplegic refraction . Detailed ophthalmic examination was done for all . Sensitivity , specificity , positive predictive value and negative predictive value of Brückner test were determined for the defined cutoff levels of ametropia . RESULTS Ninety-six subjects were examined . Mean age was 8.6 years ( range 1 to 16 years ) . Brückner test could be completed for all ; the time taken to complete this test was 10 seconds per subject . The ophthalmologist identified 131 eyes as ametropic , 61 as emmetropic . The Brückner test had sensitivity 91 % , specificity 72.8 % , positive predictive value 85.5 % and negative predictive value 83.6 % . Of 10 false negatives four had compound hypermetropic astigmatism and three had myopia . CONCLUSIONS Brückner test can be used to rapidly screen the children for significant refractive errors . The potential benefits from such use may be maximized if programs use the test with lower crescent measurement cutoffs , a crescent measurement ruler and a distance fixation target PURPOSE To develop a presentation protocol for the new Frisby-Davis 2 ( FD2 ) distance stereoacuity test . DESIGN Prospect i ve data collection . METHODS Stereoacuity was tested monocularly and binocularly in 95 patients with a variety of strabismic and nonstrabismic conditions , using the FD2 , employing a modified staircase procedure . The Preschool R and ot Stereoacuity test and the near Frisby test were used to determine whether a patient was stereoblind . RESULTS Under monocular conditions , 35 ( 37 % ) of 95 patients passed at least the largest disparity of the FD2 indicating a problem with monocular cues . The binocular protocol was then modified to include a monocular test phase . Using the new protocol , if a patient could achieve the same stereoacuity under monocular and binocular conditions , they were deemed to have no stereopsis . Testing 28 additional stereoblind patients using the new modified protocol revealed no false positives . CONCLUSION The FD2 stereotest is a useful measure of distance stereoacuity , provided the presentation protocol accounts for monocular cues Dynamic r and om-dot stereograms and correlograms were used to elicit visually evoked brain potentials from human infants , and these potentials were compared with potentials evoked by classical checkerboard pattern reversal . The results indicate that infants begin to produce stereoscopically evoked potentials at the age of 10 to 19 weeks , several weeks after showing classical checkerboard-evoked potentials , and suggest that the onset of cortical binocularity precedes stereopsis PURPOSE Two preliterate acuity charts , the Lea Symbol chart and the HOTV chart , were compared prospect ively in an established preschool vision screening program . The charts were compared by measuring time required to test , reliability coefficients , and the percentage of children testable with each chart . METHODS AND MATERIAL S Seven hundred and seventy-seven 3- to 5-year-old children were r and omized to four screening sequences that determined the order of chart use . Each child was screened on two occasions within 6 weeks . Testing was performed at 10 feet , and optotypes were not isolated for testing . RESULTS Mean test time was significantly less for older children , but was not related to the chart used . Reliability coefficients were similar for the Lea Symbols and the HOTV charts . The percentage of children testable by each chart improved with increased age of the child . More 3 year olds were testable with the Lea Symbols chart compared to the HOTV chart ( 92 % versus 85 % , P = .05 ) . CONCLUSIONS Vision screening with either chart was more rapid and more frequently achieved with 4- and 5-year-old children compared with the 3 year olds . For the population as a whole , each chart gave similar results . Among the 3 year olds , however , testability rates were better for the Lea Symbols chart . The Lea Symbols chart is an acceptable option for preschool vision screening , and may be more efficacious than the HOTV chart for screening 3-year-old children PURPOSE This study estimates the prevalence of common visual disorders ( amblyopia , strabismus , refractive errors ) in a group of inner-city school children . In addition , the study addresses the issue of access to care for vision-screening programs , specifically for children with recognized difficulties in obtaining routine medical care . METHODS School children from an inner-city elementary school were enrolled into a prospect i ve vision-screening program combining the identification arm ( screening ) and diagnostic/treatment arm ( ophthalmic examination ) . The screening consisted of Snellen E optotypes presented at a 10-foot test distance . Each child failing the vision screening was examined by an ophthalmologist at the school using st and ard protocol . This allowed the authors to examine all children identified through the vision-screening program . RESULTS Six-hundred eighty children were screened during the 1993 to 1994 school year . Eleven percent ( 76 ) failed the vision screening and were examined , 68 of whom failed the ophthalmic examination . The estimated prevalence of visual morbidity was as follows : amblyopia , 3.9 % ; strabismus , 3.1 % , and refractive errors , 8.2 % . CONCLUSION Amblyopia , strasbismus , and refractive errors were found in relatively high frequencies for this population sample of inner city children . These findings underscore the necessity of comprehensive vision-screening programs that integrate follow-up care . Children with limited access to specialized eye care must be provided with a mechanism for obtaining these services BACKGROUND New , small-target ( < 1 degree ) r and om dot stereogram ( STRDS ) and binocular suppression ( STBS ) tests appropriate for preschool vision screening were developed to correct the shortcomings of previous such tests , particularly missed cases of anisometropic amblyopia such as found with some RDS-based testing . METHODS In Experiment 1 , the tests were administered to 14 patients with current or a recent history of moderate ( < or = 20/60 ) anisometropic amblyopia , or with accommodative esotropia or monofixation syndrome . All subjects had good binocularity ( < or = 100 " contour stereoacuity ) . In Experiment 2 , the new tests were administered in a screening setting to a group of 112 three- to five-year-olds to determine testability . Visual acuity , cover testing , and photoscreening were administered as control measures . RESULTS In Experiment 1 , eleven of the 14 patients failed both tests . Two anisometropic amblyopes passing one or both tests had an acuity < or = 20/30 in the worse eye and < or = 25 " stereoacuity . Three anisometropic amblyopia patients failing the STRDS passed another RDS test with similar disparity but a larger target size , confirming a report34 that anisometropic amblyopes may pass RDS testing with parafoveal stereopsis despite the presence of central suppression . The STRDS and STBS tests indicated 80 % and 96 % specificity , respectively , with the original method ologies ; STRDS specificity increased to 95 % with retesting with a different methodology . Administration time was 30 sec to 60 sec per test . CONCLUSION Small-target RDS or suppression testing may be more effective for strabismus and amblyopia screening of preschoolers than previous RDS test formats Purpose The purpose of this study was to determine whether experience improves detection of small eye movements similar to those seen in the cover test during ideal conditions . Methods Three groups of examiners with varying amounts of experience in eye movement detection tasks were studied . Eight examiners were 1st-year optometry students , six were 4th-year optometry students , and six were practicing optometrists . To determine thresholds for eye movement detection , examiners indicated the horizontal direction in which the eyes of one of the experimenters moved . The direction and extent of each eye movement was r and omly selected . The extent of the eye movement was one of eight logarithmic steps from a maximum that was determined through an initial session where the approximate sensitivity of the examiners was found ( generally ± 1.75 prism diopters ) . Results Detection thresholds were determined by fitting the data with a cumulative Gaussian function . The mean horizontal eye movement eye movement necessary to obtain 99 % correct judgments was 2.65 prism diopters for the 1st-year students , 2.47 prism diopters for the 4th-year students , and 2.40 prism diopters for the practicing optometrists . Conclusions The results indicate that during ideal conditions , little or no training is required for efficient detection of small eye movements In this investigation , carried out under a Youth Health Care postgraduate course in Nijmegen , the stereopsis of a school population of 730 children , aged 4 - 18 years , was recorded and clinical ly evaluated . Stereopsis was measured using the TNO test , a r and om-dot stereo test especially design ed for the early detection of amblyopia . The main aims of this study were to establish the validity of the TNO test as a screening test for amblyopia , obtain information about the variability and age dependence of stereopsis , and to evaluate the efficacy of amblyopia prevention . The most important findings can be summarized as follows : 1 . All amblyopes are detected by the TNO test 's recommended referral criterion of 240 sec arc ( binocular threshold parallax in sec arc ) . 2 . The red-green anaglyphs used in the test do not pose problems for individuals with a colour vision deficiency . 3 . The ability to discriminate depth improves by a factor of two over the age interval 4 - 12 years . 4 . A stereoacuity of < or = 120 sec arc is a good predictor of normal or correctable normal vision , and may therefore help in evaluating the often incomplete results of eye tests of young children . 5 . Where there is an increased perinatal risk , there is a greater chance of disturbed binocular vision . 6 . It is estimated that 75 % of amblyopes remain amblyopic , possibly because of delayed detection ; 60 % of the amblyopes in the population examined were not identified before the age of 5 years In a short paper such as this , it would be a mistake to attempt a comprehensive review of our knowledge of the occurrence of strabismus and those characteristics of population s which may lead to variations in its incidence . To do so would subject us all to mental dyspepsia from a surfeit of information which none of us would have time to consider critically . Instead , I propose to take certain aspects of the epidemiology of strabismus , and to illustrate these by some observations made in Cardiff , with occasional data from other sources . The sort of questions we can hope to answer by epidemiological studies are those concerned with the prevalence of squint : How common is it ? Does the prevalence vary from one community to another , and if so , can we identify any characteristics of these communities which may explain the difference ? How do new cases arise , and at what ages ? The first of these questions can be answered reasonably accurately , but the others present difficulties . The common snag in population research is that a study of previously published work reveals that sampling methods and criteria used in definition are either not stated or differ so much from one another that it would be most unwise to draw any conclusions from comparisons of prevalence . As a result , it becomes necessary to use mainly internal comparisons , and in particular the techniques of comparing a group of strabismic patients with a group of non-strabismic patients drawn at r and om from the original population , and examined by the same techniques . A number of the comparisons I shall present comes into this category In 2003 the American Association for Pediatric Ophthalmology and Strabismus Vision Screening Committee proposed criteria for automated preschool vision screening . Recent literature from epidemiologic and natural history studies , r and omized controlled trials of amblyopia treatment , and field studies of screening technologies have been review ed for the purpose of updating these criteria . The prevalence of amblyopia risk factors ( ARF ) is greater than previously suspected ; many young children with low-magnitude ARFs do not develop amblyopia , and those who do often respond to spectacles alone . High-magnitude ARFs increase the likelihood of amblyopia . Although depth increases with age , amblyopia remains treatable until 60 months , with decline in treatment effectiveness after age 5 . US Preventive Services Task Force Preventative Services Task Force guidelines allow photoscreening for children older than 36 months of age . Some technologies directly detect amblyopia rather than ARFs . Age-based criteria for ARF detection using photoscreening is prudent : referral criteria for such instruments should produce high specificity for ARF detection in young children and high sensitivity to detect amblyopia in older children . Refractive screening for ARFs for children aged 12 - 30 months should detect astigmatism > 2.0 D , hyperopia > 4.5 D , and anisometropia > 2.5 D ; for children aged 31 - 48 months , astigmatism > 2.0 D , hyperopia > 4.0 D , and anisometropia > 2.0 D. For children > 49 months of age original criteria should be used : astigmatism > 1.5 D , anisometropia>1.5 D , and hyperopia > 3.5 D. Visually significant media opacities and manifest ( not intermittent ) strabismus should be detected at all ages . Instruments that detect amblyopia should report results using amblyopia presence as the gold st and ard . These new American Association for Pediatric Ophthalmology and Strabismus Vision Screening Committee guidelines will improve reporting of results and comparison of technologies BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects OBJECTIVES . This pilot study was design ed to assess the ability of a photoscreening camera to detect amblyogenic factors such as high refractive error , anisometropia , media opacities and strabismus in children , compared to the st and ard vision screening techniques employed by the local state public health screening personnel . METHODS . Public health personnel in Illinois used the Eyecor prototype to the current commercially available MTI PS-100 photoscreening camera ( manufactured by Medical Technology Inc. ) to screen 127 non-dilated subjects , ages 7 months to 20 years ( mean age , 6 years ) , for amblyogenic factors . All participants were concurrently subjected to the " st and ard " vision screening employed routinely by state public health personnel . The study participants included a group of normal inner-city children and one group of special-needs children . The normal children came from both a public school and a private school . The special-needs children included a group of children from a state-run school for the deaf and hard-of-hearing and a separate group of children attending a multi-disciplinary Easter Seals clinic . RESULTS . In the population of normal children , the mean sensitivity and specificity for the observers using the Eyecor Camera system was 81 % and 83 % with a mean positive predictive value of 83 % , and a mean negative predictive value of 55 % . St and ard vision screening techniques employed by public health service certified vision screeners had a sensitivity of 88 % , a specificity of 91 % , a positive predictive value of 67 % and a negative predictive value of 97 % in the same subjects . In the population of special-needs children with hearing impairment and developmental delay , the mean sensitivity and specificity for the observers using the Eyecor Camera system was 74 % and 82 % with a mean positive predictive value of 69 % and a mean negative predictive value of 85 % . St and ard vision screening techniques employed by public health service certified vision screeners had a sensitivity of 100 % , a specificity of 55 % , a positive predictive value of 62 % and a negative predictive value of 100 % in the same subjects . ( See Table 1 ) CONCLUSIONS . This study shows that the Eyecor Photoscreening Camera is useful in screening normal children for amblyogenic factors . Photoscreening was at least as effective as st and ard screening method ologies performed by certified vision screeners as required by state public health policy . In addition , photoscreening is particularly useful in testing those children " unscreenable " by conventional vision screening procedures PURPOSE To investigate the cost-effectiveness of a novel home-based screening system for amblyopia and amblyogenic risk factors . DESIGN Evaluation of diagnostic test or technology . PARTICIPANTS Two thous and four hundred forty-two preschoolers 3 to 6 years of age from 10 kindergartens r and omly selected from Guangzhou participated in the study in 2009 . METHODS Preschoolers were assessed for amblyopia and amblyogenic risk factors by their parents using the home-based screening system and were re-evaluated by professionals who conducted a comprehensive eye examination . MAIN OUTCOME MEASURES Sensitivity , specificity , positive predictive value , negative predictive value , and the cost-benefit of the home-based screening system were calculated by comparing the results from the home-assessed model and those from the professional evaluation . RESULTS Three thous and three hundred children were invited to participate in the study , and 2308 ( 1216 boys and 1092 girls ) completed all of the procedures . Twenty-four amblyopes were found by professional examinations . Fifteen of these amblyopes had not been diagnosed previously , and 12 of them were detected by the home- assessment model . The sensitivity , specificity , positive predictive value , and negative predictive value were 80.0 % , 94.1 % , 8.2 % , and 99.9 % , respectively . Professional examinations cost an average of US $ 1131.00 per case of amblyopia detected , whereas the cost was only US $ 266.00 per case for the home-based method . For amblyogenic factors , 50 , 87 , and 96 children were classified into grade I , II , or III according to the professional examinations . The corresponding numbers in the home-based system were 23 , 29 , and 15 , respectively . Accordingly , the true positive rates were 46.0 % , 33.3 % , and 15.6 % for each grade . CONCLUSIONS The home-based amblyopia screening system was found to be a simple , effective , and cost-beneficial method for amblyopia screening and amblyogenic risk factors . The approach offers a practical option for developing areas with large population s. FINANCIAL DISCLOSURE(S ) The author(s ) have no proprietary or commercial interest in any material s discussed in this article Stereoacuity was investigated in 3- to 5-year-old children and in adults by using four commercially available stereotests ( the Frisby , R and ot circles , R and om-Dot E ( RDE ) , and TNO tests ) and by using an experimental stereotest . Comparative re analysis was also made of data obtained from other studies of the RDE and Titmus circles tests . Stereoacuity norms are proposed for 3- to 5-year-old children for each of the commercially available tests . Factors influencing stereoacuity threshold differences among the different tests are discussed . The results on all tests are consistent with the hypothesis that binocular visual development is incomplete at 5 years of age BACKGROUND New photoscreening models promise to detect amblyopia risk factors early in hopes of reducing permanent pediatric monocular and binocular vision impairment . The 3 commercially available interpreted photoscreeners had not yet been compared . METHODS This is a prospect i ve , observational screening study following AAPOS guidelines on pediatric patients with and without developmental delays . 270 patients in a pediatric eye practice aged 4.7 + /- 4 years with 7 % special needs . From December 2011 through March 2012 , the Plusoptix , the iScreen , and the Pediavision SPOT were applied before confirmatory exam in a clinical pediatric eye practice . RESULTS The inconclusive rate ranged from 1 - 4 % ( iScreen ) to 12 % ( Plusoptix ) . Sensitivity ranged from 72 % ( iScreen ) to 84 % ( Plusoptix ) and specificity ranged from 68 % ( SPOT ) to 94 % ( Plusoptix ) . The iScreen can provide results in 99 % of high risk patients . CONCLUSIONS In this cohort with high pre-screening prevalence , the 2011 photoscreeners had favorable validation that is expected to improve with further clinical study . Pediatricians have practical technology with a recognized procedure code to assist in amblyopia reduction Objective . The purpose was to determine whether preschool children aged 3 years 0 months through 3 years 6 months could be tested with the R and om Dot E , Stereo Smile , and R and ot Preschool stereoacuity tests , which are r and om dot stereotests marketed for use with preschoolers . Methods . A total of 118 children from five Vision In Preschoolers Study Clinical Centers participated . Strabismic children , as determined by the cover test at distance and near , were excluded from this study . Stereopsis was tested on each child using each of the three tests in a variable , balanced order . A child ’s testability for each test was determined by the ability to complete the nonstereo task ( pretest ) and the gross stereo task for each stereotest . Proportions of children able to perform each test were compared using statistical methods accommodating multiple measurements per child . Results . Testability of children on the pretest was greater for the Stereo Smile test ( 91 % ) than for the R and om Dot E test ( 81 % ; p = 0.007 ) or the R and ot Preschool test ( 71 % ; p < 0.0001 ) and greater for the R and om Dot E test than for the R and ot Preschool test ( p = 0.02 ) . For all children , testability on the gross stereo task was greater for the Stereo Smile ( 77 % ; p < 0.0001 ) and R and om Dot E ( 74 % ; p = 0.005 ) tests than for the R and ot Preschool test ( 56 % ) but did not differ significantly between the Stereo Smile and R and om Dot E tests ( p = 0.19 ) . There were no significant differences among the proportion of children able to complete the gross stereo task among those who were testable on the pretest ( p > 0.12 , all comparisons ) . Conclusions . Among preschoolers aged 3 years 0 months through 3 years 6 months , testability differs significantly across the three commercially available r and om dot stereotests evaluated . The results suggest that two-choice procedures increase testability of young preschoolers Three r and om-dot stereogram ( RDS ) tests , the Frisby , R and om-Dot E ( RDE ) , and TNO tests , and a stereotest with monocularly visible contours , the R and ot circles test , were administered to two population s of 3- to 5-year-old children in vision screening setting s and to a sample of patients with strabismus and amblyopia . The Frisby test missed ( underreferred ) cases of binocular dysfunction detected by the RDE and TNO tests , using a 250 seconds of arc ( 250 " ) ( Frisby and RDE ) or 240 " ( TNO ) thresholds as the pass-fail breakpoint . The TNO underreferred cases at 240 " relative to the RDE , but underreferred none if the TNO 's breakpoint was lowered to 120 " . The R and ot circles test produced better-indicated stereoacuities than the RDS tests and was found able to reliably grade stereoacuity in patients with stereopsis too poor to be grade d by RDS tests This paper reports the outcomes of a study that compared the performance of 20 binocular adults on the Frisby stereotest and the TNO . ( All subjects were prescreened with the R and om-dot E stereotest administered at 1.5 m. ) Significant intercorrelations were found ( Pearson r = .73 ; two-tailed p less than .001 ) , adding support to the clinical usefulness of the Frisby stereotest . Other characteristics of the two tests -- including communication requirements and administration time -- are compared Aims To evaluate the accuracy and applicability of Plusoptix photoscreener in screening pre-verbal children at risk of amblyopia . Methods In this cross-sectional population -based study 996 children aged 6–36 months were screened with the Plusoptix . The children underwent complete examinations that included a manual cycloplegic retinoscopy , slit lamp examination , cover test , the Hirschberg test and an assessment of fixation pattern . In addition , the prevalence of amblyogenic risk factors was estimated , the Plusopix measurements were compared with cycloplegic retinoscopy , and the referral criteria were modified to improve the accuracy of the device . Results Amblyogenic hyperopia > + 3.50 D , myopia > −3.00 D , astigmatism > 1.50 D in the orthogonal meridian or > 1.00 D in the oblique meridian , or anisometropia > 1.50 D was detected in 4.7 % , 0.0 % , 12.3 % and 0.5 % of the sample s , respectively . The average difference between retinoscopy and photorefraction for spherical equivalence was −0.16±1.0 D ( p<0.05 ) . Testability was 98.1 % for the Plusoptix . The Plusoptix vision screener referred 47.8 % of these children for sensitivity , specificity , positive predictive value and false-negative rates of 100 % , 38.7 % , 19 % and 100 % , respectively . These same measurements with the modified referral criteria ( hyperopia ≥2.00 D in children under 12 months and astigmatism ≥1.25 D ) were 93.6 % , 51.2 % , 21.7 % and 98.2 % . Conclusion The Plusoptix is a useful objective screening instrument , but still has low specificity for detecting amblyopia risk factors in the paediatric population Though the Hirschberg test has been used for over a 100 years , several different formulas are still being recommended and used clinical ly to determine the amount of a given ocular deviation . The purpose of this study was to obtain a double-masked clinical evaluation of the Hirschberg test . Several strabismic patients were evaluated by one investigator using the alternate cover test and by another investigator using a photographic Hirschberg procedure in a double-masked procedure . It was determined that the Hirschberg test can be used for strabismic patients of all ages and that the most appropriate formula to use is 1 mm = 22 delta Abstract INTRODUCTION The rationale for preschool vision screening programmes has recently been question ed . Evidence about the effects of early treatment is needed , but it is not known how early the target conditions can reliably be detected . In this study , an intensive programme comprising several different screening methods , used at different ages up to 37 months , was compared with the usual practice of visual surveillance and ad hoc referrals . METHODS Two groups were r and omly selected from children in a population birth cohort study . The control group ( n = 1461 ) received visual surveillance only . The intervention group ( n = 2029 ) was offered in addition a programme of regular visual assessment s by orthoptists testing visual acuity , ocular alignment , stereopsis and non-cycloplegic photorefraction . RESULTS The intervention group programme yielded more children with amblyopia ( 1.6 % vs. 0.5 % , p < 0.01 ) , and was more specific ( 95 % vs. 92 % , p < 0.01 ) , than the control programme . The individual components of the intervention programme were compared . The cover test and visual acuity tests were poorly sensitive until the children were 37 months , but were always > 99 % specific . Photorefraction was more sensitive than acuity testing at all ages below 37 months , with specificity > 95 % at 31 and 37 months . CONCLUSIONS Photorefraction would have detected more children less than 37 months of age with straight-eyed amblyopia than did visual acuity testing , but with more false positives . At 37 months , photore-fraction plus a cover test would have been comparable in effectiveness to visual acuity testing plus a cover test The potential impact of the surgical correction of strabismus on vision-related quality of life ( VRQOL ) and the symptoms of anxiety and depression in children with strabismus remain unclear . The present study included 60 children with strabismus : 30 with heterophoria and 30 with heterotropia . A healthy age- and gender-matched control group ( n = 60 ) was also recruited . The psychological instruments that were used were the short-form 25-item National Eye Institute Visual Functioning Question naire ( NEI-VFQ-25 ) and the Hospital Anxiety and Depression Scale ( HADS ) . The results demonstrated that eight of the 12 NEI-VFQ-25 subscales were significantly impaired in children with strabismus compared with matched controls . Compared with pre-operative values , significant improvements were noted after surgery in the NEI-VFQ-25 summary score , and the anxiety and depression scores . This study demonstrated that the NEI-VFQ-25 instrument can be used in strabismus children and that surgical interventions can improve VRQOL , anxiety and depression in strabismus patients BACKGROUND Systematic review s that " compare " the accuracy of 2 or more tests often include different sets of studies for each test . PURPOSE To investigate the availability of direct comparative studies of test accuracy and to assess whether summary estimates of accuracy differ between meta-analyses of noncomparative and comparative studies . DATA SOURCES Systematic review s in any language from the Data base of Abstract s of Review s of Effects and the Cochrane Data base of Systematic Review s from 1994 to October 2012 . STUDY SELECTION 1 of 2 assessors selected review s that evaluated at least 2 tests and identified meta-analyses that included both noncomparative studies and comparative studies . DATA EXTRACTION 1 of 3 assessors extracted data about review and study characteristics and test performance . DATA SYNTHESIS 248 review s compared test accuracy ; of the 6915 studies , 2113 ( 31 % ) were comparative . Thirty-six review s ( with 52 meta-analyses ) had adequate studies to compare results of noncomparative and comparative studies by using a hierarchical summary receiver-operating characteristic meta-regression model for each test comparison . In 10 meta-analyses , noncomparative studies ranked tests in the opposite order of comparative studies . A total of 25 meta-analyses showed more than a 2-fold discrepancy in the relative diagnostic odds ratio between noncomparative and comparative studies . Differences in accuracy estimates between noncomparative and comparative studies were greater than expected by chance ( P < 0.001 ) . LIMITATION A paucity of comparative studies limited exploration of direction in bias . CONCLUSION Evidence derived from noncomparative studies often differs from that derived from comparative studies . Robustly design ed studies in which all patients receive all tests or are r and omly assigned to receive one or other of the tests should be more routinely undertaken and are preferred for evidence to guide test selection . PRIMARY FUNDING SOURCE National Institute for Health Research ( United Kingdom ) |
12,453 | 27,820,409 | With this limited evidence , no single intervention has been identified that offers a dramatic effect in terms of treating pain in the hemiplegic shoulder .
There is potential for some benefits for the patient 's functional and comfort status , thereby improving their quality of life and maximising their social participation .
Preventive interventions demonstrated that a shoulder positioning policy had no statistically significant effect on pain .
Some studies did suggest evidence of improvement , albeit limited .
However , some of the exercise techniques aggravated shoulder pain .
Treatment interventions demonstrated that electromyogram biofeedback can not be evaluated as a st and -alone therapy as it is used in conjunction with relaxation therapy .
Intra-articular Triamcinolone Acetonide injections in a small RCT have not been proven to be beneficial , and are associated with a high incidence of side-effects .
Different exercise techniques may aggravate shoulder pain more than others ( e.g. Bobath technique compared to cryotherapy ) .
The systematic review on the effectiveness of functional electrical stimulation was used for prevention and treatment and concluded that there is currently no evidence for effect | OBJECTIVE The objective of this review was to summarise the best available research related to the prevention and management of shoulder pain in the hemiplegic patient . | Background and Purpose Hemiplegic shoulder pain is not uncommon after stroke . Its origin is still unknown , and although many different methods of treatment are applied , none have yet been proved to be effective . We sought to study the efficacy of 3 injections of intra-articular triamcinolone acetonide on pain and arm function in stroke patients with hemiplegic shoulder pain . Methods In a multicenter , r and omized , placebo-controlled clinical trial , patients with hemiplegic shoulder pain received either 3 intra-articular injections of 40 mg triamcinolone acetonide or 1 mL physiological saline solution ( placebo ) . Primary outcomes were pain measured according to 3 visual analogue scales ( score range , 0 to 10 ) , and arm function was measured by means of the Action Research Arm test and the Fugl-Meyer assessment scale ; secondary outcomes were passive external rotation of the shoulder and general functioning measured according to Barthel Index and the Rehabilitation Activities Profile . Results In the triamcinolone group ( n=18 ) , the median decrease in pain , 3 weeks after the last injection , was 2.3 ( interquartile range , 0.3 to 4.3 ) versus 0.2 ( interquartile range , −0.5 to 2.2 ) in the placebo group . This result was not statistically significant . The change in the other outcome measures did not differ significantly between the 2 treatment groups . Twenty-five patients reported side effects . Conclusions In the 37 participants included in this study , triamcinolone injections seemed to decrease hemiplegic shoulder pain and to accelerate recovery , but this effect was not statistically significant . Therefore , on the basis of the results of this study , these injections can not be recommended for the treatment of patients with hemiplegic shoulder pain BACKGROUND AND PURPOSE Subluxation is a significant problem in poststroke hemiplegia , result ing in pain and loss of function . Current treatments are not proved and not considered effective . It has been demonstrated that cyclical electrical stimulation of the shoulder muscles can reduce existing subluxation . The purpose of this study was to determine whether electrical stimulation could prevent subluxation in both the short and long terms . METHODS A prospect i ve , r and omized controlled study was used to determine the efficacy of electrical stimulation in preventing shoulder subluxation in patients after cerebrovascular accidents . Forty patients were selected and r and omly assigned to a control or treatment group . They had their first assessment within 48 hours of their stroke , and those in the treatment group were immediately put on a regimen of electrical stimulation for 4 weeks . All patients were assessed at 4 weeks after stroke and then again at 12 weeks after stroke . Assessment s were made of shoulder subluxation , pain , and motor control . RESULTS The treatment group had significantly less subluxation and pain after the treatment period , but at the end of the follow-up period there were no significant differences between the 2 groups . CONCLUSIONS Electrical stimulation can prevent shoulder subluxation , but this effect was not maintained after the withdrawal of treatment BACKGROUND AND PURPOSE Visual analogue scales ( VAS ) have been used for the subjective measurement of mood , pain , and health status after stroke . In this study we investigated how stroke-related impairments could alter the ability of subjects to answer accurately . METHODS Consent was obtained from 96 subjects with a clinical stroke ( mean age , 72.5 years ; 50 men ) and 48 control subjects without cerebrovascular disease ( mean age , 71.5 years ; 29 men ) . Patients with reduced conscious level or severe dysphasia were excluded . Subjects were asked to rate the tightness that they could feel on the ( unaffected ) upper arm after 3 low-pressure inflations with a st and ard sphygmomanometer cuff , which followed a predetermined sequence ( 20 mm Hg , 40 mm Hg , 0 mm Hg ) . Immediately after each change , they rated the perceived tightness on 5 scales presented in a r and om order : 4-point rating scale ( none , mild , moderate , severe ) , 0 to 10 numerical rating scale , mechanical VAS , horizontal VAS , and vertical VAS . St and ard tests recorded deficits in language , cognition , and visuospatial awareness . RESULTS Inability to complete scales with the correct pattern was associated with any stroke ( P<0.001 ) . There was a significant association between success using scales and milder clinical stroke subtype ( P<0.01 ) . Within the stroke group , logistic regression analysis identified significant associations ( P<0.05 ) between impairments ( cognitive and visuospatial ) and inability to complete individual scales correctly . CONCLUSIONS Many patients after a stroke are unable to successfully complete self-report measurement scales , including VAS The purpose of this study was to evaluate the effectiveness of a functional electrical stimulation ( FES ) treatment program design ed to prevent glenohumeral joint stretching and subsequent subluxation and shoulder pain in stroke patients . Twenty-six recent hemiplegic stroke patients with shoulder muscle flaccidity were r and omly assigned to either a control group ( n = 13 ; 5 female , and 8 male ) or experimental group ( n = 13 ; 6 female , and 7 male ) . Both groups received conventional physical therapy . The experimental group received additional FES therapy where two flaccid/paralyzed shoulder muscles ( supraspinatus and posterior deltoid ) were induced to contract repetitively up to 6 hours a day for 6 weeks . Duration of both the FES session and muscle contraction/relaxation ratio were progressively increased as performance improved . The experimental group showed significant improvements in arm function , electromyographic activity of the posterior deltoid , range of motion , and reduction in subluxation ( as indicated by x-ray ) compared with the control group . We concluded that the FES program was effective in reducing the severity of shoulder subluxation and pain , and possibly facilitating recovery of arm function Ninety seven patients with stroke who had participated in a r and omised trial of conventional physical therapy nu an enhanced therapy for arm function were followed up at one year . Despite the emphasis of the enhanced therapy approach on continued use of the arm in everyday life , the advantage seen for some patients with enhanced therapy at six months after stroke had diminished to a non-significant trend by one year . This was due to some late improvement in the conventional therapy group whereas the enhanced therapy group remained static or fell back slightly . It is recommended that trials should be conducted comparing very intensive therapy for the arm with controls without treatment . This would provide a model of the effects of therapy on intrinsic neural recovery that would be relevant to all areas of neurological rehabilitation Previous research on stroke rehabilitation has not established whether increase in physical therapy lead to better intrinsic recovery from hemiplegia . A detailed study was carried out of recovery of arm function after acute stroke , and compares orthodox physiotherapy with an enhanced therapy regime which increased the amount of treatment as well as using behavioural methods to encourage motor learning . In a single-blind r and omised trial , 132 consecutive stroke patients were assigned to orthodox or enhanced therapy groups . At six months after stroke the enhanced therapy group showed a small but statistically significant advantage in recovery of strength , range and speed of movement . This effect seemed concentrated amongst those who had a milder initial impairment . More work is needed to discover the reasons for this improved recovery , and whether further development of this therapeutic approach might offer clinical ly significant gains for some patients Effects of intra-articular triamcinolone acetonide on pain and passive range of motion ( ROM ) in the painful hemiplegic shoulder were studied . A Multiple baseline ( or AB ) design across seven subjects was used . The length of the baseline condition ( or A phase ) was either 2 or 3 wk , and r and omized across subjects . Subsequently , a treatment condition ( or B phase ) of 4 wk was applied during which three intra-articular injections of triamcinolone acetonide were administered at day 1 , 8 , and 22 . Pain and ROM were the primary outcome parameters and were measured three times each week by means of a visual analogue scale ( VAS ) and a fluid-filled goniometer , respectively . In addition , a number of secondary outcome parameters were assessed , i.e. , spastic muscle activity ( Ashworth scale ) , motor function ( Fugl-Meyer index ) , upper limb function ( action research arm test ) and signs and symptoms of a shoulder h and syndrome ( clinical scoring list ) . Statistical analysis of the combined time series showed significant effects on pain ( P = 0.025 ) . Analysis of the individual time series revealed that five out of seven patients had significant reduction of pain . ROM improved significantly in four out of seven patients . However , improvement of ROM did not reach significance at the group level ( P = 0.13 ) . None of the secondary parameters showed significant changes . The correlation coefficient between upper limb function ( ARA ) at intake and size of treatment effect approached a level of significance ( P = 0.09 ) . The results indicate that intra-articular triamcinolone may be of benefit in reducing hemiplegic shoulder pain Shoulder pain and stiffness is a serious problem in patients following stroke . The purpose of this study was to investigate the effect of a shoulder positioning protocol on shoulder joint pain and range in the affected upper limb . Twenty-eight subjects were r and omly assigned to the experimental or control groups and participated in a multidisciplinary rehabilitation program . In addition , the experimental group received prolonged positioning of the shoulder daily for six weeks . Resting pain , pain on dressing , pain-free active abduction and passive external rotation range were measured on entry to the study and after six weeks . Twenty-three subjects completed the study . The differences between the groups were not statistically significant ( p < 0.05 ) , however , because of low statistical power the results are inconclusive The aim of this paper is to evaluate the effectiveness of high-intensity versus low-intensity transcutaneous electrical nerve stimulation ( TENS ) and versus placebo for treatment of hemiplegic shoulder pain . Three groups of 20 patients each ( A , B , C ) were studied . In group A high-intensity TENS was delivered at 3 times the sensory threshold with frequency of 100 Hz ; in group B low-intensity TENS was delivered at the sensory threshold with frequency of 100 Hz . Group C received placebo stimulation . The treatment protocol consisted of 12 sessions ( 4 weeks ) . Before treatment , at the end of it and one month after , passive range of motion ( PROM ) for flexion , extension , abduction and external rotation were evaluated . Statistically significant improvements of PROMs were recorded for group A , but not for groups B or The object of this study is to determine if the functional motor capacity of the paretic extremity can be improved by stimulation with low intensity low frequency ( 1.7 Hz ) transcutaneous electric nerve stimulation ( Low-TENS ) , started 6 - 12 months after a stroke . Forty-four patients who had a paretic arm as a consequence of their first stroke were included and r and omly assigned to either a treatment group ( n = 26 ) or a control group ( n = 18 ) . Patients in both groups received physiotherapy at a day-care center , usually twice a week . The treatment group received , in addition , Low-TENS for 60 min , five days a week for three months . Results showed that motor function increased significantly in the treatment group , compared to controls . The Low-TENS did not decrease either pain or spasticity . It is concluded that stimulation by means of Low-TENS could be a valuable complement to the usual training of arm and h and function in the rehabilitation of stroke patients One of the causes for shoulder pain associated with hemiplegia is thought to be vigorous range of motion to the involved upper extremity . The objective of this study was to analyze the occurrence of pain in patients treated with one of the three exercise programs commonly used in the rehabilitation of hemiplegia : 1 ) range of motion by the therapist , 2 ) skate board and 3 ) overhead pulley . Of the 48 hemiplegic patients evaluated , 28 were assigned to one of the three exercise groups . Comparing the number of patients who developed pain in each group , there was a significant difference , with 8 % of the patients in the range of motion by the therapist group , 12 % of the patients in the skate board group and 62 % of the patients in the overhead pulley group developing pain ( x2=8.44 ) ( P=0.014 ) . The three groups did not differ in the side of involvement ( P=0.57 ) , extent of hemiplegia ( P=0.25 ) or presence of subluxation ( P=0.84 ) . Use of overhead pulley has the highest risk of developing shoulder pain and should be avoided during rehabilitation of stroke patients Objective : To determine whether strapping the shoulder in hemiplegic stroke patients : ( 1 ) prevents the development , or reduces the severity , of shoulder pain , ( 2 ) preserves range of movement in the shoulder , and ( 3 ) improves the functional outcomes for the arm and patient overall . Design : A prospect i ve , r and omized , single-blind controlled trial of shoulder strapping versus no strapping . Setting : Care of the elderly wards in a teaching hospital , Christchurch , New Zeal and . Subjects : All patients admitted with an acute hemiplegic stroke , who had persisting weakness of shoulder abduction . Intervention : The treatment group had their affected shoulder strapped for six weeks from r and omization in addition to st and ard physiotherapy . Main outcome measures : All subjects were assessed at entry ( week 0 ) , at end of the treatment phase ( week 6 ) and two months later ( week 14 ) . A visual analogue scale ( VAS ) was used to assess shoulder pain severity whereas shoulder range of movement to the point of pain ( SROMP ) assessed passive range of movement and pain . Functional Independence Measure ( FIM ) , Motor Assessment Scale ( MAS ) and Rankin Disability Index measured functional outcomes . Results : Ninety-eight subjects participated ( 49 strapped , 49 controls ) . Intention to treat analysis showed no significant difference in pain , range of movement or functional outcomes after the intervention phase or at the final assessment . However there were trends for less pain at six weeks ( VAS , p = 0.11 ) and better final upper limb function ( MAS , p = 0.16 ) in strapped patients . Skin reactions were uncommon ( 6.1 % ) . The presence of neglect or sensory loss , but not subluxation , at baseline was independently associated with poor outcome . Range of movement was lost early ( mean difference SROMP between hemiplegic and contralateral shoulders at baseline = 15.2 ° ( 95 % CI 10.9–19.5 ) ) and continued throughout the study . Shoulder strapping did not alter the rate at which range of movement was lost . Conclusions : No significant benefit with shoulder strapping was demonstrated and reasons for this are discussed . Range of movement in the hemiplegic shoulder is lost very early and any preventive treatments need to begin within the first 1–2 days after a stroke BACKGROUND AND PURPOSE Shoulder pain is known to retard rehabilitation after stroke . Its causes and prognosis are uncertain . This study describes the incidence of poststroke shoulder pain prospect ively , in an unselected stroke population in the first 6 months after stroke and identifies risk factors for developing pain . METHODS 297 patients with possible stroke were screened and stroke diagnosed in 205 cases . The 152 patients entered the study of which 123 patients were assessed up to 6 months . This cohort , with a mean age of 70.6 years , was examined at 2 weeks , 2 , 4 , and 6 months . A history of shoulder pain , Barthel score , anxiety and depression score were recorded . Full neurological and rheumatological examination was undertaken , using the contralateral side as a control . Pain outcome and stroke outcome was recorded at subsequent visits . RESULTS 52 ( 40 % ) patients developed shoulder pain on the same side of their stroke . There was a strong association between pain and abnormal shoulder joint examination , ipsilateral sensory abnormalities and arm weakness . Shoulder pain had resolved or improved at 6 months in 41 ( 80 % ) of the patients with st and ard current treatment . CONCLUSIONS Shoulder pain after stroke occurred in 40 % of 123 patients surviving , consenting and not too unwell to participate . This included 52 patients of an original cohort of 205 patients presenting with stroke . Eighty percent of patients made a good recovery with st and ard treatment Patients with sensory and or motor deficits represent at risk sub-groups |
12,454 | 12,804,442 | Subgroup analyses failed to identify a disproportionate benefit of treatment according to the allergen administered .
Increasing duration of treatment does not clearly increase efficacy .
REVIEW ER 'S CONCLUSIONS SLIT is a safe treatment which significantly reduces symptoms and medication requirements in allergic rhinitis . | BACKGROUND Allergic rhinitis is a common condition which , at its most severe , can significantly impair quality of life despite optimal treatment with antihistamines and topical nasal corticosteroids .
Allergen injection immunotherapy significantly reduces symptoms and medication requirements in allergic rhinitis but its use is limited by the possibility of severe systemic reactions .
There has therefore been considerable interest in alternative routes for delivery of allergen immunotherapy , particularly the sublingual route .
OBJECTIVES To evaluate the efficacy of sublingual immunotherapy ( SLIT ) , compared with placebo , for reductions in symptoms and medication requirements . | Background : Local application of allergen extracts in specific immunotherapy is accompanied by increased compliance and significantly reduced side effects . However , efficacy of local immunotherapy in children has yet not been sufficiently demonstrated . This study was performed to determine clinical efficacy of high dose sublingual swallow immunotherapy ( SLIT ) by a double‐blind placebo‐controlled study in children with grass pollen allergy using high dose allergen extracts UNLABELLED SAFETY and efficacy of sublingual ( sublingual-swallow ) immunotherapy ( IT ) with house dust mite extract were evaluated in 30 children ( 6 - 15 2/3 years of age ) over the first 12 months of an ongoing study . The cumulative dose was 570 micrograms Der p I ( five times that administered with subcutaneous therapy ) . SAFETY One patient on active treatment dropped out after 8 weeks because of a subjective feeling of severe weakness , question ably induced by the therapy . Five patients on active therapy and one patient on placebo reported minor local side effects . EFFICACY Pulmonary symptoms were reduced after 12 months in actively treated asthmatics , but this was not consistent with the lack of improvement in bronchial reactivity , skin sensitivity and specific IgG and IgG4 against D.pt . in this group . In patients with rhinitis nasal sensitivity was reduced in the placebo group without concomitant improvement in the nasal symptom score . Specific IgE ( D.pt . and D.f . ) increased significantly more in the active treatment group after 3 and 12 months . We conclude that sublingual IT over 12 months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated , but there was no consistent clinical or immunological benefit compared to placebo A double-blind , placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route . The patients were assessed before and after a 10-month period of treatment by clinical ( symptom-medication scores and specific nasal reactivity ) and immunological ( total IgE , specific IgE , IgG and IgG4 antibodies ) parameters . High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects . The actively treated patients had significantly lower medication scores than those on placebo ( p < 0.05 ) when the maximum pollen count was recorded , and at the end of the trial they showed a significant decrease in nasal reactivity ( p < 0.02 ) and a significant increase in serum specific IgG4 ( p = 0.02 ) . No differences were detected in any of these parameters in the placebo group . Possible explanations for the mechanisms of sublingual immunotherapy are proposed Thirty-four patients suffering from rhinoconjunctivitis with or without asthma due to grass pollen , were su bmi tted to sublingual immunotherapy according to a double blind placebo controlled experimental plan ; eighteen patients received the active therapy , sixteen the placebo . A rush preseasonal treatment schedule was followed in order to reach the maintenance dose in 15 days with two administrations per day ; the top dose reached was then administered three times a week until the end of the pollen season . The symptoms and drugs related to rhinoconjunctivitis and asthma were recorded by means of diary cards and grass pollen counts were performed during the season . The actively treated group showed a reduction of symptoms of rhinoconjunctivitis and asthma and a lower intake of drugs for the same symptoms ; all these differences result ed to be statistically significant . No patient showed local or systemic side effects of any relevance . According to these results of our study , sublingual rush immunotherapy is clinical ly effective and because of the ease of h and ling , the shortness of the treatment , the absence of relevant side effects and the high compliance of the patient can be considered as an alternative to classic injective immunotherapy in grass pollen allergic patients 58 patients under 12 years of age , positive to mites ( Dermatophagoides pteronyssinus and D. farinae ) according to prick , in vitro specific IgE and challenge tests , suffering from asthma and rhinitis , have been r and omly assigned on a double blind basis to receive per os either a biologically st and ardized extract of mites ( active therapy TA = 30 patients ) or a saline buffered solution ( placebo TP = 28 patients ) . The serologic results are interesting . The specific IgE level differences of significance are , in comparison with the placebo group . In particular , we did observe the increase of the specific IgE level in the placebo group during the autumn , whereas after 12 months and after 24 months of active treatment there was a clear ( p < 0.01 ) decline in serum specific IgE antibody . In the active group , there was a significant increase in IgG antibodies level after 12 and 24 months and a significant increase in IgG4 level after 24 months . In the placebo group , the level of IgG antibodies was unchanged . In the actively treated patients , a significant increase of CD8 + values and a significant reduction of the ratio CD4+/CD8 + was observed BACKGROUND Sublingual swallow immunotherapy has been increasingly recognized as a safe and efficacious alternative to parenteral specific immunotherapy . OBJECTIVE To determine the safety and efficacy of sublingual swallow immunotherapy ragweed allergen extract for rhinoconjunctivitis treatment starting just before and continuing through the ragweed pollen season . METHODS This r and omized , double-blind , placebo-controlled study was performed in children and adults with a documented history of allergic rhinoconjunctivitis during ragweed season at 9 Canadian allergy centers . Active treatment was st and ardized extract of ragweed allergen administered as sublingual swallow drops at increasing doses starting shortly before the pollen season and maintenance doses continued daily during the season . Primary efficacy variables were symptom and medication scores , and secondary variables included global evaluation of efficacy and immunologic measurements . RESULTS Eighty-three patients were included in the safety analysis ; 76 patients were included in the intent-to-treat analysis . Nine placebo recipients and 1 treatment recipient withdrew for lack of efficacy ( P = .004 ) . Nine patients in the treatment group withdrew because of adverse events , none serious ( P = .003 ) . Investigator evaluation of efficacy showed that significantly more patients improved and fewer deteriorated in the treatment group vs the placebo group ( P = .047 ) . Ragweed IgE and IgG4 levels increased significantly in treatment recipients vs placebo users ( P < .001 ) . Sneezing and nasal pruritus approached significant improvement in the treatment group vs the placebo group ( P = .09 and .06 , respectively ) . Quebec City experienced low pollen counts . Excluding Quebec City , significant improvement was seen for these 2 symptoms ( P = .04 ) . CONCLUSION Sublingual swallow immunotherapy seems to be safe and efficacious for ragweed rhinoconjunctivitis even when started immediately before the ragweed pollen season Background : Especially in childhood , sublingual immunotherapy ( SLIT ) could offer advantages over subcutaneous therapy . However , limited data on its efficacy is available Sublingual immunotherapy has been suggested for the treatment of respiratory allergies . Many controversial studies have been reported on the efficacy of sublingual immunotherapy . The aim of this prospect i ve study was to evaluate whether sublingual immunotherapy was effective according to clinical and laboratory results in pediatric allergies . Thirty-nine allergic , grass pollen sensitive children were admitted into the study . Sublingual immunotherapy was given over a 12-month period to 21 children ( mean age 10.5 + /- 3.3 years ) , 10 of whom had seasonal allergic rhinitis and 11 seasonal allergic asthma . During the same period , 18 children ( mean age 11.1 + /- 2.5 years ) , 10 with seasonal allergic rhinitis and eight with seasonal allergic asthma , received placebo . Symptom scores and drug requirements were recorded and urine sample s were collected to detect urinary levels of leukotrienes ( Uc-LTB4 and Uc-LTE4 ) . In patients who received sublingual immunotherapy , the symptom scores of seasonal allergic rhinitis significantly decreased , but no statistically significant changes were observed in terms of symptoms of seasonal allergic asthma . Uc-LTE4 and Uc-LTB4 levels of seasonal allergic rhinitis , with a geometric mean and 95 % confidence interval ( CI ) , were significantly decreased from 216 ( 103 - 464 ) and 61 ( 22 - 198 ) pmol/mmol creatinine to 78 ( 29 - 159 ) and 35 ( 12 - 118 ) pmol/mmol creatinine , respectively ( p < 0.05 and p < 0.05 ) . On the other h and , Uc-LTE4 and Uc-LTB4 levels for seasonal allergic asthma were 180 ( 92 - 355 ) and 78 ( 44 - 258 ) pmol/mmol creatinine and decreased to 156 ( 72 - 402 ) and 69 ( 32 - 254 ) pmol/mmol creatinine , respectively . These changes were not statistically significant ( p > 0.05 ) . According to our clinical results and urinary levels of leukotrienes , which are mediators showing the severity of allergic inflammation , it can be suggested that sublingual immunotherapy may be useful in the treatment of seasonal allergic rhinitis but not of seasonal allergic asthma BACKGROUND sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy . Allergy to alder , birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe . METHODS thirty patients , selected and observed for one pollen season , were r and omised to receive placebo ( 15 patients ) or active treatment ( 15 patients ) . Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs . Symptom and drug scores during each pollen season , birch-specific IgE , changes in skin test reactivity , changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment . RESULTS both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year , under a lower allergenic pressure . The improvement was higher in the active group ( 76.04 % reduction of drugs ) but not significantly different from that registered in the placebo group ( 37.05 % reduction ) . In the open phase of the study , treated patients showed significantly better scores in comparison to the control group . No significant changes in skin reactivity , specific IgE and Nasal Provocation Test were registered . SLIT tolerance was very good . CONCLUSIONS our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT , but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy Sublingual‐swallow immunotherapy ( SLIT ) using high doses of st and ardized allergen extracts has been found to be effective in reducing allergic symptoms and medication needs . A double‐blind , placebo‐controlled study was carried out in a large number of patients to determine whether medication needs can be reduced by SLIT . Some 136 patients with grass‐pollen rhinitis with or without mild asthma were studied . Patients received either placebo or SLIT with a st and ardized grass‐pollen extract administered daily with increasing doses up to 300 IR ( index of reactivity ) from January to the end of July 1994 . During the grass‐pollen season , patients were instructed to use medications as required and to visit their doctors in case of asthma . Symptom‐medications scores were assessed during the pollen season , and serum‐specific IgG4 was measured before and at the end of SLIT . In the SLIT group , drug consumption dropped significantly throughout the pollen season ( P<0.02 ) . Moreover , at the peak of the pollen season , betamethasone consumption was significantly reduced in the SLIT group ( P<0.02 ) . Only one patient in the SLIT group had an asthma attack compared to eight patients in the placebo group ( P<0.02 ) . IgG4 levels increased significantly in the SLIT group ( P<0.001 ) but without correlation with symptoms . Side‐effects were comparable in both groups . This study indicates that SLIT in grass‐pollen rhinitis is well tolerated , improves overall clinical symptoms , and reduces drug consumption and the need for oral corticosteroids In a double-blind , placebo-controlled , pilot clinical trial we evaluated the clinical efficacy and safety of immunotherapy ( IT ) with an extract of the pollen of the tree Olea europaea administered sublingually . The parameters tested were symptom score , dose-response bioassay of skin prick test and specific IgE and IgG , and the absolute value at a single serum dilution of each IgG subclass . Fifteen patients allergic to this pollen with symptomatology of rhinitis and /or rhinoconjunctivitis were r and omly allocated to the placebo group ( 6 patients ) or to the extract group ( 9 patients ) . Immunotherapy was administered in a short preseasonal period of time , practically no side effects being recorded . The group of patients treated with extract presented a slightly lower incidence ( 0.05 < p < 0.1 ) of nasal symptoms of sneezing and obstruction , and , more importantly , developed less dyspnea ( p < 0.05 ) than the group treated with placebo , suggesting that IT can act as prophylaxis for the development of bronchial symptoms . No differences were observed in the immunological determinations . Differences in skin tests between the two groups displayed a slight significance ( 0.05 < p < 0.1 ) at the end of the trial ; hence , a higher concentration of the allergen was needed in the group treated with extract to induce the same wheal as in the placebo group . In both groups the size of the wheal showed a time-dependent variation , which was dependent on the time of the year and independent of the type of treatment received , indicating a significant modification in the in vivo skin response to allergen challenge , demonstrated by a shift in the kinetics of allergen-lig and binding ( slope ) and in the magnitude of the measured response ( intercept ) Little knowledge is available on molds either from the environmental or clinical points of view . The latter is mainly due to the lack , until recent times , of purified and st and ardized extracts . Injective immunotherapy , largely used for patients allergic to mites and pollens , is regarded with some concern for molds . On the other h and , mold-related allergic symptoms ( i.e.,from Alternaria tenuis ) have in Italy an incidence of about 5 percent , mainly in young patients . We have therefore run a pilot study comparing the efficacy and safety of injective ( SIT ) and sublingual ( SLIT ) immunotherapy by administering the same purified and st and ardized extract of Alternaria tenuis to a total of 23 patients for two years , according to an open experimental plan . Excellent tolerance was shown to SLIT while four ( two medium- grade ) side effects appeared with SIT . Clinical improvement , subjectively stated comparing symptoms ( mainly rhinitis ) and drug consumption before and after the therapy , confirmed by an increase in the Specific Nasal Provocation threshold , was obtained with both therapies , but with a statistically significant difference in favour of SLIT . Skin reactivity and blood Alternaria tenuis specific IgE , total IgG and IgG changed in the SIT-treated group , while no statistically significant change was shown in the SLIT-treated group . These results are in good agreement with previous reports on SIT and SLIT with other inhalant allergens ( mites , grasses ) , and suggest the potential use of SLIT for Alternaria allergy , mainly in young patients , when there are concerns about the safety of and compliance with the traditional injective therapy BACKGROUND Immunotherapy involves the modulation of allergen-specific T-cell responses , either T(H)2-to-T(H)1 immune deviation or , in bee venom-treated patients , induction of IL-10 production by CD4+CD25 + T cells . IL-10-producing CD4+CD25 + regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology . OBJECTIVE The aim of this study was to evaluate the role of IL-10 production and CD4+CD25 + T cells in the response to grass pollen immunotherapy . METHODS P BMC s were isolated from patients after 1 year of grass pollen immunotherapy and from matched untreated atopic and healthy control subjects . After 6 days of in vitro stimulation with Phleum pratense , production of IL-10 , IL-5 , IL-4 , and IFN-gamma and proliferation and numbers of CD4+CD25 + T cells were measured . T cells were then stimulated for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed for intracellular IL-10 by means of flow cytometry . RESULTS Patients undergoing immunotherapy produced significantly more IL-10 than atopic control subjects ( patients undergoing immunotherapy , 116 + /- 21 pg/mL [ n = 11 ] ; atopic patients , 30 + /- 5 pg/mL [ n = 11 ] ; P < .001 ) , and the number of CD4+CD25 + cells identified after allergen stimulation was also greater in the immunotherapy group . The numbers of CD4+CD25 + T cells correlated positively with activation as measured by proliferation in both of the control groups but not in the immunotherapy group . Moreover , only T cells from patients undergoing immunotherapy were positive for intracellular IL-10 , and these were almost exclusively CD4+CD25 + cells . CONCLUSION Grass pollen immunotherapy results in a population of circulating T cells that express the IL-10(+ ) CD4+CD25 + phenotype in response to allergen restimulation BACKGROUND Non-injective routes of immunotherapy are thought to be valuable therapeutic options for respiratory allergy . We investigated the clinical efficacy and the effects of sublingual/oral immunotherapy on conjunctival allergic inflammation in patients with mite-induced respiratory allergy . METHODS We used a double-blind placebo-controlled design . 20 patients with mite-induced rhinoconjunctivitis ( six of whom also had mild asthma ) were r and omly assigned sublingual/oral immunotherapy ( n=10 ) or placebo ( n=10 ) for 2 years . We assessed symptom score by diary cards and inflammatory-cell infiltrate , and expression of intercellular adhesion molecule 1 ( ICAM-1 ) in the conjunctiva after specific allergen challenge at enrollment and after 12 and 24 months of treatment . FINDINGS We found significantly lower symptom scores in the immunotherapy group than in the placebo group in most of the winter months ( p=0.05 ) . Compared with the placebo group , inflammatory-cell infiltration after conjunctival challenge , and ICAM-1 expression on conjunctival epithelium decreased significantly in the first year of treatment in the immunotherapy group ( p=0.04 and p=0.02 , respectively ) . These effects were also seen for the minimum persistent inflammation , in symptom-free patients exposed constantly to allergens ( p=0.02 ) . Serum concentrations of eosinophil cationic protein decreased significantly ( p=0.04 ) . Immunotherapy was well tolerated and compliance was good . INTERPRETATION Our results suggest that this immunotherapy is clinical ly effective in rhinoconjunctivitis and that it decreases the immune-mediated inflammatory responses to the allergen UNLABELLED Sublingual immunotherapy ( SLIT ) has been recognized as a viable alternative to subcutaneous immunotherapy for respiratory allergies both in adults and children , but clinical documentation about safety and efficacy in children is still poor . The purpose of this study was to assess the efficacy and tolerance of SLIT in children who are sensitized to grass pollen . METHODS Children with a clinical history of intermittent rhinoconjunctivitis , with or without mild asthma and positive skin prick tests to grass pollen , were selected to participate in a 2-year double-blind , placebo-controlled study with SLIT , using a grass extract ( ALK-Abellò ) . RESULTS 22 children were analyzed at the end of the study . No relevant side effects occurred in the active group . A statistically significant difference ( p = 0.05 ; Mann-Whitney test ) in favor of the active group ( n = 10 ) could be shown for drug consumption during the second year , as well as a significant improvement as compared to the first year of SLIT ( p = 0.05 ; Wilcoxon test ) . CONCLUSIONS Despite the small number of patients , our data suggest that SLIT with a grass pollen extract is well tolerated in children and is able to significantly reduce drug consumption during the second year of treatment . Studies in larger groups of children sensitized to both grass and tree pollens are needed to definitively assess the role of SLIT in intermittent , seasonal rhinitis and pollen asthma Background Immunotherapy is a recognized treatment for allergic respiratory diseases Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy ( SLIT ) is highly beneficial . Twenty-four children ( age 4 - 16 ) monosensitized to house dust mite were r and omized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design ( Marcucci et al. , Allergy 2003 : 58 : 657 - 62 ) . Thereafter , for 2 yr they all received active treatment . Symptom scores for rhinitis , asthma , and drug usage were daily recorded . Eosinophil cationic protein ( ECP ) and tryptase in sputum and nasal secretions , serum and nasal mite-specific immunoglobulin E ( IgE ) were recorded before treatment and at 10 - 12 months intervals . Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values ( p = 0.0043 and 0.0195 , respectively ) in the third year of active treatment . None of the other inflammatory parameters was increased . In placebo treated patients all these parameters tended to decrease only after switching to active treatment . Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study . In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline . A significant difference was reached in patients treated for 2 yr for rhinitis and asthma ( p = 0.0009 and 0.0019 , respectively ) but not for drug usage and in patients treated for 3 yr for rhinitis , asthma , and drug usage ( p = 0.0105 , 0.0048 , and 0.02 , respectively ) . SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation . These outcomes were followed by a consoli date d clinical improvement in the second and third year of treatment Background Symptoms of allergic rhinitis are accompanied by infiltration of the nasal mucosa with inflammatory cells , predominantly eosinophils and metachromatic cells ( basophils and mast cells ) . Specific immunotherapy ( IT ) reduces mucosal eosinophilia and numbers of metachromatic cells in the epithelium . A specific marker distinguishing basophils from mast cells was recently developed Background Previous studies suggest that sublingual immunotherapy ( SLIT ) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed To evaluate the efficacy of specific sublingual immunotherapy ( SLIT ) , we enrolled 15 children with asthma and rhinitis ( 7 girls , 8 boys , mean + /- SD age of 11.7 + /- 3.3 ) allergic to house dust mite ( HDM ) into a double-blind , placebo-controlled study . After a run-in period , patients were r and omized to receive either placebo ( n = 7 ) or SLIT ( n = 8) with a st and ardized Dermatophagoides pteronyssinus ( D. pteronyssinus ) + Dermatophagoides farinea ( D. farinea ) 50/50 extract . They received increasing doses up to 100 index units of reactivity ( IR ) every day for 4 weeks , then 100 IR/day for another 4 weeks , followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months . Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores , serum total IgE levels , results of lung function tests , methacholine provocation tests , and skin prick tests . Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group ( P = 0.05 , P = 0.028 , respectively ) , whereas no such difference was observed in the placebo group . At the end of follow-up , mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group ( P = 0.04 ) . Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups , whereas end-point wheal diameter obtained with D. pteronyssinus extract was significantly less in the SLIT vs. the placebo group ( P = 0.026 ) . At the end of 6 months , peak expiratory flow ( PEF ) values in the placebo group was significantly lower than in the SLIT group ( P = 0.049 ) . Throughout the treatment period , the SLIT group was found to have less asthma exacerbations than the placebo group ( P = 0.007 ) . The provocation concentration causing a 20 % drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups . None of the patients reported local or systemic side effects from SLIT . Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM Conflicting results concerning the effect of specific pollen immunotherapy ( SIT ) on allergy to plant foods have been reported . The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple . Seventy-four birch pollen-allergic patients were included in a double-blind , double-dummy , and placebo-controlled comparison of sublingual-swallow ( SLIT ) and subcutaneous ( SCIT ) administration of a birch pollen extract . Sixty-nine percent of these patients reported allergy to apple . The clinical reactivity to apple was evaluated by open oral challenges with fresh apple and a question naire . The immunoglobulin E (IgE)-reactivity was assessed by skin prick test ( SPT ) , specific IgE , and leukocyte histamine release ( HR ) . Forty patients were included in the final evaluation of the effect of SIT . The challenges were positive in 9 ( SCIT ) , 6 ( SLIT ) , and 8 ( placebo ) patients after treatment compared to 10 , 4 , and 10 patients , respectively , before SIT . The symptom scores to apple during challenges decreased in all groups , but only significantly in the placebo group ( p = 0.03 ) . As evaluated by the question naire , the severity of food allergy in general did not change and there were no differences between the groups . In spite of a significant effect on seasonal hay fever symptoms and use of medication and decrease in IgE-reactivity , SIT was not accompanied by a significant decrease in the severity of allergy to apple compared to placebo . Therefore , oral allergy syndrome ( OAS ) to apple should not be considered as a main criterion for selecting patients for birch pollen immunotherapy at present A study of RUSH specific immunotherapy by sublingual route has been performed . Twenty patients have been studied suffering from rhinoconjunctivitis a/o allergic asthma to grass pollen , divided in two homogeneous groups . The first group was treated with immunotherapy , the other was used as a comparison in open . The level of specific IgG4 , specific IgE , drug consumption and the symptom score were monitored . The symptom and drug scores recorded by the patients during the pollen season were significantly reduced in the group undergoing sublingual allergen administration , thus proving the clinical efficacy of this treatment . There has not been , however , a significant reduction of specific IgE , nor a significant increase of specific IgG4 towards grasses , in the treated group , monitored before and at the end of the immunotherapy BACKGROUND Sublingual-swallow immunotherapy was recently recognized in the World Health Organization Position Paper ( Allergen immunotherapy : therapeutic vaccines for allergic diseases ) " as a viable alternative to parenteral injection therapy to treat allergic diseases " in adults . More controlled studies were required to assess the efficacy and safety of this treatment in children . OBJECTIVE This study was carried out to assess the clinical efficacy and safety profile of sublingual-swallow immunotherapy with high-dose allergen in children with allergies . METHODS We used a double-blind placebo-controlled design . Forty-one children with Parietaria -induced rhinoconjunctivitis were r and omized to receive sublingual st and ardized Parietaria judaica extract ( n = 20 ) or placebo ( n = 21 ) for 2 years . The cumulative dose of allergen was 375 times higher than that used in parenteral immunotherapy and the cumulative dose of Par j 1 major allergen was 52.5 mg over 2 years . The main efficacy assessment criteria were symptoms and rescue medication scores recorded on the patients ' diary cards . Secondary criteria were changes in skin and conjunctival specific reactivity as well as blood parameters , analyzed after 1 and 2 years of immunotherapy . The safety of the treatment was assessed by evaluating the frequency and severity of adverse effects . RESULTS A significant reduction in rhinitis symptoms was observed in the active treatment group during the second season ( P = .02 ) , with no difference in medication scores . A significant decrease in skin reactivity ( P = .002 after 2 years of treatment ) and an increase in the threshold dose for conjunctival allergen provocation test ( P = .02 ) were observed in the active treatment group compared with the group receiving placebo . A significant increase in specific IgG(4 ) levels ( P = .02 ) was also observed in the active group . Immunotherapy was well tolerated . CONCLUSION Sublingual-swallow immunotherapy in Parietaria -allergic children provided a clinical benefit and a decreased specific reactivity to the allergen . The safety profile of this treatment , which constitutes an important issue , indicated good tolerance and compliance BACKGROUND In light of the controversial status of sublingual immunotherapy in patients with allergic rhinitis , we undertook a double-blind study of this form of treatment . METHODS Forty-one subjects with cat allergy presenting as rhinoconjunctivitis underwent 105 days of sublingual immunotherapy , with 20 subjects receiving a st and ardized cat extract ( total dose approximately 4,500,000 allergy units ) and 21 a matching placebo . Effectiveness of treatment was assessed by changes in symptoms and nasal-blockage index during 90 minutes of exposure in an apartment containing cat d and er , which was performed before and after the course of treatment . Changes in cat-specific IgG and IgE levels and skin-test reactions were also monitored . RESULTS Although there were fewer symptoms and less nasal obstruction on cat d and er exposure at the end of the study the changes were not significantly different in those receiving active or placebo treatment . Specific IgG and IgE levels and prick skin test results did not change significantly during the course of the study . CONCLUSIONS We conclude that sublingual immunotherapy with high-dose st and ardized cat extract was no more effective than placebo in reducing symptoms or affecting immunologic measures of cat sensitivity The aim of this double-blind placebo-controlled study was to evaluate the efficacy and tolerability of short-term birch pollen sublingual immunotherapy . Forty-one patients suffering from allergic rhinoconjunctivitis caused by Betula alba were included . Exclusion criteria were the following : undergoing immunotherapy within the last 2 years , contraindications to immunotherapy , pregnancy and nursing . The treatment schedule comprised a 28-day basic course , followed by a 3-month maintenance treatment . The evaluation of the parameters was performed before treatment and 4 months after the last maintenance dose . Skin prick test and conjunctival provocation test ( CPT ) in a dilution series were carried out to determine the threshold of the reaction . The objective parameters used were the diameter of the skin wheals and the lowest concentration , of the allergen extract to induce the symptoms of itching and reddening of the eyes . The allergic reaction in general was evaluated with the help of a 2-h birch pollen challenge in the Vienna Challenge Chamber ( VCC ) ; nasal flow and resistance was measured by rhinomanometry ; and nasal secretion was quantified by weighing used h and kerchiefs . Bronchial reactions were objectified by spirometry ; subjective symptoms of the eyes , the nose and the bronchial tract were documented by the patients via a visual analog scale . Birch pollen specific IgE and IgG were evaluated by monoclonal antibody enzyme immunoassay before ( T0 ) and after ( T1 ) treatment . For statistics p < 0.05 was applied . At T0 there was no decisive difference in the in vitro and in vivo results between the two groups . After the treatment period ( T1 ) , actively treated patients showed a significantly higher tolerance to the birch pollen CPT ( p < 0.01 ) . The skin reaction was significantly lower than in the placebo group . Furthermore , actively treated patients produced less than half of the nasal secretion of placebo-treated patients during the challenge session . The rhinomanometry analysis during the challenge showed significant differences for verum and placebo in favor of the actively treated patients ( p = 0.033 ) . There was no significant difference in the specific IgE and IgG concentrations . The side effects and compliance during the treatment were comparable in both groups . In conclusion , sublingual immunotherapy is a well tolerated and clinical ly effective method of treatment Fifty eight patients under 12 years of age , positive to mites ( Dermatophagoides pteronyssinus and D. farinae ) according to prick , " in vitro " specific IgE and challenge tests , suffering from asthma and rhinitis , were r and omly assigned on a double blind basis to receive per os either a biologically st and ardized extract of mites ( active therapy TA = 30 patients ) or a saline buffered solution ( placebo = 28 patients ) . Patients took sublingually increasing doses of the solution , followed by maintenance therapy consisting of 15 drops 3 times a week . The results of the trial were assessed after 12 an 18 months , according to the following parameters : symptom scores recorded in diary cards , total and specific IgE levels , total IgG level , IgG1 and IgG4 levels , lymphocytes under population s , nasal challenge test , side effects . During the first 18 months , the patients on active therapy had significantly lower scores ( p less than 0.001 ) and clear variations of rhinomanometric parameters ( p less than 0.01 ) ; IgG also significantly increased . After 12 months , bronchial specific and specific challenge tests showed significantly higher threshold values in comparison to initial values ( p less than 0.05 ) . No statistically significative variation was registered in the placebo group Background : Clinical documentation about effects on local markers of inflammation of sublingual immunotherapy ( SLIT ) in children is still poor Background Injective immunotherapy is a well‐known and recognized treatment for allergic diseases , but its safety has been question ed during recent years . Alternative administration routes have been proposed and there is a growing interest and experience in sublingual therapy . The safety of alternative routes is nonetheless a real advantage , so long as it is not counterbalanced by a loss of clinical benefit Background : New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy . We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica‐induced respiratory allergy For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose , 66 children with seasonal asthma , rhinitis , and conjunctivitis due to sensitization to olive pollen were enrolled in a double‐blind , r and omized , placebo‐controlled study between October 1994 and October 1996 in Greece . Thirty‐four patients were r and omly allocated to the active group , and 32 received placebo . Immunotherapy consisted of olive‐allergen extracts ( Stallergenes SA ) administered sublingually pre‐ and coseasonally from January to July for 2 consecutive years . Serial concentrations from 1 to 300 IR were used up to the maintenance dose of 20 drops of 300 IR daily . The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy , and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years . The patients were assessed by clinical parameters ( symptom and medication scores from patients ' daily diaries ) and immunologic measurements ( specific IgE. lgG4 . eosinophil cationic protein [ ECP ] ) were performed . The actively treated patients had a significantly lower score for dyspnea ( P<0.04 during the first season ; P<0.03 during the second season ) . At the poUinic peak during the second year , a lower score of conjunctivitis was recorded ( P<0.05 ) in the actively treated patients . The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo , whereas there was no symptomatic peak for the same period in the group under active treatment . However , the difference between the groups was not significant . The medication score did not differ significantly between the groups . Oral steroids were the only variables with a P value near the significance level ( P=0.06 ) in favor of the actively treated group . A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment . No significant variation in specific IgE and IgG4 was detected . A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season ( P=0.01 ) , but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings . Tolerance was excellent with only a few minor side‐effects reported . In conclusion , high‐dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive‐pollen sensitization BACKGROUND The immunologic response to allergen immunotherapy with 3 serial 5-fold doses of cat extract has been studied after approximately 5 weeks of immunotherapy . The highest dose containing 15 mug of Fel d 1 produced the most consistent and favorable response . It is unknown whether the comparative response on reaching a maintenance dose is maintained with long-term maintenance therapy . OBJECTIVE The purpose of this investigation was to evaluate the immunologic responses with these 3 serial doses of cat hair and d and er extract at baseline , after reaching the maintenance dose ( approximately 5 weeks ) , and after 1 year of maintenance immunotherapy . METHODS Twenty-eight patients with cat allergy r and omized in a double-blind study were assigned to one of 4 treatment groups : placebo or cat hair and d and er extract containing 0.6 mug of Fel d 1 , 3 mug of Fel d 1 , and 15 mug of Fel d 1 at maintenance . Studies included skin prick tests and late cutaneous reactions with cat hair and d and er extract , titrated nasal challenges with the extract , serum cat allergen-specific IgG4 and IgE measurement , and flow cytometric and ELISA analysis of whole blood and intranasal cytokines ( TGF-beta , IL-10 , IFN-gamma , IL-4 , and IL-5 ) . RESULTS Twenty-six subjects completed the study . After both 5 weeks and 1 year , significant and dose-dependent differences were seen with total symptom scores on nasal challenge ( P < .0001 ) , with titrated skin prick testing with cat d and er extract at 5 weeks ( P = .014 ) and 1 year ( P < .0001 ) , and with cat-specific IgG4 measurement at 5 weeks ( P = .004 ) and 1 year ( P = .003 ) . At 1 year , neither flow cytometry of whole blood nor ELISA evaluation of nasal cytokines demonstrated any significant differences among the treatment groups . CONCLUSION The response to titrated nasal allergen challenge , titrated skin prick testing , and allergen-specific IgG4 measurement to cat immunotherapy at 5 weeks is predictive of the response at 1 year The clinical efficacy of sublingual immunotherapy ( SLIT ) has been demonstrated , but its mechanism of action is still controversial . The most recent experimental observations suggest that a critical role in the modulation of immune response is sustained by Th2 cytokines , such as interleukin-4 ( IL-4 ) , IL-5 and IL-13 , by co-stimulatory molecules , such as CD40 on B cells , and by hormones and neuropeptides . To better underst and whether SLIT affects immune responses we used a double-blind placebo-controlled design . Eighty-six children with mild asthma due to allergy to Dermatophagoides pteronyssinus ( 33 of whom also had rhinoconjunctivitis ) were r and omly assigned SLIT ( n = 47 ) or placebo ( n = 39 ) . We assessed symptom scores using diary cards of each patient and determined the expression of CD40 on B cells and the serum concentration of ECP , IL-13 , prolactin ( PRL ) and ACTH at enrolment and after 6 months of therapy . We observed a significant reduction in asthma and rhinitis scores in the immunotherapy group compared with the placebo group , no variation in CD40 and ACTH , but a significant decrease in ECP , IL-13 and PRL after 6 months of therapy ( p < 0.01 ) . Our results confirm the efficacy and safety of SLIT , and lead us to believe that it could modulate the synthesis of Th2 cytokines , as revealed from the decrease of IL-13 . In addition , the reduction of PRL might be a signal of reduced activation of T lymphocytes Background : The efficacy and safety of sublingual immunotherapy ( SLIT ) in patients with chronic rhinitis related to sensitization to house dust mites are still controversial Last years , in spite of increasing use of sublingual immunotherapy ( SLIT ) , not enough clinical studies have been published and its efficacy ought to be documented still more . For that purpose , 54 patients suffering seasonal rhinoconjunctivitis -- with or without asthma -- were allocated to either six month preseasonal SLIT with Lolium perenne extract ( n = 35 ) or to a control group ( n = 19 ) . In the following year , thirty from previously treated patients and 12 from former control group , received a nine-month pre-coseasonal SLIT . Skin ( SPT ) and conjunctival ( CPT ) allergen response were monitorized several times along the study . Either seric antibodies or intraseasonal eosinophil cationic protein ( ECP ) , as symptom , medication scores and peak nasal inspiratory flow ( PNIF ) were also assessed , fifty-five adverse reactions were recorded ( 0.7 % doses ) , although only four required treatment . No main changes in CPT , SPT and antibodies were detected . Nevertheless , during the first pollen season , treated patients needed less medication than their control counterparts ( p < 0.05 ) . In the second season , the twelve ex-control subjects also required fewer drugs than in the first one ( p < 0.01 ) . Moreover , the whole forty-two treated patients showed a lesser intraseasonal ECP than a reference set of grass-allergic individuals ( p < 0.05 ) . We conclude that Lolium perenne SLIT is well tolerated and induces fewer drug requirements during pollen season , being eosinophil activation additionally reduced Forty patients , monosensitized to Parietaria judaica with a clinical history of at least two years of rhinoconjunctivitis with or without asthma , were selected and r and omly allocated in two groups . According to an open controlled experimental plan , twenty patients were su bmi tted to sublingual immunotherapy ( SLIT ) with a solution of purified and biologically st and ardized extract of Parietaria judaica , following a preseasonal rush schedule . All patients , twenty belonging to the SLIT group and twenty belonging to the control group , were allowed to take authorized rescue drugs at need . At the end of the Parietaria pollen season . 15 patients for each group result ed to have complied with the criteria of the study . SLIT tolerance turned out to be excellent as no side effects were noticed in the group under treatment . No change could be detected in specific IgE and IgG4 in either group . According to the daily symptom and drug scores registered by each patient in a diary card , the SLIT group showed a statistically significant lower symptom score ( p = 0.032 ) and lower drug plus symptom score ( p = 0.037 ) during the peak pollen period ( May-June 1994 ) in comparison to the group treated only with symptomatic drugs . Moreover , 13 out of 15 patients su bmi tted to SLIT expressed a very favourable subjective opinion about the therapy and asked to continue the same treatment the following season . According to our results , the rush SLIT schedule , followed by maintenance during the pollen season , is simple , safe and effective for Parietaria pollen allergy and showed an excellent compliance BACKGROUND Seasonal allergic rhinitis is common and troublesome . Sublingual immunotherapy ( SLIT ) has been proposed as an alternative to injection immunotherapy and might offer some advantages if it were effective and practical in a community setting . OBJECTIVES To assess the efficacy and side-effect profile of SLIT in patients with summer hay fever uncontrolled on current st and ard medication . To assess the feasibility of delivering SLIT in a United Kingdom general practice setting . METHODS Double-blind , placebo-controlled study in 186 patients with severe summer hay fever identified from 16 United Kingdom general practice s. After a baseline year to ensure balanced groups , subjects were r and omized , and SLIT was given for 1 or 2 years and compared with placebo . The principal outcome measure was symptoms as recorded on diary cards . Secondary criteria were skin and conjunctival reactivity , allergen-specific IgE and IgG 4 , and the frequency and severity of adverse effects . RESULTS One hundred thirty-six subjects completed the study . After 1 year , no significant differences were found between actively treated subjects and the placebo group . After the second year of therapy , subjects who had received 2 years treatment were 6.8 times more likely to show a reduction in nose running ( P < .001 ) and 2.4 times more likely to have reduced sneezing ( P < .05 ) compared with subjects in the placebo group . Benefits for nasal blockage were found at the peak pollen season and were similar in both actively treated groups . CONCLUSION Sublingual immunotherapy can be given successfully and safely in the community . High-dose SLIT has beneficial effects on nasal symptoms during the peak pollen season in patients with severe seasonal allergic rhinitis . At least 2 years of treatment with SLIT is required to show a benefit Background : Sublingual immunotherapy ( SLIT ) has been demonstrated to be a viable alternative to injection immunotherapy . Administration of high doses of allergens to ensure efficacy has been shown to be well tolerated . The aim of the present study was the first step to address the issue of fast-induction regimens using various induction SLIT regimens in paediatric and adult patients . Methods : Sixty-four patients ( age range 5–46 years ) with grass pollen rhinoconjunctivitis were enrolled in an 8-month double-blind , placebo-controlled trial of SLIT . Sixty-three patients were r and omized to four groups and evaluated at the end of the study . One group received placebo ( n = 16 ) and the other three groups ( n = 47 ) received five grass pollen extracts according to three different induction regimens : regimen 1 starting with 3 IR tablets ( n = 15 ) , regimen 2 starting with 10 IR ( n = 16 ) and regimen 3 starting with 30 IR ( n = 16 ) . The maintenance phase was made with sublingual-swallow drops at the same concentration of 300 IR/ml for all the patients . Adverse events were recorded on diary cards . Results : During induction phase , 25/47 patients in the SLIT groups had adverse reactions in comparison to 2/16 patients in the placebo group ( p < 0.05 ) . The rate of adverse reactions was 33.3 % ( 11.8–61.6 ) ( 95 % CI ) for regimen 1 , 31.3 % ( 11.0–58.7 ) for regimen 2 , 43.8 % ( 19.8–70.1 ) for regimen 3 and 12.5 % ( 1.6–38.3 ) for placebo . Fifty-seven reactions were local reactions involving the oral region ( 54 SLIT , 3 placebo ) and 13 were systemic reactions ( all in the SLIT groups ) . 11/13 reactions were mild ( gastrointestinal disorders , rhinoconjunctivitis ) , 1/13 consisted of moderate asthma and 1/13 consisted of severe abdominal pain . No urticaria , angioedema or life-threatening events were observed . Conclusions : These preliminary data showed that various induction regimens for SLIT are generally well tolerated and could allow a fast build-up phase of SLIT BACKGROUND non-injective routes of immunotherapy in respiratory allergy have being proposed as an alternative to conventional immunotherapy . We carried out a study to evaluate the clinical efficacy and effects sublingual immunotherapy ( SLIT ) in patient with Cupressaceae pollen respiratory allergy . METHODS twenty patients with Cupressaceae pollen ( C. sempervirens ) rhinoconjunctivitis , mild asthma or both were r and omly chosen for sublingual immunotherapy ( 10 patients ) or placebo treatment ( 10 patients ) using a double blind placebo controlled technique . We have used an extract of Cupressus arizonica because of its better stability in solution and its crossreactivity with Cupressus sempervirens . The patients underwent treatment for 12 months ( from april 1999 to april 2000 ) . Symptoms and drug scores as well as nasal provocation tests were recorded . The pollen counts were carried out , during all the same period . RESULTS we found significantly lower symptom scores ( p < 0.05 ) and drug consumption scores ( p < 0.05 ) in the immunotherapy group than in the placebo group , during the pollen season , after the first year of therapy . Besides threshold of allergen reactivity in nasal provocation tests was increased in the active group ( p < 0.01 ) . No untoward reactions have been observed . CONCLUSIONS SLIT with Cupressus arizonica ( pollen extracts ) produced , after one year treatment , a significant improvement of allergic symptoms and a decrease of drug consumption scores and allergen-specific nasal reactivity . SLIT with Cupressus arizonica appeared to be effective and safe in the treatment of Cupressaceae pollen respiratory allergy Grass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit . Immunotherapy may act by altering the local nasal mucosal T helper type 2 ( Th2 ) to type 1 ( Th1 ) cytokine balance either by down-regulation and /or immune deviation of T-lymphocyte responses . There is controversy as to whether these changes are detectable in peripheral blood . We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after immunotherapy . In a double-blind trial of grass pollen immunotherapy , nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of immunotherapy . Placebo-treated patients showed a seasonal increase in CD3(+ ) T cells ( P = 0.02 ) and in interleukin-5 ( IL-5 ) mRNA(+ ) cells ( P = 0.03 ) and no change in interferon-gamma ( IFN-gamma ) mRNA(+ ) cells ( P = 0.2 ) in the nasal mucosa . In contrast , in the immunotherapy-treated group , there were no changes in the number of CD3(+ ) T cells ( P = 0.3 ) and IL-5 mRNA+ cells ( P = 0.2 ) but a significant increase in the number of IFN-gamma mRNA(+ ) cells ( P = 0.03 ) . Furthermore , clinical improvement in the immunotherapy-treated group was accompanied by a seasonal increase in the ratio of IFN-gamma to IL-5 mRNA(+ ) cells in the nasal mucosa ( P = 0.03 ) . In contrast , there were no significant changes in peripheral T-cell proliferative responses or cytokine production for IFN-gamma or IL-5 in response to grass pollen either within or between the two treatment groups . We conclude that successful grass pollen immunotherapy was associated with an increase in the ratio of IFN-gamma to IL-5 mRNA(+ ) cells in the nasal mucosa , whereas these changes were not reflected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment Background : The safety and efficacy of sublingual‐swallow immunotherapy ( SLIT ) in rhinitis caused by house‐dust mite were evaluated in a double‐blind , placebo‐controlled study including 75 patients for 24 months Background : Both sublingual allergen‐specific immunotherapy ( SLIT ) and subcutaneous immunotherapy ( SCIT ) have a documented clinical efficacy , but only few comparative studies have been performed Background : Recent studies have demonstrated the efficacy of sublingual‐swallow immunotherapy ( SLIT ) in seasonal and perennial rhinitis . Sublingual administration of solutions is not convenient for all patients . The aim of the study was to evaluate the efficacy and safety of immunotherapy administered sublingually , initially as drops , and then as tablets during maintenance therapy BACKGROUND The efficacy of therapy with sublingual allergen extracts is unproven . OBJECTIVE To evaluate the clinical and immunologic outcome of sublingual immunotherapy and to compare the results with subcutaneous immunotherapy and placebo in 36 patients with rhinitis and asthma due to mite allergy . METHOD Thirty-six patients with rhinitis and asthma due to mite allergy were r and omly divided into three groups in order to receive subcutaneous injections with allergenic extracts , sublingual drops with solutions of purified st and ardized allergen preparations , or sublingual placebo for a period of 1 year . Assessment of clinical and immunologic efficacy included symptom and medication scores , methacholine provocation tests , skin prick tests , and specific IgE and IgG4 antibody concentrations . RESULTS Subcutaneous immunotherapy for both rhinitis and asthma was clinical ly effective . Patients treated with sublingual immunotherapy had decreased rhinitis symptoms ( P < .01 ) but no change in asthma scores . Medication scores significantly decreased in both actively treated groups ( P < .01 ) at the first year compared with baseline . When skin prick tests were evaluated , the subcutaneously treated group had a significant decrease in the wheal diameter of D. pteronyssinus ( P < .01 ) , D. farinae ( P < .05 ) , and histamine ( P < .05 ) while other two groups showed no difference . There was no significant change in methacholine PC20 values in all groups at the end of the first year when compared with baseline . No change in D. pteronyssinus and D. farinae specific IgE levels were observed ; however , specific IgG4 concentrations were significantly higher than baseline both in sublingual and subcutaneous immunotherapy groups ( P < .05 ) after 1 year immunotherapy . No significant difference was obtained in any of these parameters in the placebo group . CONCLUSION Sublingual immunotherapy may be effective in patients with allergic rhinitis . Further , we believe it is a potential therapy for allergic asthmatic patients . The clinical usefulness of this form of immunotherapy ( when administered to larger study groups for a longer time ) and the mechanisms underlying its immunologic effect deserve additional studies Background : We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and /or rhinitis and /or rhinoconjunctivitis due to grass pollen BACKGROUND The local ( noninjection ) routes of immunotherapy are presently regarded as viable therapeutic options for respiratory allergy , and their mechanisms of action are currently undergoing investigation . OBJECTIVE We evaluated the clinical efficacy of a preseasonal rush sublingual-swallow immunotherapy and its effects on allergic inflammation in patients with seasonal rhinoconjunctivitis caused by Parietaria species . METHODS Thirty patients with Parietaria species-induced rhinoconjunctivitis ( 13 with mild intermittent asthma ) were r and omly assigned sublingual-swallow immunotherapy or placebo in a rush preseasonal course . We assessed the seasonal symptom-drug intake score by diary card and the inflammatory infiltration and the intercellular adhesion molecule 1 expression on nasal epithelium after specific allergenic challenge before and after treatment . RESULTS The investigated immunotherapy was well tolerated , and no side effects were recorded . A significant reduction of the symptom score ( P = .016 ) and drug intake score ( P = . 008 ) after immunotherapy was observed only in the active group . A decrease of the cumulative score was observed also in the placebo group ( P = .046 ) , but the significance was clearly higher ( P = .006 ) in the active group . In the active group a reduction of neutrophils ( P = .001 ) , eosinophils ( P = .01 ) , and intercellular adhesion molecule 1 expression ( P = .04 ) after specific nasal challenge was also detected . CONCLUSION The present results suggest that this sublingual-swallow immunotherapy administered through a rush schedule is clinical ly effective and safe and that it decreases the immune-mediated inflammatory responses to the allergen Fifty‐eight patients with well‐documented history of seasonal rhinoconjunctivitis caused by grass pollens were allocated r and omly on a double‐blind basis to receive either sublingual therapy with a solution of purified , st and ardized allergen preparation ( Stallergenes ) or a matched placebo for 17 weeks . The assessment of the effect of oral immunotherapy , done with drops of five‐grass allergen extract , was on the clinical symptoms and on the medication score of the authorized rescue treatments . The actively treated patients had significantly ( P<0.05 to P<0.01 ) fewer symptoms of rhinitis ( sneezing and rhinorrhea ) and of conjunctivitis ( redness and tears ) during the pollen season than the placebo group . Consumption of nasal solution of sodium cromoglycate and of betamethasone and dexchlorpheniramine was significantly less in the desensitized group ( P<0.01 ) . Side‐effects were negligible . This study concludes that perlingual immunotherapy with grass pollen extract in grass‐pollen‐sensitive seasonal hay fever and conjunctivitis patients is effective , easy to perform , inexpensive , and safe To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results |
12,455 | 22,453,771 | RESULTS The actuated ankle-foot orthoses currently available are characterized by several combinations of an actuator and a control mechanism .
Both the actuator and the control strategy substantially influence human-machine interaction and therefore the potential of the device to assist in modifying locomotor function and potentially modify the underlying motor control mechanisms .
CONCLUSION Due to small sample sizes , limited studies in patients with spinal cord injury , and limitations in study design , it is difficult to draw firm conclusions on the effect of different types of actuated ankle-foot orthoses .
Based on the limited data available , pneumatic artificial muscles in combination with proportional myoelectric control are suggested to have the potential to meet most of the preconditions to restore the attributes of normal gait and therefore facilitate neuroplasticity | OBJECTIVE To provide an overview of robot-assisted rehabilitation devices developed for actuation of the ankle-foot complex and their ability to influence the attributes of normal gait in patients with spinal cord injury . | Recent research has suggested that enhanced retraining for stroke patients using haptics ( robotic forces ) and graphics ( visual display ) to generate a practice environment that can artificially enhance error rather than reducing it , can stimulate new learning and foster accelerated recovery . We present an evaluation of early results of this novel post-stroke robotic-aided therapy trial that incorporates these ideas in a large VR system and simultaneously employs the patient , the therapist , and the technology to accomplish effective therapy Background . The 10-meter walk test and 6-minute walk test are increasingly used to evaluate the recovery of walking in patients with incomplete spinal cord injury . So far , there is no evidence whether the application of different walking distances provides complementary information about ambulatory capacity in patients with incomplete spinal cord injury . Studies about testing preferred and maximum speeds in subjects with incomplete spinal cord injury are lacking . Objective . To determine whether the combined testing of short and long distances as well as preferred and maximum speeds provides additional information about walking capacity in subjects with incomplete spinal cord injury . Methods . Depending on the objective , the subjects with incomplete spinal cord injury and age-matched control subjects had to perform the 10-meter walk test or 6-minute walk test at preferred and /or maximum walking speed . Results . During recovery , the preferred walking speed increased but did not differ when assessed during short or long distances in 51 subjects with incomplete spinal cord injury at 1 , 3 , and 6 months after injury ( mean and SD , 6-minute walk test : 0.37 ± 0.52 , 0.87 ± 0.56 , and 1.14 ± 0.52 ms —1 ; 10-meter walk test : 0.40 ± 0.53 , 0.88 ± 0.51 , and 1.12 ± 0.51 ms—1 , respectively ) . In 18 subjects with incomplete spinal cord injury , both preferred and maximum walking speeds assessed with the 10-meter walk test predicted the walking speeds of the 6-minute walk test well . Subjects with incomplete spinal cord injury prefer to walk closer to their maximum walking speed ( 74 % ± 10 % ) compared to control subjects ( 59 % ± 8 % ) . Conclusions . The velocity used for the 6-minute walking distance and the 10-meter walking speed provides comparable information in patients with incomplete spinal cord injury who can perform both tests . However , tests of the preferred and maximum walking speed add information about walking capacity . Due to the easier applicability of the 10-meter walk test in the clinical setting , the authors suggest performing this test at the preferred and maximum speeds for the assessment of walking capacity by 1 month after incomplete spinal cord injury Fifty individuals with incomplete tetraplegia due to trauma underwent serial prospect i ve examinations to quantify motor and sensory recovery . None of 5 patients who were motor complete with the presence of sacral ( S4-S5 ) sharp/dull touch sensation unilaterally recovered any lower extremity motor function . However , in 8 motor complete subjects having bilateral sacral sharp/dull sensation present , the mean lower extremity motor score increased to 12.1 + /- 7.8 at 1 year . In 3 of the 8 cases , functional ( > or = 3/5 ) recovery was seen in some muscles at 1 year . Though mean upper and lower extremity ASIA Motor Scores increased significantly ( p < .001 ) between 1 month and 1 year for the entire sample , the annualized rate of motor recovery rapidly declined in the first 6 months and then subsequently approached plateau . Eighty-seven percent ( 20 of 23 ) of patients having a lower extremity motor score > or = 10 at 1 month were community ambulators using crutches and orthoses at 1 year follow-up We used a lower limb robotic exoskeleton controlled by the wearer 's muscle activity to study human locomotor adaptation to disrupted muscular coordination . Ten healthy subjects walked while wearing a pneumatically powered ankle exoskeleton on one limb that effectively increased plantar flexor strength of the soleus muscle . Soleus electromyography amplitude controlled plantar flexion assistance from the exoskeleton in real time . We hypothesized that subjects ' gait kinematics would be initially distorted by the added exoskeleton power , but that subjects would reduce soleus muscle recruitment with practice to return to gait kinematics more similar to normal . We also examined the ability of subjects to recall their adapted motor pattern for exoskeleton walking by testing subjects on two separate sessions , 3 days apart . The mechanical power added by the exoskeleton greatly perturbed ankle joint movements at first , causing subjects to walk with significantly increased plantar flexion during stance . With practice , subjects reduced soleus recruitment by approximately 35 % and learned to use the exoskeleton to perform almost exclusively positive work about the ankle . Subjects demonstrated the ability to retain the adapted locomotor pattern between testing sessions as evidence d by similar muscle activity , kinematic and kinetic patterns between the end of the first test day and the beginning of the second . These results demonstrate that robotic exoskeletons controlled by muscle activity could be useful tools for testing neural mechanisms of human locomotor adaptation An active ankle-foot orthoses ( AAFO ) is presented where the impedance of the orthotic joint is modulated throughout the walking cycle to treat drop-foot gait . During controlled plantar flexion , a biomimetic torsional spring control is applied where orthotic joint stiffness is actively adjusted to minimize forefoot collisions with the ground . Throughout late stance , joint impedance is minimized so as not to impede powered plantar flexion movements , and during the swing phase , a torsional spring-damper control lifts the foot to provide toe clearance . To assess the clinical effects of variable-impedance control , kinetic and kinematic gait data were collected on two drop-foot participants wearing the AAFO . For each participant , zero , constant , and variable impedance control strategies were evaluated and the results were compared to the mechanics of three age , weight , and height matched normals . We find that actively adjusting joint impedance reduces the occurrence of slap foot allows greater powered plantar flexion and provides for less kinematic difference during swing when compared to normals . These results indicate that a variable-impedance orthosis may have certain clinical benefits for the treatment of drop-foot gait compared to conventional ankle-foot orthoses having zero or constant stiffness joint behaviors The Spinal Cord Independence Measure ( SCIM ) is a new disability scale developed specifically for patients with spinal cord lesions in order to make the functional assessment s of patients with paraplegia or tetraplegia more sensitive to changes . The SCIM includes the following areas of function : self-care ( subscore 0 – 20 ) , respiration and sphincter management ( 0 – 40 ) and mobility ( 0 – 40 ) . Each area is scored according to its proportional weight in these patients ' general activity . The final score ranges from 0 to 100 . This study was performed to evaluate the reliability of the SCIM and its sensitivity to functional changes in spinal cord lesion patients compared with the Functional Independence Measure ( FIM ) . Thirty patients were included . Scores were recorded one week after admission and thereafter every month during hospitalization . Each area of function was assessed by a pair of staff members from the relevant discipline . The comparison of scores between each pair of raters revealed a remarkable consistency ( r=0.91 – 0.99 ; P<0.0001 ; slope≈1 ; constant≈0 ) . The total SCIM score ( mean=51 , SD=21 ) was lower than the total FIM score ( mean=87 , SD=23 ) owing to the difference in scale range structure and the relatively high cognitive scores of our patients ; however , a relationship was noted between the scores of both scales ( r=0.85 , P<0.01 ) . The SCIM was more sensitive than the FIM to changes in function of spinal cord lesion patients : the SCIM detected all the functional changes detected by the FIM total scoring , but the FIM missed 26 % of the changes detected by the SCIM total scoring . The mean difference between consecutive scores was higher for the SCIM ( P<0.01 ) . We conclude that the SCIM is a reliable disability scale and is more sensitive to changes in function in spinal cord lesion patients than the FIM . The SCIM when administered by a multidisciplinary team , may be a useful instrument for assessing changes in everyday performance in patients with spinal cord lesion |
12,456 | 24,085,594 | The most effective interventions applied a tailored approach to the type of PA and used telephone contact to provide feedback and to support changes in PA levels .
We found consistent evidence to support the effectiveness of remote and web 2.0 interventions for promoting PA .
These interventions have positive , moderate sized effects on increasing self-reported PA and measured cardio-respiratory fitness , at least at 12 months .
The effectiveness of these interventions was supported by moderate and high quality studies . | BACKGROUND Remote and web 2.0 interventions for promoting physical activity ( PA ) are becoming increasingly popular but their ability to achieve long term changes are unknown .
OBJECTIVES To compare the effectiveness of remote and web 2.0 interventions for PA promotion in community dwelling adults ( aged 16 years and above ) with a control group exposed to placebo or no or minimal intervention . | Abstract Objective : To evaluate the effectiveness of combinations of three methods to promote physical activity . Design : R and omised controlled trial . Baseline assessment with post-intervention follow up at 12 weeks and 1 year . Setting : One urban general practice , 1995 - 7 . Participants : 523 adults aged 40 to 64 years , r and omised to four intervention groups and a control group . Interventions : Brief ( one interview ) or intensive ( six interviews over 12 weeks ) motivational interviewing based on the stages of change model of behaviour change , with or without financial incentive ( 30 vouchers entitling free access to leisure facilities ) . Main outcome measures : Physical activity score ; sessions of moderate and vigorous activity in the preceding four weeks . Results : Response rate was 81 % at 12 weeks and 85 % at one year . More participants in the intervention group reported increased physical activity scores at 12 weeks than controls ( 38 % v 16 % , difference 22 % , 95 % confidence interval for difference 13 % to 32 % ) , with a 55 % increase observed in those offered six interviews plus vouchers . Vigorous activity increased in 29 % of intervention participants and 11 % of controls ( difference 18 % , 10 % to 26 % ) , but differences between the intervention groups were not significant . Short term increases in activity were not sustained , regardless of intensity of intervention . Conclusions : The most effective intervention for promoting adoption of exercise was the most intensive . Even this did not promote long term adherence to exercise . Brief interventions promoting physical activity that are used by many schemes in the United Kingdom are of question able effectiveness . Key messages Schemes promoting physical activity are currently popular in general practice in Britain , but few have been rigorously evaluated and their effectiveness is unknown . In this study , the most effective intervention for promoting adoption of physical activity was the most intensive , involving six motivational interviews and a financial incentive A comparatively brief intervention ( one interview ) was only effective in the short term in around a third of participants Short term increases in physical activity were not maintained at one year follow up and even the most intensive intervention was ineffective in promoting long term adherence to increased physical activity . National and local government , health authorities , and primary healthcare teams should be cautious about current and future expenditure on , and implementation of , exercise prescription or referral BACKGROUND Using peer volunteers as delivery agents may improve translation of evidence -based physical activity promotion programs for older adults . This study examined whether tailored support from older peer volunteers could improve initiation and long-term maintenance of physical activity behavior . METHODS Participants were r and omized to 2 16-week , group-based programs : ( 1 ) peer-delivered , theory-based support for physical activity behavior change ; or ( 2 ) an intervention typically available in community setting s ( basic education , gym membership , and pedometer for self-monitoring ) , attention-matched with health education . Moderate-to-vigorous physical activity ( MVPA ) was assessed via daily self-report logs at baseline , at the end of the intervention ( 16 weeks ) , and at follow-up ( 18 months ) , with accelerometry validation ( RT3 ) in a r and om sub sample . RESULTS Seven peer volunteers and 81 sedentary adults were recruited . Retention at the end of the trial was 85 % and follow-up at 18 months was 61 % . Using intent-to-treat analyses , at 16 weeks , both groups had similar significant improvements in MVPA . At 18 months , the group supplemented with peer support had significantly more MVPA . CONCLUSIONS Trained peer volunteers may enhance long-term maintenance of physical activity gains from a community-based intervention . This approach has great potential to be adapted and delivered inexpensively in community setting Background Following an extensive recruitment campaign , a 16-week lunchtime intervention to increase walking was implemented with insufficiently physically active University employees to examine programme feasibility and the effects of the programme in increasing walking behaviour , and in improving well-being and work performance . Methods / design A feasibility study in which participants were r and omised to an immediate treatment or a delayed treatment control ( to start at 10 weeks ) group . For the first ten weeks of the intervention , participants took part in three facilitator-led group walks per week each of thirty minutes duration and were challenged to accumulate another sixty minutes of walking during the weekends . In the second phase of the intervention , the organised group walks ceased to be offered and participants were encouraged to self-organise their walks . Motivational principles were employed using contemporary motivational theory . Outcome measures ( including self-reported walking , step counts , cardiovascular fitness , general and work-related well-being and work performance ) were assessed at baseline , at the end of the 16-week intervention and ( for some ) four months after the end of the intervention . Process and outcome assessment s were also taken throughout , and following , the intervention . Discussion The results of the intervention will determine the feasibility of implementing a lunchtime walking programme to increase walking behaviour , well-being and performance in sedentary employees . If successful , there is scope to implement definitive trials across a range of worksites with the aim of improving both employee and organisational health . Trial registration Current Controlled Trials IS RCT N81504663 Mediation analyses in faith-based physical activity ( PA ) interventions targeting African-American adults are lacking . The purpose of this study was to examine the psychosocial mediators of a faith-based PA intervention with African-American adults . Churches were r and omly assigned to receive immediate or delayed ( 1-year later ) training in PA program implementation . A sub sample of participants from r and omly selected churches took part in telephone surveys at baseline and at 1 year . The primary outcome was percentage of participants meeting PA recommendations . MacKinnon 's product of coefficients was used to test for mediation . Participants ( n = 418 ) from 20 churches completed the baseline and 1-year follow-up surveys . There were no statistically significant changes in PA behavior at 1 year . The intervention had a marginally significant effect on increasing the amount of instrumental church support received by church members . However , none of the psychosocial variables tested were found to be significant mediators of the intervention . Mediation analyses provided insight into potential reasons as to why the Health-e-AME intervention did not change PA . The intervention did not successfully change the targeted mediators hypothesized to change PA . Potential reasons for these shortcomings as well as issues to address in future faith-based studies are discussed This paper reports on the cost-effectiveness of pedometer-based versus time-based Green Prescriptions in improving physical activity and health-related quality of life ( EQ-5D ) in a r and omised controlled trial of 330 low-active , community-based adults aged 65 years and over . Costs , measured in $ NZ ( NZ$1=A$0.83 , December 2008 ) , comprised public and private health care costs plus exercise-related personal expenditure . Based on intention-to-treat data at 12-month follow up , the pedometer group showed a greater increase in weekly leisure walking ( 50.6 versus 28.1min for the time-based group , adjusted means , P=0.03 ) . There were no significant between-group differences in costs . The incremental cost-effectiveness ratios , for the pedometer-based versus time-based Green Prescription , per 30min of weekly leisure walking and per quality -adjusted life year were , ( i ) when including only community care costs , $ 115 and $ 3105 , ( ii ) when including only exercise and community care costs , $ 130 and $ 3500 , and ( iii ) for all costs , -$185 and -$4999 , respectively . The cost-effectiveness acceptability curves showed that the pedometer-based compared with the time-based Green Prescription was statistically cost-effective , for the above cost categories , at the following quality -adjusted life year thresholds : ( i ) $ 30000 ; ( ii ) $ 30500 ; and ( iii ) $ 16500 . The additional program cost of converting one sedentary adult to an active state over a 12-month period was $ 667 . The outcomes suggest the pedometer-based Green Prescription may be cost-effective in increasing physical activity and health-related quality of life over 12 months in previously low-active older adults BACKGROUND Physical activity promotion is a priority , but contribution of physicians ' interventions is unclear . The effectiveness of the PEPAF ( " Experimental Program for Physical Activity Promotion " ) , which was implemented exclusively by physicians in routine primary care from October 2003 to December 2004 , was assessed . METHODS Fifty-six Spanish family physicians were r and omized to either the intervention ( n = 29 ) or st and ard care ( n = 27 ) arm of the trial . The physicians recruited 4317 physically inactive patients ( 2248 for intervention and 2069 for control protocol s ) from a systematic sample after assessing their physical activity in routine practice . Intervention physicians provided advice to all patients and a physical activity prescription to the subgroup attending an additional appointment ( 30 % ) . The main outcome measure was the change in physical activity measured by blinded nurses using the 7-Day Physical Activity Recall . Secondary outcomes included cardiorespiratory fitness and health-related quality of life . RESULTS At 6 months , intervention patients increased physical activity more than controls ( adjusted difference , 18 min/wk [ 95 % confidence interval , 6 - 31 min/wk ] ; metabolic equivalent tasks x hours per week , 1.3 [ 95 % CI , 0.4 - 2.2 ] ) . The proportion of the population achieving minimal physical activity recommendations was 3.9 % higher in the intervention group ( 1.2%-6.9 % ; number needed to treat , 26 ) . No differences were found in secondary outcomes . The effect of intervention was positively modified in subjects older than 50 years ( P < or = .01 ) and in the prescription subgroup ( P < .001 ) . CONCLUSIONS Family physicians were effective for increasing physical activity of primary care patients . Overall clinical effect was small but relevant for population public health . Within the intervention program , clinical ly relevant effects were seen in patients receiving a physical activity prescription . Trial Registration clinical trials.gov Identifier : NCT00131079 Background Limited data are available on the development , implementation and evaluation processes of physical activity promotion programmes among older adults . More integrative insights into interventions describing the planned systematic development , implementation and evaluation are needed . Methods and design The purpose of this study is to give an integrative insight into the development of the Active plus programme applying the six-step Intervention Mapping protocol . The Active plus programme consisted of two theory- and evidence -based tailored physical activity promotion interventions , both comprising three tailored letters delivered over four months and aim ed at raising awareness of insufficient physical activity , and stimulating physical activity initiation and maintenance among the over-fifties . The first intervention , the basic tailored intervention , provided tailored letters that intervened on the psychosocial determinants of physical activity . The second intervention , the intervention plus , provided the same tailored information but additionally provided tailored information about physical activity opportunities in the specific environment in which the older adults lived . This environment-based component also provided access to a forum and e-buddy system on a website . A plan for implementation and evaluation is also described . Discussion The planned development of the Active plus programme result ed in two theory- and evidence -based tailored physical activity interventions targeted at the over-fifties . Trial Registration Dutch Trial Register NTR OBJECTIVE We evaluate the 6-month efficacy of Keep Active Minnesota , a phone- and mail-based physical activity maintenance intervention design ed for use with adults age 50 to 70 years who have increased their physical activity within the past year . METHOD Participants ( N=1049 ) recruited in 2004 and 2005 from one large managed-care organization in Minnesota were r and omly assigned to either treatment ( N=523 ) or usual care ( N=526 ) with physical activity assessed using the Community Healthy Activities Model Program for Seniors question naire , and expressed as kcal/week expenditures . RESULTS Total physical activity at baseline was similar for treatment and usual care participants ( p<0.44 ) as was moderate/vigorous physical activity ( p<0.21 ) . Maintenance of physical activity was higher among treatment participants whose mean 6-month change in total kcal/week energy expenditure was -91 , compared to -683 for usual care participants ( p<0.002 ) . Mean 6-month change in kcal/week expenditure in moderate or vigorous activities was -49 for treatment participants , compared to -612 for usual care participants ( p<0.001 ) . CONCLUSIONS This phone- and mail-based physical activity maintenance intervention is efficacious at maintaining physical activity at 6 months Background Scotl and has a policy aim ed at increasing physical activity levels in the population , but evidence on how to achieve this is still developing . Studies that focus on encouraging real world participants to start physical activity in their setting s are needed . The Walking for Well-being in the West study was design ed to assess the effectiveness of a pedometer-based walking programme in combination with physical activity consultation . The study was multi-disciplinary and based in the community . Walking for Well-being in the West investigated whether Scottish men and women , who were not achieving the current physical activity recommendation , increased and maintained walking behaviour over a 12 month period . This paper outlines the rationale and design of this innovative and pragmatic study . Methods Participants were r and omised into two groups : Group 1 : Intervention ( pedometer-based walking programme combined with a series of physical activity consultations ) ; Group 2 : Waiting list control for 12 weeks ( followed by minimal pedometer-based intervention ) . Physical activity ( primary outcome ) was measured using pedometer step counts ( 7 day ) and the International Physical Activity Question naire ( long version ) . Psychological processes were measured using question naires relating to the Transtheoretical Model of Behaviour Change , mood ( Positive and Negative Affect Schedule ) and quality of life ( Euroqol EQ-5D instrument ) . Physiological measures included anthropometric and metabolic outcomes . Environmental influences were assessed subjectively ( Neighbourhood Quality of Life Survey ) and objective ly ( neighbourhood audit tool and GIS mapping ) . The qualitative evaluation employed observation , semi-structured interviews and focus groups . A supplementary study undertook an economic evaluation . Discussion Data analysis is on-going . Walking for Well-being in the West will demonstrate if a pedometer based walking programme , in combination with physical activity consultation results in a sustainable increase in walking behaviour in this sample of Scottish adults over a 12 month period . The study will examine the complex relationships between behavioural change , health consequences and the role of the environment , in conjunction with the cost effectiveness of this approach and a detailed insight into the participants ' experiences of the intervention . Trial registration Current Controlled Trials IS RCT Background Recent systematic review s have suggested that pedometers may be effective motivational tools to promote walking . However , studies tend to be of a relatively short duration , with small clinical based sample s. Further research is required to demonstrate their effectiveness in adequately powered , community based studies . Objective Using a r and omized controlled trial design , this study assessed the impact of a 12-week graduated pedometer-based walking intervention on daily step-counts , self-reported physical activity and health outcomes in a Scottish community sample not meeting current physical activity recommendations . MethodS ixty-three women and 16 men ( 49.2 years ± 8.8 ) were r and omly assigned to either an intervention ( physical activity consultation and 12-week pedometer-based walking program ) or control ( no action ) group . Measures for step-counts , 7-day physical activity recall , affect , quality of life ( n = 79 ) , body mass , BMI , % body fat , waist and hip circumference ( n = 76 ) , systolic/diastolic blood pressure , total cholesterol and HDL cholesterol ( n = 66 ) were taken at baseline and week 12 . Analyses were performed on an intention to treat basis using 2-way mixed factorial analyses of variance for parametric data and Mann Whitney and Wilcoxon tests for non-parametric data . Results Significant increases were found in the intervention group for step-counts ( p < .001 ) , time spent in leisure walking ( p = .02 ) and positive affect ( p = .027 ) . Significant decreases were found in this group for time spent in weekday ( p = .003 ) , weekend ( p = .001 ) and total sitting ( p = .001 ) with no corresponding changes in the control group . No significant changes in any other health outcomes were found in either group . In comparison with the control group at week 12 , the intervention group reported a significantly greater number of minutes spent in leisure time ( p = .008 ) , occupational ( p = .045 ) and total walking ( p = .03 ) , and significantly fewer minutes in time spent in weekend ( p = .003 ) and total sitting ( p = .022 ) . Conclusion A pedometer-based walking program , incorporating a physical activity consultation , is effective in promoting walking and improving positive affect over 12 weeks in community based individuals . The discussion examines possible explanations for the lack of significant changes in health outcomes . Continued follow-up of this study will examine adherence to the intervention and possible result ing effects on health outcomes Background Ageing is associated with a decrease in physical activity . This decrease particularly occurs during specific transitional life stages . Especially during adolescence and young adulthood a steep decrease in physical activity is observed . Inactive people are often not aware of their inactivity . Providing feedback on the actual physical activity level by an activity monitor can increase awareness and may in combination with an individually tailored physical activity advice stimulate a physically active lifestyle . Methods In a r and omized controlled trial the effectiveness of providing an activity monitor in combination with a personal physical activity advice through the Internet will be examined . Outcome measures are level of physical activity , determinants of physical activity , quality of life , empowerment , aerobic fitness and body composition . Participants are relatively inactive adolescents and young adults who are measured at baseline , after 3 months intervention and 5 months after the end of the intervention . In addition , facilitating and hindering factors for implementation of the intervention will be investigated . Discussion The use of a personal activity monitor in combination with web-based assisted individually tailored health promotion offers a good opportunity to work interactively with large groups of adolescents and young adults and provide them with advice based on their actual activity level . It has great potential to motivate people to change their behaviour and to our knowledge has not been evaluated before Background Grade d health benefits of physical activity have been demonstrated for the reduction of coronary heart disease , some cancers , and type-2 diabetes , and for injury reduction and improvements in mental health . Older adults are particularly at risk of physical inactivity , and would greatly benefit from successful targeted physical activity interventions . Methods / Design The Healthy Steps study is a 12-month r and omized controlled trial comparing the efficacy of a pedometer-based Green Prescription with the conventional time-based Green Prescription in increasing and maintaining physical activity levels in low-active adults over 65 years of age . The Green Prescription interventions involve a primary care physical activity prescription with 3 follow-up telephone counselling sessions delivered by trained physical activity counsellors over 3 months . Those in the pedometer group received a pedometer and counselling based around increasing steps that can be monitored on the pedometer , while those in the st and ard Green Prescription group received counselling using time-based goals . Baseline , 3 month ( end of intervention ) , and 12 month measures were assessed in face-to-face home visits with outcomes measures being physical activity ( Auckl and Heart Study Physical Activity Question naire ) , quality of life ( SF-36 and EQ-5D ) , depressive symptoms ( Geriatric Depression Scale ) , blood pressure , weight status , functional status ( gait speed , chair st and s , and t and em balance test ) and falls and adverse events ( self-report ) . Utilisation of health services was assessed for the economic evaluation carried out alongside this trial . As well , a process evaluation of the interventions and an examination of barriers and motives for physical activity in the sample were conducted . The perceptions of primary care physicians in relation to delivering physical activity counselling were also assessed . Discussion The findings from the Healthy Steps trial are due in late 2009 . If successful in improving physical activity in older adults , the pedometer-based Green Prescription could assist in reducing utilisation of health services and improve cardiovascular health and reduction of risk for a range of non-communicable lifestyles diseases . Trial registration Australian and New Zeal and Clinical Trials Registry INTRODUCTION Project Graduate Ready for Activity Daily evaluated a program to promote physical activity through the transition of university graduation in a r and omized controlled trial . METHODS Three hundred thirty-eight university seniors participated in either a cognitive-behavioral intervention course or a knowledge-oriented general health course during the semester before graduation . Behaviorally oriented phone and mail follow-up was delivered to the intervention group for 18 months . Physical activity outcomes and mediating variables were assessed at baseline , 1 and 2 years ( 93 % retention rate ) . RESULTS There were no significant intervention effects on physical activity outcomes at 2 years for either men or women . Experiential and behavioral processes of change were significantly improved for intervention women over 2 years . CONCLUSIONS Despite excellent participation in a theoretically based , well-attended intervention , few long-term effects on physical activity or its mediators were found . Additional research is needed to determine optimal interventions for physical activity and to vali date or alter current behavior change theory Background Pedometers provide a simple , cost effective means of motivating individuals to increase walking yet few studies have considered if short term changes in walking behaviour can be maintained in the long-term . The role of physical activity consultations in such interventions is unclear . The purpose of this study was to assess the sustainability of pedometer-based interventions and empirically examine the role of physical activity consultations using long-term results of a community-based walking study . Methods 79 low active Scottish men and women ( 63 women and 16 men ) from the Walking for Wellbeing in the West intervention study were r and omly assigned to receive either : Group 1 ; pedometer-based walking programme plus physical activity consultations or Group 2 ; pedometer-based walking programme and minimal advice . Step counts ( Omron HJ-109E Step-O-Meter pedometer ) , 7 day recall of physical activity ( IPAQ long ) , mood ( PANAS ) and quality of life ( EuroQol EQ-5D ) were assessed pre-intervention and 12 , 24 and 48 weeks after receiving the intervention . Body mass , body mass index and waist and hip circumference were assessed pre-intervention and 12 and 24 weeks after receiving the intervention . Analyses were performed on an intention to treat basis ( baseline value carried forward for missing data ) using mixed-factorial ANOVAs and follow-up t-tests . Results A significant main effect of time ( p < 0.001 ) was found for step-counts attributable to significant increases in steps/day between : pre-intervention ( M = 6941 , SD = 3047 ) and 12 weeks ( M = 9327 , SD = 4136 ) , t(78 ) = - 6.52 , p < 0.001 , d = 0.66 ; pre-intervention and 24 weeks ( M = 8804 , SD = 4145 ) , t(78 ) = - 4.82 , p < 0.001 , d = 0.52 ; and pre-intervention and 48 weeks ( M = 8450 , SD = 3855 ) , t(78 ) = - 4.15 , p < 0.001 , d = 0.44 . Significant effects were found for several variables of self-reported physical activity , mood and quality of life and are discussed . No other significant effects in health related outcomes were found . Conclusion Both interventions successfully increased and maintained step counts over 12 months . Physical activity consultations may encourage individuals to be active in other ways beyond walking and to reduce sitting time . Trial Registration NumberCurrent Controlled Trials Ltd IS RCT BACKGROUND Few primary care physicians routinely counsel for exercise , despite the benefits of physical activity and the high prevalence of inactivity . The objective of this study is to assess the effectiveness of Physician-Based Assessment and Counseling for Exercise ( PACE ) , a brief , behavior-based tool for primary care providers counseling healthy adults . METHODS This study is a r and omized controlled trial of 812 patients age 30 years or older registered for well visits at 32 primary care physician offices at a staff model health maintenance organization . Intervention physicians were trained to deliver PACE exercise counseling protocol s at the index visit , and one reminder telephone call occurred at 1 month . An enhanced intervention group received additional activity reminders . RESULTS At the 6-month follow-up , the control group did not differ significantly from the intervention group for energy expended ( 2,048 kcal/week versus 2,108 kcal/ week , P = 0.77 ) , time spent in walking or other moderate to vigorous activities ( 202 min/week versus 187 min/ week , P = 0.99 ) , mental health , physical function , or behaviors previously shown to predict activity change . Among the intervention patients , the stages-of-change score for Contemplators increased significantly compared with controls ( P = 0.03 ) , but without a significant change in energy expended . Baseline levels of physical activity counseling were high ( 50 % ) , as were baseline patient physical activity levels ( 61 % exercised at least three times a week ) . CONCLUSIONS These results suggest that a one-time PACE counseling session with minimal reinforcement , in a setting with high baseline levels of activity , does not further increase activity . The finding that Contemplators advanced in stage of behavior change suggests that further studies are needed to examine long-term , repeated counseling interventions During the postpartum period , ethnic minority women have higher rates of inactivity/under-activity than white women . The Nā Mikimiki ( “ the active ones ” ) Project is design ed to increase moderate-to-vigorous physical activity over 18 months among multiethnic women with infants 2–12 months old . The study was design ed to test , via a r and omized controlled trial , the effectiveness of a tailored telephone counseling of moderate-to-vigorous physical activity intervention compared to a print/website material s-only condition . Healthy , underactive women ( mean age = 32 ± 5.6 years ) with a baby ( mean age = 5.7 ± 2.8 months ) were enrolled from 2008–2009 ( N = 278 ) . Of the total sample , 84 % were ethnic minority women , predominantly Asian – American and Native Hawaiian . Mean self-reported baseline level of moderate-to-vigorous physical activity was 40 minutes/week with no significant differences by study condition , ethnicity , infant 's age , maternal body mass index , or maternal employment . Women had high scores on perceived benefits , self-efficacy , and environmental support for exercise but low scores on social support for exercise . This multiethnic sample 's demographic and psychosocial characteristics and their perceived barriers to exercise were comparable to previous physical activity studies conducted largely with white postpartum women . The Nā Mikimiki Project 's innovative tailored technology-based intervention and unique population are significant contributions to the literature on moderate-to-vigorous physical activity in postpartum women Purpose . This study examined the broader use of a print-media intervention , which was previously shown to be effective at promoting physical activity to participants recruited from a regional Australian community , as a strategy suitable for a more diverse statewide population sample . Methods . Participants were r and omly selected adults who responded to a telephone interview conducted by the New South Wales Health Department and consented to participate in a r and omized controlled trial . Consenters were allocated to either intervention ( n = 361 ) or control ( n = 358 ) conditions . The intervention , a personalized letter plus stage-targeted booklets , was sent 1 week postbaseline . Data were collected via telephone interview at baseline and 2 and 8 months and were analyzed using repeated measures analysis of variance ( ANOVA ) and χ2 statistics . Results . The groups were similar at baseline ( mean age 43 ± 3 years ; 64 % women ) . Process evaluation showed high intervention recall ( 76 % at 2 months ) and high follow-up response rates ( > 85 % at 8 months ) were achieved . Nonsignificant increases in physical activity were observed ( F 1,719 = 2.18 , p = .14 ) . Discussion . A single mailing of stage-targeted print material s was not effective in promoting increases in physical activity among participants selected from the statewide population . Future research could examine how the effectiveness of print media might be enhanced , possibly by using supplementary media , community-based prompts , or other incentives Purpose . To examine the efficacy of a stage-targeted physical activity intervention among low-income African-Americans . Methods . 207 participants were r and omly assigned to groups and administered baseline measures . Intervention participants were mailed stage-targeted physical activity information , whereas control participants received low-sodium diet brochures . Measures were readministered by phone 1 and 6 months later , with response rates of 69 % and 46 % , respectively . Results . 69 % of participants were African-American and 64 % had a monthly household income of < $ 1000 . A doubly-multivariate analysis of variance indicated that intervention participants reported more physical activity than control participants at 1 month ( F(1 , 204 ) = 4.03 , p < .05 ) . Unlike control participants , intervention participants reported significant stage progression at 1 month , according to a McNemar χ2 test . Gains attenuated by 6 months . Conclusions . The current study supports the use of this intervention among low-income African-Americans . Limitations include use of self-report measures and small sample size Background Attempts to demonstrate the efficacy of interventions aim ed at increasing physical activity ( PA ) have been mixed . Further , studies are seldom design ed in a manner that facilitates the underst and ing of how or why a treatment is effective or ineffective and PA intervention design s should be guided by a heavier reliance upon behavioral theory . The use of a mediating variable framework offers a systematic method ological approach to testing the role of theory , and could also identify the effectiveness of specific intervention components . The primary purpose of this paper was to test the mediating role that cognitive constructs may have played in regards to the positive effect that a workplace behavioral intervention had on leisure-time PA for women . A subsidiary purpose was to examine the cross-sectional relationships of these cognitive constructs with PA behavior . Methods The Physical Activity Workplace Study was a r and omized controlled trial which compared the effects of stage-matched and st and ard print material s upon self-reported leisure-time PA , within a workplace sample at 6 and 12-months . In this secondary analysis we examined the mediation effects of 14 psychosocial constructs across 3 major social-cognitive theories which were operationalized for the intervention material s and measured at baseline , 6 and 12-months . We examined change in PA and change in the psychological constructs employing a mediation strategy proposed by Baron and Kenny for : ( 1 ) the first 6-months ( i.e. , initial change ) , ( 2 ) the second 6-months ( i.e. , delayed change ) , and ( 3 ) the entire 12-months ( overall change ) of the study on 323 women ( n = 213 control/st and ard material s group ; n = 110 stage-matched material s group ) . Results Of the 14 constructs and 42 tests ( including initial , delayed and overall change ) two positive results were identified ( i.e. , overall change in pros , initial change in experiential powerful intervention approaches processes ) , with very small effect sizes . However , these mediating results were eliminated after adjusting for the multiple statistical tests . Conclusions The intervention did not change these mediators in any substantive way , and show a similar pattern to prior research where interventions generally do not result in a change in mediation of behavior change . It is important to report mediation results in r and omized controlled trials whether the findings are null or positive . Future studies may wish to focus on more detailed dose-response issues between mediators and behavior , the inclusion of moderators that could affect individual change , or different mediator constructs at higher levels of measurement specificity . Continued work on innovative and more powerful PA intervention approaches are needed The Flexibility , Toning , and Balance ( FlexToBa ) Trial is a two-armed r and omized controlled trial which will contrast the effects of a DVD-delivered , home-based , physical activity intervention and a Healthy Aging attention control condition on physical activity , functional performance , functional limitations , and quality of life in low active , older adults . This innovative trial will recruit 300 participants across central Illinois who will be r and omized into the intervention arm or control arm of the study . The intervention will last 6 months with a 6 month follow-up . Assessment s at baseline , post intervention and follow-up will include physical activity ( self-report and accelerometry ) , a battery of functional performance measures , functional limitations , quality of life , and an array of psychological health measures . In addition , measures of external validity will be included to determine public health significance of a successful outcome . Participants will engage in a progressive series of activities focusing on flexibility , strengthening , and balance exercises which are demonstrated by a trained exercise leader and age-appropriate models on a series of DVDs . Delivery of the intervention has its basis in social cognitive theory . The specific aims of the trial are ( a ) to determine the effects of the DVD-delivered FlexToBa program on physical activity , functional performance , functional limitations , and quality of life , ( b ) to examine the mediators of the relationships between physical activity and functional limitations and quality of life , ( c ) to assess external validity indicators relative to the intervention , and ( d ) to determine differential effects of the intervention on psychosocial health measures Increasing physical activity is currently considered to be a possible prevention strategy for cancer , obesity , and cardiovascular disease , either alone or in combination with dietary changes . This paper presents results of a r and omized trial of moderate-to-vigorous intensity exercise in middle aged , sedentary women ; specifically , we report changes in and correlates of quality of life and functional status of this exercise intervention program for both the short ( three months ) and longer term ( 12 months ) . The intervention group showed a significant increase in Mental Health score from baseline to 3 months ( p < .01 ) , significantly greater than the change in the control group at 3 months ( p < .01 ) . A similar trend among exercisers was observed for the General Health score ( p < .01 ) , and this finding was significantly greater than the change in control group at 3 months ( p = .01 ) . Change in Social Support – Affection were predictors of the changes in quality of life variables . This study documented improvements in quality of life and general functioning that occurred as a result of participating in an exercise intervention in sedentary middle-aged women Background : Promoting physical activity is an important public health strategy for long-term reductions in incidence or severity of clinical disease . Benefits to health-related quality of life ( HRQL ) and subjective well-being may be as important and take less time to accrue . Purpose : We examined the HRQL benefits of a social-cognitive-theory-based intervention of the Activity Counseling Trial ( ACT ) , both directly in terms of changes in physical fitness and indirectly from increased self-efficacy associated with the intervention . Methods : In ACT , 395 female and 479 male inactive patients ages 35 to 75 years were r and omized to one of : physician advice , advice plus behavioral counseling during primary care visits , or advice plus behavioral counseling that also included telephone contact and behavioral classes . Participants were assessed at baseline , 6 months , and 24 months . HRQL was assessed as perceived quality of life , perceived stress , depression , and general health . Satisfaction with function and appearance , self-efficacy , and social support were also assessed . Results : At 24 months women who received counseling or assistance had significant reductions in daily stress and improvements in satisfaction with body function compared to those receiving advice only . Men had reductions in daily stress across all treatment arms . These results mirrored V02max changes observed per group . Change in barriers self-efficacy was significantly associated with reductions in daily stress at 24 months . Conclusions : Patient benefit from ACT intervention was mediated by enhanced cardiorespiratory fitness and by barriers self-efficacy Background Important health benefits can be derived when low-cost ( e.g. , computer-tailored ) physical activity interventions for older adults demonstrate sustained effects . Purpose The purpose of the study was to conduct in-depth analysis on the long-term efficacy of two tailored physical activity interventions for older adults . Methods A r and omized controlled trial ( n = 1,971 ) with two computer-tailored interventions and a no-intervention control group was conducted . The two tailored interventions consisted of three tailored letters , delivered during 4 months . The basic tailored intervention targeted psychosocial determinants alone , while the environmentally tailored intervention additionally targeted environmental determinants , by providing tailored environmental information . Self-reported behaviors ( i.e. , total physical activity , transport walking and cycling , leisure walking and cycling , and sports ) were measured at baseline and 12 months . Additionally , potential personal , health-related , and psychosocial moderators of the intervention effects were examined . Results The environmentally tailored intervention was effective in changing total physical activity , leisure cycling , and sports compared with the basic intervention and control group . No intervention effects were found for the basic intervention . Moderation analysis revealed that participants with a higher age , lower body mass index , and higher intention were unresponsive to the interventions . Conclusions Providing environmental information is an effective intervention strategy for increasing physical activity behaviors among older adults , especially among certain “ at-risk ” subgroups such as lower educated , overweight , or insufficiently active participants . Moderation analysis was perceived as a promising method for identifying meaningful subgroups that are unaffected by an intervention , which should receive special attention in future interventions Sedentary behavior among older adults increases risk for chronic diseases . Physicians in a primary care setting can play an important role in promoting physical activity adoption among their older patients . The Physically Active for Life ( PAL ) project was a r and omized , controlled trial comparing the efficacy of brief physician-delivered physical activity counseling to usual care on self-reported physical activity levels . The physical activity counseling was based on the Transtheoretical Model of Change and social learning theory . Twenty-four community-based primary care medical practice s were recruited into the study ; 12 were r and omized to the Intervention condition and 12 to the Control condition . Physicians in the Intervention practice s received training in the delivery of brief physical activity counseling . Subjects in the Intervention practice s ( n=181 ) received brief activity counseling matched to their stage of motivational readiness for physical activity , a patient manual , a follow-up appointment with their physician to discuss activity counseling , and newsletter mailings . Subjects in the Control practice s ( n=174 ) received st and ard care . Measures of motivational readiness for physical activity and the Physical Activity Scale for the Elderly ( PASE ) were administered to subjects in both conditions at baseline , 6 weeks following their initial appointment , and at 8 months . Results showed that at the 6-week follow-up , subjects in the Intervention condition were more likely to be in more advanced stages of motivational readiness for physical activity than subjects in the Control condition . This effect was not maintained at the 8 month follow-up and the intervention did not produce significant changes in PASE scores . Results suggest that more intensive , sustained interventions may be necessary to promote the adoption of physical activity among sedentary , middle-aged , and older adults in primary care medical practice Background : Ethnic minorities or those with low socioeconomic status ( SES ) are at increased risk of cardiovascular disease , type 2 diabetes , and all-cause mortality , compared to higher SES Whites . National surveys also indicate that low-income , ethnic minority women have the highest rates of inactivity in the United States . Purpose : This study ( the Increasing Motivation for Physical ACTivity or IMPACT study ) promoted adoption and maintenance of physical activity ( PA ) in sedentary , low-income women participating in federally funded job training programs . Methods : The study consisted of 2 months of weekly 1-hr classes , then r and om assignment to 10 months of either home-based telephone counseling for PA plus information and feedback via mailed newsletters ( Phone + Mail Counseling condition ) or just the mailed newsletters ( Mail Support condition ) . The IMPACT intervention included behavior change strategies for PA as well as discussion s related to motivational readiness for PA change . Participants completed surveys and physiological assessment s at baseline after the classes ended ( i.e. , at 10 weeks ) and at 6 and 12 months postbaseline . Seventy-three percent of r and omized participants ( n = 72 ) were Latina , with a mean age of 32 ± 10 years . More than half the women had not completed high school , and 73 % had an annual income less than $ 20,000 . Results : After 10 months of a homebased intervention , women in the phone + mail counseling condition had significantly greater increases in estimated total energy expenditure compared to women in the mail support condition ( p < .05 ) . Conclusions : Regular PA counseling delivered via the telephone and through the mail appears effective for encouraging regular PA among low-income women transitioning from welfare or job training to the workforce Background : Intervention trials with self-selected participants have shown that mailed stage-targeted print material s can increase participation in physical activity in the short term . We examined the effects of a mailed stage-targeted print intervention design ed to promote physical activity , in a r and om sample of adults living in a regional city . Method : Participants ( n = 462 , 40–60 years of age ) were r and omly allocated to an intervention in - 227 ) or control group ( n - 235 ) . Measures included vali date d 2-week physical activity recall and stage of motivational readiness for physical activity . The intervention consisted of a single mailing of a letter and full-color stage-targeted booklets ( specific to precontemplation , contemplation , preparation , and action/maintenance ) 1 week postbaseline . Follow-up interviews were conducted at 2 and 6 months postbaseline . Results : After 2 months , participants in the intervention group were significantly More likely to meet the current American College of Sports Medicine/Centers for Disease Control and Prevention recommendation for sufficient physical activity than those in the control group ( adjusted odds ratio [ OR ] - 2.40 ; 95 % confidence interval [ CI ] = 1.44–3.99 ) . After 6 months , intervention participants who reported receiving and reading the intervention material s were significantly more likely to be meeting the sufficient physical activity criterion compared with the control group ( adjusted OR = 2.03 ; 95 % Cl = 1.16–3.56 ) . Conclusions : The stage-targeted print intervention was effective in promoting short-term increases in physical activity and was most effective for participants who recognized and used the material s. This low-cost , generalizable intervention has demonstrated potential as a practical population -based physical activity promotion strategy . Further research is required before widespread dissemination would be justified , as additional strategies may be required to ensure sustained change Background Effective interventions are needed to reduce the chronic disease epidemic . The Internet has the potential to provide large population s with individual advice at relatively low cost . Objective The focus of the study was the Web-based tailored physical activity intervention Active-online . The main research questions were ( 1 ) How effective is Active-online , compared to a nontailored website , in increasing self-reported and objective ly measured physical activity levels in the general population when delivered in a real-life setting ? ( 2 ) Do respondents recruited for the r and omized study differ from spontaneous users of Active-online , and how does effectiveness differ between these groups ? ( 3 ) What is the impact of frequency and duration of use of Active-online on changes in physical activity behavior ? Methods Volunteers recruited via different media channels completed a Web-based baseline survey and were r and omized to Active-online ( intervention group ) or a nontailored website ( control group ) . In addition , spontaneous users were recruited directly from the Active-online website . In a subgroup of participants , physical activity was measured objective ly using accelerometers . Follow-up assessment s took place 6 weeks ( FU1 ) , 6 months ( FU2 ) , and 13 months ( FU3 ) after baseline . Results A total of 1531 respondents completed the baseline question naire ( intervention group n = 681 , control group n = 688 , spontaneous users n = 162 ) ; 133 individuals had valid accelerometer data at baseline . Mean age of the total sample was 43.7 years , and 1146 ( 74.9 % ) were women . Mixed linear models ( adjusted for sex , age , BMI category , and stage of change ) showed a significant increase in self-reported mean minutes spent in moderate- and vigorous-intensity activity from baseline to FU1 ( coefficient = 0.14 , P = .001 ) and to FU3 ( coefficient = 0.19 , P < .001 ) in all participants with no significant differences between groups . A significant increase in the proportion of individuals meeting the HEPA recommendations ( self-reported ) was observed in all participants between baseline and FU3 ( OR = 1.47 , P = .03 ) , with a higher increase in spontaneous users compared to the r and omized groups ( interaction between FU3 and spontaneous users , OR = 2.95 , P = .02 ) . There were no increases in physical activity over time in any group for objective ly measured physical activity . A significant relation was found between time spent on the tailored intervention and changes in self-reported physical activity between baseline and FU3 ( coefficient = 1.13 , P = .03 , intervention group and spontaneous users combined ) . However , this association was no longer significant when adjusting for stage of change . Conclusions In a real-life setting , Active-online was not more effective than a nontailored website in increasing physical activity levels in volunteers from the general population . Further research may investigate ways of integrating Web-based physical activity interventions in a wider context , for example , primary care or workplace health promotion Background The aim of this study was to explore the working mechanisms of a computer tailored physical activity intervention for older adults with environmental information compared to a basic tailored intervention without environmental information . Method A clustered r and omized controlled trial with two computer tailored interventions and a no-intervention control group was conducted among 1971 adults aged ≥ 50 . The two tailored interventions were developed using Intervention Mapping and consisted of three tailored letters delivered over a four-month period . The basic tailored intervention targeted psychosocial determinants alone , while the environmentally tailored intervention additionally targeted environmental determinants , by providing tailored environmental information . Study outcomes were collected with question naires at baseline , three and six months and comprised total physical activity ( days/week ) , walking ( min/week ) , cycling ( min/week ) , sports ( min/week ) , environmental perceptions and use and appreciation of the interventions . Results Mediation analyses showed that changes in cycling , sports and total physical activity behaviour induced by the environmentally tailored intervention were mediated by changes in environmental perceptions . Changes in environmental perceptions did not mediate the effect of the basic tailored intervention on behaviour . Compared with the basic tailored intervention , the environmentally tailored intervention significantly improved cycling behaviour ( τ = 30.2 ) . Additionally , the tailored letters of the environmentally tailored intervention were better appreciated and used , although these differences did not mediate the intervention effect . Discussion This study gave some first indications of the relevance of environmental perceptions as a determinant of changing physical activity behaviours and the potential effectiveness of providing environmental information as an intervention strategy aim ed at enhancing physical activity behaviour among older adults Background It is well recognised that the adoption and longer term adherence to physical activity by adults to reduce the risk of chronic disease is a challenge . Interventions , such as group and home based physical activity programs , have been widely reported upon . However few studies have directly compared these interventions over the longer term to determine their adherence and effectiveness . Participant preference for home based or group interventions is important . Some evidence suggests that home based physical activity programs are preferred by middle aged adults and provide better long term physical activity adherence . Physiotherapists may also be useful in increasing physical activity adherence , with limited research on their impact . Methods ' Physical Activity at Home ' is a 2 year pragmatic r and omised control trial , with a non-r and omised comparison to group exercise . Middle-aged adults not interested in , or unable to attend , a group exercise program will be targeted . Sedentary community dwelling 50 - 65 year olds with no serious medical conditions or functional impairments will be recruited via two mail outs using the Australian federal electoral roll . The first mail out will invite participants to a 6 month community group exercise program . The second mail out will be sent to those not interested in the group exercise program inviting them to take part in a home based intervention . Eligible home based participants will be r and omised into a 6 month physiotherapy-led home based physical activity program or usual care . Outcome measures will be taken at baseline , 6 , 12 , 18 and 24 months . The primary outcome is physical activity adherence via exercise diaries . Secondary outcomes include the Active Australia Survey , accelerometry , aerobic capacity ( step test ) , quality of life ( SF-12v2 ) , blood pressure , waist circumference , waist-to-hip ratio and body mass index . Costs will be recorded prospect ively and qualitative data will be collected . Discussion The planned 18 month follow-up post intervention will provide an indication of the effectiveness of the group and home based interventions in terms of adherence to physical activity , health benefits and cost . If the physiotherapy-led home based physical activity program is successful it could provide an alternative option for physical activity program delivery across a number of setting s . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : Two studies were undertaken to compare strategies for the adoption and maintenance of moderate-intensity , home-based exercise training . In the study of adoption , 52 men and women who had served for 6 months as controls for a study of moderate-intensity , home-based exercise training received 30 minutes of baseline instruction . They were then r and omized to receive continuing instruction and support through 10 staff-initiated telephone contacts of 5 minutes each every 2 weeks , or to receive no telephone contacts . In subjects receiving telephone contacts , peak oxygen uptake increased significantly after 6 months , whereas no increase was observed in subjects receiving no staff support ( p less than 0.05 ) . In the maintenance study , 51 men and women who had significantly increased their peak oxygen uptake by 6 months of moderate-intensity , home-based exercise training were r and omized to undergo daily self-monitoring and receive adherence instructions , or undergo weekly self-monitoring only , during a second 6-month period of training . Subjects performing daily self-monitoring reported completing significantly more exercise training sessions during the 6 months of training than subjects performing weekly self-monitoring ; functional capacity in both groups remained higher than before training ( p less than 0.05 ) . Taken together , these studies suggest that brief baseline instruction followed by continuing telephone contact with staff can be used to help people adopt a moderate-intensity , home-based exercise training program that can be maintained by simple self-monitoring strategies Background Increased physical activity levels benefit both an individuals ' health and productivity at work . The purpose of the current study was to explore the impact and cost-effectiveness of a workplace physical activity intervention design ed to increase physical activity levels . Methods A total of 1260 participants from 44 UK worksites ( based within 5 organizations ) were recruited to a cluster r and omized controlled trial with worksites r and omly allocated to an intervention or control condition . Measurement of physical activity and other variables occurred at baseline , and at 0 months , 3 months and 9 months post-intervention . Health outcomes were measured during a 30 minute health check conducted in worksites at baseline and 9 months post intervention . The intervention consisted of a 3 month tool-kit of activities targeting components of the Theory of Planned Behavior , delivered in-house by nominated facilitators . Self-reported physical activity ( measured using the IPAQ short-form ) and health outcomes were assessed . Results and discussion Multilevel modelling found no significant effect of the intervention on MET minutes of activity ( from the IPAQ ) at any of the follow-up time points controlling for baseline activity . However , the intervention did significantly reduce systolic blood pressure ( B = -1.79 mm/Hg ) and resting heart rate ( B = -2.08 beats ) and significantly increased body mass index ( B = .18 units ) compared to control . The intervention was found not to be cost-effective , however the substantial variability round this estimate suggested that further research is warranted . Conclusions The current study found mixed support for this worksite physical activity intervention . The paper discusses some of the tensions involved in conducting rigorous evaluations of large-scale r and omized controlled trials in real-world setting s . Trial registration Current controlled trials IS RCT CONTEXT Physical activity is important for health , yet few studies have examined the effectiveness of physical activity patient counseling in primary care . OBJECTIVE To compare the effects of 2 physical activity counseling interventions with current recommended care and with each other in a primary care setting . DESIGN The Activity Counseling Trial , a r and omized controlled trial with recruitment in 1995 - 1997 , with 24 months of follow-up . SETTING Eleven primary care facilities affiliated with 3 US clinical research centers . PARTICIPANTS Volunteer sample of 395 female and 479 male inactive primary care patients aged 35 to 75 years without clinical cardiovascular disease . INTERVENTIONS Participants were r and omly assigned to 1 of 3 groups : advice ( n = 292 ) , which included physician advice and written educational material s ( recommended care ) ; assistance ( n = 293 ) , which included all the components received by the advice group plus interactive mail and behavioral counseling at physician visits ; or counseling ( n = 289 ) , which included the assistance and advice group components plus regular telephone counseling and behavioral classes . MAIN OUTCOME MEASURES Cardiorespiratory fitness , measured by maximal oxygen uptake ( VO(2)max ) , and self-reported total physical activity , measured by a 7-day Physical Activity Recall , compared among the 3 groups and analyzed separately for men and women at 24 months . RESULTS At 24 months , 91.4 % of the sample had completed physical activity and 77.6 % had completed cardiorespiratory fitness measurements . For women at 24 months , VO(2)max was significantly higher in the assistance group than in the advice group ( mean difference , 80.7 mL/min ; 99.2 % confidence interval [ CI ] , 8.1 - 153.2 mL/min ) and in the counseling group than in the advice group ( mean difference , 73.9 mL/min ; 99.2 % CI , 0.9 - 147.0 mL/min ) , with no difference between the counseling and assistance groups and no significant differences in reported total physical activity . For men , there were no significant between-group differences in cardiorespiratory fitness or total physical activity . CONCLUSIONS Two patient counseling interventions differing in type and number of contacts were equally effective in women in improving cardiorespiratory fitness over 2 years compared with recommended care . In men , neither of the 2 counseling interventions was more effective than recommended care OBJECTIVE To evaluate the cost-effectiveness of non-face-to-face interventions for increasing physical activity in sedentary adults . The study took place in Providence , Rhode Isl and between the years 2000 and 2004 . METHODS Two hundred and thirty-nine participants were r and omized to Phone , Print or a contact control . Phone and Print groups were mailed regular surveys regarding their level of physical activity , motivational readiness and self-efficacy . Surveys were scanned by a computer expert system to generate feedback reports . Phone group participants received feedback by telephone . Print group participants received feedback by mail . The contact control group received mailings unrelated to physical activity . Intervention costs were assessed prospect ively , from a payer perspective . Physical activity was measured using the 7-day Physical Activity Recall . Ambulatory health service use was assessed via monthly surveys . RESULTS The Print intervention was more economically efficient than the Phone intervention in engaging participants in a more active lifestyle . CONCLUSION The Print intervention provides an efficient approach to increasing physical activity . Research is needed to determine the cost-effectiveness of the intervention in a more diverse population , within the context of the health service delivery system and over a longer period of time Background Systematic review s have identified a range of brief interventions which increase physical activity in previously sedentary people . There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity . This study assesses whether it is worth providing motivational interviews , three months after giving initial advice , to those who have become more active . Methods / Design Study c and i date s ( n = 1500 ) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD . Only those that have increased their physical activity after three months ( n = 600 ) will be r and omised into the study . These participants will receive either a " mini booster " ( n = 200 ) , " full booster " ( n = 200 ) or no booster ( n = 200 ) . The " mini booster " consists of two telephone calls one month apart to discuss physical activity and maintenance strategies . The " full booster " consists of a face-to-face meeting with the facilitator at the same intervals . The purpose of these booster sessions is to help the individual maintain their increase in physical activity . Differences in physical activity , quality of life and costs associated with the booster interventions , will be measured three and nine months from r and omisation . The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield , which have large , ethnically diverse population s , high levels of economic deprivation , low levels of physical activity , poorer health and shorter life expectancy . Participants will be recruited through general practice s and community groups , as well as by postal invitation , to ensure the participation of minority ethnic groups and those with lower levels of literacy . Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities . A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10 % sample . Discussion The choice of study population , study interventions , brief intervention preceding the study , and outcome measure are discussed . Trial Registration Current Controlled Trials : IS RCT N56495859 ; Clinical Trials.gov : NCT00836459 BACKGROUND Sedentary lifestyle is associated with adverse health outcomes . Available evidence suggests that , despite positive attitudes toward regular exercise in promoting a healthy lifestyle , few physicians actually prescribe exercise for their patients . Barriers include lack of skills and st and ard office instruments . Because primary care physicians have regular contact with a large proportion of the population , the impact of preventive health interventions may be great . OBJECTIVES To determine the effect of an exercise prescription instrument ( i.e. , Step Test Exercise Prescription [ STEP ] ) , compared to usual-care exercise counseling delivered by primary care doctors on fitness and exercise self-efficacy among elderly community-dwelling patients . DESIGN R and omized controlled trial ; baseline assessment and intervention delivery with postintervention follow-up at 3 , 6 , and 12 months . SETTING Four large ( > 5000 active patient files ) academic , primary care practice s : three in urban setting s and one in a rural setting , each with four primary care physicians ; two clinics provided the STEP intervention and two provided usual care control . PARTICIPANTS A total of 284 healthy community-dwelling patients ( 72 per clinic ) aged > 65 years were recruited in 1998 - 1999 . INTERVENTION STEP included exercise counseling and prescription of an exercise training heart rate . MAIN OUTCOME MEASURES The primary outcome measure was aerobic fitness ( VO(2max ) ) . Secondary outcomes included predicted VO(2max ) from the STEP test , exercise self-efficacy ( ESE ) , and clinical anthropometric parameters . RESULTS A total of 241 subjects ( 131 intervention , 110 control ) completed the trial . VO(2max ) was significantly increased in the STEP intervention group ( 11 % ; 21.3 to 24ml/kg/min ) compared to the control group ( 4 % ; 22 to 23ml/kg/min ) over 6 months ( p < 0.001 ) , and 14 % ( 21.3 to 24.9ml/kg/min ) and 3 % ( 22.1 to 22.8ml/kg/min ) , respectively , at 12 months ( p < 0.001 ) . A similar significant increase in ESE ( 32 % ; 4.6 vs 6.8 ) was observed for the STEP group compared to the control group ( 22 % ; 4.2 vs 5.4 ) at 12 months ( p < 0.001 ) . Systolic blood pressure decreased 7.3 % and body mass index decreased 7.4 % in the STEP group , with no significant change in the control group ( p < 0.05 ) . Exercise counseling time was significantly ( p < 0.02 ) longer in the STEP ( 11.7+/-3.0 min ) compared to the control group ( 7.1+/-7.0 min ) , but more ( p < 0.05 ) subjects completed > or = 80 % of available exercise opportunities in the STEP group . CONCLUSIONS Primary care physicians can improve fitness and exercise confidence of their elderly patients using a tailored exercise prescription ( e.g. , STEP ) . Further , STEP appears to maintain benefits to 12 months and may improve exercise adherence . Future study should determine the impact of combining cognitive/behavior change strategies with STEP Background While there are increasing data implicating poor recognition of physical inactivity as a potential barrier to healthy behaviour change , the efficacy of feedback to promote physical activity is uncertain . Using a r and omised controlled trial nested within a population -based cohort study , we plan to test three variations of physical activity feedback against a control group . Our primary objective is to assess the efficacy of physical activity feedback in promoting physical activity behaviour change . Secondary objectives are to determine the influence of feedback on physical activity awareness and cognitions , and to compare behavioural effects by type of feedback . Methods / Design We aim to recruit 500 healthy participants aged 30 to 55 years from the ongoing Fenl and Study ( Cambridge , UK ) . Following careful phenotyping during baseline measurement ( anthropometric , clinical , body composition and fitness measurements , as well as question naires assessing self-reported and self-rated physical activity , psychosocial correlates of physical activity behaviour , diet , lifestyle and general health ) , participants wear a combined heart rate and movement sensor ( Actiheart ® ) for six continuous days and nights . After receipt of the physical activity data ( around 2 weeks later ) , participants are r and omly allocated to either a control group ( no feedback ) or one of three types of personalised physical activity feedback ( ' simple ' , ' visualised ' or ' context ualised ' ) , and complete repeat measures of self-rated physical activity and psychosocial correlates . Approximately five weeks after receiving feedback , all participants wear the Actiheart ® for another six-day follow-up period and complete repeat question naires . Values at outcome , adjusted for baseline , will be compared between r and omised groups . Discussion Given the r and omised trial design and use of objective measure of physical activity , this study is likely to provide valuable insights into the efficacy of a feedback intervention in changing physical activity behaviour , as well as the psychological mechanisms involved . Trial Registration Current Controlled Trials : IS RCT Background Epidemiological evidence suggests that decrease in sedentary behaviour is beneficial for health . This family based r and omized controlled trial examines whether face-to-face delivered counselling is effective in reducing sedentary time and improving health in adults and increasing moderate-to-vigorous activities in children . Methods The families are r and omized after balancing socioeconomic and environmental factors in the Jyväskylä region , Finl and . Inclusion criteria are : healthy men and women with children 3 - 8 years old , and having an occupation where they self-reportedly sit more than 50 % of their work time and children in all-day day-care in kindergarten or in the first grade in primary school . Exclusion criteria are : body mass index > 35 kg/m2 , self-reported chronic , long-term diseases , families with pregnant mother at baseline and children with disorders delaying motor development . From both adults and children accelerometer data is collected five times a year in one week periods . In addition , fasting blood sample s for whole blood count and serum metabonomics , and diurnal heart rate variability for 3 days are assessed at baseline , 3 , 6 , 9 , and 12 months follow-up from adults . Quadriceps and hamstring muscle activities providing detailed information on muscle inactivity will be used to realize the maximum potential effect of the intervention . Fundamental motor skills from children and body composition from adults will be measured at baseline , and at 6 and 12 months follow-up . Question naires of family-influence-model , health and physical activity , and dietary records are assessed . After the baseline measurements the intervention group will receive tailored counselling targeted to decrease sitting time by focusing on commute and work time . The counselling regarding leisure time is especially targeted to encourage toward family physical activities such as visiting playgrounds and non-built environments , where children can get diversified stimulation for play and practice fundamental of motor skills . The counselling will be reinforced during the first 6 months followed by a 6-month maintenance period . Discussion If shown to be effective , this unique family based intervention to improve lifestyle behaviours in both adults and children can provide translational model for community use . This study can also provide knowledge whether the lifestyle changes are transformed into relevant biomarkers and self-reported health . Trial registration numberIS RCT N : IS RCT OBJECTIVE To examine putative mediators of a 12-month motivationally tailored physical activity ( PA ) promotion intervention . DESIGN We r and omly assigned 239 healthy , underactive adults ( moderate-vigorous physical activity < 90 min/week ; mean age = 47.5 years ; 82 % women ) to receive ( a ) print-based feedback , ( b ) phone-based feedback , or ( c ) contact control . PRIMARY OUTCOME PA at baseline , 6 , and 12 months , as measured by the 7-day physical activity recall interview . MEDIATORS : Four TransTheoretical Model constructs explicitly targeted by the intervention ( i.e. , self-efficacy , decisional balance , cognitive and behavioral processes of change ) , as well as four additional constructs linked to PA behavior change ( i.e. , social support , outcome expectancy , PA enjoyment , exercise-induced feelings ) . RESULTS Multivariate mediation analyses were used to analyze longitudinal PA outcomes . Changes in behavioral processes and one aspect of exercise-induced feelings ( revitalization ) satisfied both action theory ( i.e. , treatment effects on mediators ) and conceptual theory ( i.e. , mediator effects on PA ) tests at 6 and 12 months and emerged as statistically significant mediators of treatment effects on PA across delivery channels ( ps < .014 ) . Cognitive processes , self-efficacy , decisional balance , and social support for PA participation satisfied Action Theory tests at both 6 and 12 months , but failed conceptual theory tests . Delayed intervention effects were observed on other aspects of exercise-induced feelings , PA enjoyment , and outcome expectancies , but these variables failed mediation testing at 12 months . CONCLUSION Findings are consistent with previous research illustrating the importance of behavioral processes of change , but also indicate that affective response to PA may warrant more attention as a potential target of behavior change programs The aim of this study was to evaluate the effectiveness of a computer-tailored physical activity intervention delivered through the Internet in a real-life setting . Healthy adults ( n=526 ) , recruited in six worksites , between 25 and 55 years of age were r and omized to one of three conditions receiving , respectively , ( i ) online-tailored physical activity advice + stage-based reinforcement e-mails , ( ii ) online-tailored physical activity advice only , ( iii ) online non-tailored st and ard physical activity advice . At 6-month follow-up , no differences in physical activity between study conditions were found ; total physical activity , physical activity at moderate intensity and physical activity in leisure time significantly increased in all study conditions between baseline and follow-up . Further evaluation of the intervention material s showed that the tailored advice was more read , printed and discussed with others than the st and ard advice . Most of the respondents in the e-mail group indicated to be satisfied about the number , frequency and usefulness of the stage-based e-mails . In conclusion , although tailored advice was appreciated more than st and ard advice , no evidence was found that an online-tailored physical activity intervention program outperformed online st and ard information Background Physical inactivity is an independent risk factor for diabetes and heart disease . There is evidence that increasing physical activity can reduce the risk of developing these chronic diseases , but less evidence about effective ways to increase adherence to physical activity . Interventions are therefore needed that produce sustained increases in adherence to physical activity , are cost-effective and improve clinical endpoints . Methods The Women 's Lifestyle Study is a two year r and omized controlled trial involving a nurse-led intervention to increase physical activity in 40–74 year old physically inactive women recruited from primary care . Baseline measures were assessed in a face-to-face interview with a primary care nurse . The intervention involved delivery of a ' Lifestyle script ' by a primary care nurse followed by telephone counselling for nine months and a face-to-face nurse visit at six months . Outcome measurements are assessed at 12 and 24 months . The primary outcome is physical activity measured using a vali date d physical activity question naire . Secondary outcomes include blood pressure , weight , waist circumference , physical fitness ( step test ) , serum HbA1c , fasting glucose , lipids , insulin , and quality of life ( SF36 ) . Costs were measured prospect ively to allow a subsequent cost-effectiveness evaluation if the trial is positive . Discussion Due to report in 2008 , the Women 's Lifestyle Study tests the effectiveness of an enhanced low-cost , evidence -based intervention in increasing physical activity , and improving cardiovascular and diabetes risk indicators over two years . If successful in demonstrating improvements in health outcomes , this r and omized controlled trial will be the first to demonstrate long-term cardiovascular and diabetes risk health benefit , in addition to improvements in physical activity , from a sustainable physical activity intervention based in primary care . Trial Registration Australian Clinical Trials Registry ( ACTR ) , ACTRN012605000490673 Background In many countries exercise prescriptions are used in an attempt to initiate a physically active lifestyle in sedentary population s. Previous studies have primarily evaluated low intensive exercise prescription interventions and found moderately positive effects on physical activity and aerobic fitness . In a highly intensive Danish exercise prescription scheme called ' Exercise on Prescription ' ( EoP ) the general practitioners can prescribe EoP to sedentary patients with lifestyle diseases . The aim of this r and omized trial is to assess the short- and long-term effects of the EoP scheme . Thus , the aim of this paper is to describe the r and omized controlled trial design ed for evaluating effectiveness of EoP , and to present results from validations of outcome measures . Methods / Design EoP involves a 16-week supervised training intervention and five counselling sessions ( health profiles ) . All patients referred to EoP were eligible for the trial and were offered participation during the baseline health profile . Comparisons between the EoP group and the control group were made at baseline , and after four and ten months . Physiological measures used were maximal oxygen uptake ( VO2max ) , glycosylated haemoglobin ( HbA1c ) , bodyweight , and BMI . Patient-reported measures used were physical activity , health-related quality of life , amount and intensity of exercise , compliance with national guidelines for physical activity , and physical fitness . The validation of the cycle ergometer test found a strong correlation between maximal work capacity and VO2max , and acceptable test-retest reliability at group level . Calibration of the HbA1c apparatus was stable over ten weeks with minimal use , and test-retest reliability was good . High agreement percents were found for test-retest reliability for the self-administered question naire . Discussion The trial is design ed to provide information about the effectiveness of the EoP scheme . The trial is part of a health technology assessment of EoP , which besides the effectiveness covers the patient perspective , the organization , and the health economy . All three methods vali date d were found useful for the EoP trial PURPOSE Given the prevalence of physical inactivity among American adults , convenient , low-cost interventions are strongly indicated . This study determined the 6- and 12-month effectiveness of telephone interventions delivered by health educators or by an automated computer system in promoting physical activity . DESIGN Initially inactive men and women age 55 years and older ( N = 218 ) in stable health participated . Participants were r and omly assigned to human advice , automated advice , or health education control . MEASURES The vali date d 7-day physical activity recall interview was used to estimate minutes of moderate to vigorous physical activity . Physical activity differences by experimental arm were verified on a r and om sub sample via accelerometry . RESULTS Using intention-to-treat analysis , at 6 months , participants in both interventions , although not differing from one another , showed significant improvements in weekly physical activity compared with controls . These differences were generally maintained at 12 months , with both intervention arms remaining above the target of 150 min per week of moderate to vigorous physical activity on average . CONCLUSION Automated telephone-linked delivery systems represent an effective alternative for delivering physical activity advice to inactive older adults There is growing interest in promoting health for people with disabilities , yet evidence regarding community-based interventions is sparse . This paper describes the design details of a r and omized controlled trial ( RCT ) that will test the effectiveness of a multi-component behaviorally based , intervention to promote exercise adoption ( over 6 months ) and maintenance ( up to one year ) among wheelchair users and includes descriptive data on participant characteristics at baseline . Participants were r and omly assigned to either a staff-supported intervention group or a self-guided comparison group . The primary study aim is to assess the effectiveness of the multi-component behaviorally based intervention for promoting physical activity adoption and maintenance . The RCT will also assess the physical and psychosocial effects of the intervention and the complex interplay of factors that influence the effectiveness of the intervention . Therefore , the primary outcome derives from participant reports of weekly exercise ( type , frequency , duration ) over 52 weeks . Secondary outcomes collected on four occasions ( baseline , 3 months , 6 months , 12 months ) included physiological outcomes ( VO(2 ) peak , strength ) , disability-related outcomes ( pain , fatigue , participation ) , and psychosocial outcomes ( exercise self-efficacy , exercise barriers , quality of life , depression , mood ) . This study will provide evidence regarding the effectiveness of a multi-component behaviorally based intervention for promoting exercise adoption among people with mobility impairments that necessitate wheelchair use BACKGROUND Little is known about factors affecting adherence to highly-structured and supervised exercise programs in older people . METHODS Healthy , inactive older ( ≥65 y ) women ( N = 30 ) were r and omized into a 1 ) higher- ( ATH-80 % VO₂peak ) ; 2 ) moderate- ( ATM-65 % VO₂peak ) intensity aerobic ; or 3 ) lower-intensity resistance ( RTL ; 50 % VO₂peak ) group . All 3 groups exercised 4 days·week⁻¹ for an average of 45 to 70 min·session⁻¹ over 9 months . Adherence ( % ) was defined as the proportion of prescribed sessions ( N = 144 ) in which subjects achieved their 1 ) prescribed heart rate ( intensity adherence ) and 2 ) their prescribed duration ( duration adherence ) . Primary determinants of adherence included prescribed intensity ( METs ) and prescribed duration ( min ) , as well as age , body composition , VO₂peak , and exercise self-efficacy score . RESULTS Intensity adherence was nearly 100 % for all 3 groups , while duration adherence was 95 % , 91 % , and 85 % in the RTL , ATH , and ATM groups , respectively . Prescribed exercise duration was the strongest determinant of duration adherence ( r = -0.72 ; P < .0001 ) , independent of prescribed METs , age , VO₂peak , and body composition . CONCLUSIONS Due to competing lifestyle dem and s , exercise intensity may be less of a factor in adherence among older women than is exercise duration Study objective : To compare health walks , a community based lay-led walking scheme versus advice only on physical activity and cardiovascular health status in middle aged adults . Design : R and omised controlled trial with one year follow up . Physical activity was measured by question naire . Other measures included attitudes to exercise , body mass index , cholesterol , aerobic capacity , and blood pressure . Setting : Primary care and community . Participants : 260 men and women aged 40–70 years , taking less than 120 minutes of moderate intensity activity per week . Main results : Seventy three per cent of people completed the trial . Of these , the proportion increasing their activity above 120 minutes of moderate intensity activity per week was 22.6 % in the advice only and 35.7 % in the health walks group at 12 months ( between group difference = 13 % ( 95 % CI 0.003 % to 25.9 % ) p=0.05 ) . Intention to treat analysis , using the last known value for missing cases , demonstrated smaller differences between the groups ( between group difference = 6 % ( 95 % CI −5 % to 16.4 % ) ) with the trend in favour of health walks . There were improvements in the total time spent and number of occasions of moderate intensity activity , and aerobic capacity , but no statistically significant differences between the groups . Other cardiovascular risk factors remained unchanged . Conclusions : There were no significant between group differences in self reported physical activity at 12 month follow up when the analysis was by intention to treat . In people who completed the trial , health walks was more effective than giving advice only in increasing moderate intensity activity above 120 minutes per week OBJECTIVE To evaluate three strategies for promoting physical activity ( PA ) in a primary care setting . METHOD Data were collected between 2002 and 2004 from 136 patients attending two general practice s in Brisbane , Australia . Inactive patients ( 50 - 70 years ) were r and omly allocated to one of three hierarchical intervention groups : the general practitioner ( GP ) group received ' brief ' advice ; the GP+ES group also received behavior change advice from an exercise scientist ( ES ) ; and the GP+ES+P group also received a pedometer . Self-reported PA and its determinants were measured at baseline and weeks 12 and 24 . Cardio-respiratory variables were measured at baseline and week 12 . RESULTS Overall , mean PA time increased by 84 and 128 min/week at weeks 12 and 24 ( p<.01 ) with no significant group differences . Small improvements in blood pressure and post-exercise heart rate were observed . At week 24 , the GP+ES+P group were more likely to report meeting PA guidelines than the GP group ( OR=2.39 95 % CI : 1.01 , 5.64 ) . CONCLUSION PA levels can be increased in mid- to older-age adults , either by brief advice from motivated GPs alone , or from collaboration between GPs and ESs . The most intense intervention ( GP+ES+P ) showed the most promising results BACKGROUND Ethnic minorities and lower-income adults have among the highest rates of obesity and lowest levels of regular physical activity ( PA ) . The Positive Action for Today 's Health ( PATH ) trial compares three communities that are r and omly assigned to different levels of an environmental intervention to improve safety and access for walking in low income communities . DESIGN AND SETTING Three communities matched on census tract information ( crime , PA , ethnic minorities , and income ) were r and omized to receive either : an intervention that combines a police-patrolled-walking program with social marketing strategies to promote PA , a police-patrolled-walking only intervention , or no-walking intervention ( general health education only ) . Measures include PA ( 7-day accelerometer estimates ) , body composition , blood pressure , psychosocial measures , and perceptions of safety and access for PA at baseline , 6 , 12 , 18 , and 24 months . INTERVENTION The police-patrolled walking plus social marketing intervention targets increasing safety ( training community leaders as walking captains , hiring off-duty police officers to patrol the walking trail , and containing stray dogs ) , increasing access for PA ( marking a walking route ) , and utilizes a social marketing campaign that targets psychosocial and environmental mediators for increasing PA . MAIN HYPOTHESES/ OUTCOMES : It is hypothesized that the police-patrolled walking plus social marketing intervention will result in greater increases in moderate-to-vigorous PA as compared to the police-patrolled-walking only or the general health intervention after 12 months and that this effect will be maintained at 18 and 24 months . CONCLUSIONS Implication s of this community-based trial are discussed PURPOSE Aging , in conjunction with decreasing physical activity , is associated with a range of health problems . Simple , low-maintenance , population -based means of promoting activity to counteract the age-associated decline are required . We therefore assessed the effect of pedometry and buddy support to increase physical activity . METHODS We undertook a clustered r and omized trial ( HKCTR-346 ) of 24 community centers involving 399 older Chinese participants ( ≥ 60 yr ) . Centers were r and omly allocated to 1 ) pedometry and buddy , 2 ) pedometry and no buddy , 3 ) no pedometry and buddy , and 4 ) no pedometry and no buddy with a 2 × 2 factorial design . The trial simultaneously tested the individual and combined effects of the interventions . The intervention groups also received monthly organized group activities to provide encouragement and support . Outcome measures were assessed at 6 and 12 months , including physical fitness and activity and cardiovascular disease risk factors ( anthropometry and blood pressure ) . RESULTS From the 24 centers , 356 volunteers ( 89.2 % ) completed the study . Those receiving the interventions had higher mean physical activity levels at 12 months of 1820 ( 95 % confidence interval ( CI ) = 1360 - 2290 ) and 1260 ( 95 % CI = 780 - 1740 ) MET·min·wk(-1 ) , respectively relative to the decrease in the control groups . The buddy peer support intervention significantly improved mean aerobic fitness ( 12 % [ 95 % CI = 4%-21 % ] ) and reduced both body fat ( -0.6 % [ 95 % CI = -1.1 % to 0.0 % ] ) and time to complete the 2.5-m get-up- and -go test ( -0.27 [ 95 % CI = -0.53 to -0.01 ] s ) . No other improvements in the cardiovascular disease risk factors were observed . The combination of motivational tools was no better than the individual interventions . CONCLUSIONS Both motivational interventions increased physical activity levels , and the buddy style improved fitness . These tools could be useful adjuncts in the prevention of obesity and age-related complications BACKGROUND Recent r and omized controlled trials indicated that exercise training for elderly significantly increased their physical fitness . However , very few studies have examined changes in physical activity after exercise training . The purpose of this study was to investigate whether six-month exercise training for older adults can increase and maintain their physical activity in daily life . METHODS Sixty-two men and women aged 60 to 81 years ( mean age 67.1 years ) , living in communities , were r and omly allocated into an exercise group ( n = 32 ) or a control group ( n = 33 ) . The intervention started in April 1998 and lasted for 25 weeks . The exercise regimen consisted of endurance training and resistance exercises in a two-hour class conducted at least twice a week . The subjects completed a physical activity diary at each pre-intervention ( March 1998 ) , post-intervention ( September 1998 ) and follow-up ( April 1999 ) measurement of physical activity . Physical activity , expressed as total daily energy expenditure , was calculated by multiplying the amount of time spent in each activity and the corresponding METs . RESULTS Total daily energy expenditure significantly increased from 40.8 kcal/kg/day to 43.5 kcal/kg/day in the exercise group ( p = 0.03 ) , but did not change in the control group . At the follow-up measurement , the mean total daily energy expenditure in the exercise group remained significantly higher , by 1.7 kcal/kg/day , than that at the pre-intervention ( p = 0.05 ) . CONCLUSIONS This r and omized controlled trial indicated that exercise training for elderly was effective in increasing physical activity in daily life Background The aim of the present research is to conduct a fully powered explanatory trial to evaluate the efficacy of a brief self-regulation intervention to increase walking . The intervention will be delivered in primary care by practice nurses ( PNs ) and Healthcare Assistants ( HCAs ) to patients for whom increasing physical activity is a particular priority . The intervention has previously demonstrated efficacy with a volunteer population , and subsequently went through an iterative process of refinement in primary care , to maximise acceptability to both providers and recipients . Methods / Design This two arm cluster r and omised controlled trial set in UK general practice s will compare two strategies for increasing walking , assessed by pedometer , over six months . Patients attending practice s r and omised to the self-regulation intervention arm will receive an intervention consisting of behaviour change techniques design ed to increase walking self-efficacy ( confidence in ability to perform the behaviour ) , and to help people translate their " good " intentions into behaviour change by making plans . Patients attending practice s r and omised to the information provision arm will receive written material s promoting walking , and a short unstructured discussion about increasing their walking . The trial will recruit 20 PN/HCAs ( 10 per arm ) , who will be trained by the research team to deliver the self-regulation intervention or information provision control intervention , to 400 patients registered at their practice s ( 20 patients per PN/HCA ) . This will provide 85 % power to detect a mean difference of five minutes/day walking between the self-regulation intervention group and the information provision control group . Secondary outcomes include health services costs , and intervention effects in sub-groups defined by age , ethnicity , gender , socio-economic status , and clinical condition . A mediation analysis will investigate the extent to which changes in constructs specified by the Theory of Planned Behaviour lead to changes in objective ly assessed walking behaviour . Discussion This trial addresses the current lack of evidence for interventions that are effective at increasing walking and that can be offered to patients in primary care . The intervention being evaluated has demonstrated efficacy , and has been through an extensive process of adaptation to ensure acceptability to both provider and recipient , thus optimising fidelity of intervention delivery and treatment receipt . It therefore provides a strong test of the hypothesis that a self-regulation intervention can help primary care patients increase their walking . Trial registration Current Controlled Trials IS RCT PURPOSE We compared the effectiveness of 2 physical activity prescriptions delivered in primary care — the st and ard time-based Green Prescription and a pedometer step-based Green Prescription — on physical activity , body mass index ( BMI ) , blood pressure , and quality of life in low-active older adults . METHODS We undertook a r and omized controlled trial involving 330 low-active older adults ( aged = 65 years ) recruited through their primary care physicians ’ patient data bases . Participants were r and omized to either the pedometer step-based Green Prescription group ( n = 165 ) or the st and ard Green Prescription group ( n = 165 ) . Both groups had a visit with the primary care practitioner and 3 telephone counseling sessions over 12 weeks aim ed at increasing physical activity . Outcomes were the changes in physical activity ( assessed with the Auckl and Heart Study Physical Activity Question naire ) , blood pressure , BMI , quality of life ( assessed with the 36-Item Short Form Health Survey ) , physical function status ( assessed with the Short Physical Performance Battery ) , and falls over a 12-month period . RESULTS Of the patients invited to participate , 57 % responded . At 12 months , leisure walking increased by 49.6 min/wk for the pedometer Green Prescription compared with 28.1 min/wk for the st and ard Green Prescription ( P=.03 ) . For both groups , there were significant increases across all physical activity domains at 3 months ( end of intervention ) that were largely maintained after 12 months of follow-up . BMI did not change in either group . Significant improvements in blood pressure were observed for both groups without any differences between them . CONCLUSIONS Pedometer use result ed in a greater increase in leisure walking without any impact on overall activity level . All participants increased physical activity , and on average , their blood pressure decreased over 12 months , although the clinical relevance is unknown OBJECTIVE Low-cost ( e.g. , computer-tailored ) interventions with sustained effects are needed to increase and maintain physical activity in older adults . This study examined the long-term efficacy of 2 computer-tailored physical activity interventions for older adults and its psychosocial and environmental mediators . METHODS A clustered r and omized controlled trial ( N = 1,971 ) was conducted that included 3 research arms : ( a ) basic computer-tailored print intervention , targeting psychosocial mediators ; ( b ) environmentally computer-tailored print intervention , targeting psychosocial and environmental mediators ; and ( c ) no-intervention control group . Interventions were developed using the intervention mapping approach and consisted of 3 computer-tailored letters delivered over 4 months . Question naires assessed the study outcomes ( i.e. , total weekly days and total weekly minutes of physical activity ) at baseline and 12 months . Potential mediators ( i.e. , awareness , attitude , self-efficacy , intention , social influence , intrinsic motivation , self-regulation , and perceived environment ) were assessed at baseline and at 3 or 6 months . RESULTS Multilevel regression analyses revealed that both interventions significantly changed total weekly days of physical activity compared with the control group , but only the environmentally computer-tailored print intervention significantly changed weekly minutes of physical activity . Multiple mediation models showed that the effects of both interventions on weekly days of physical activity were mediated by changes in awareness and intention . CONCLUSIONS Computer-tailored interventions were effective in inducing long-term behavioral changes in physical activity behavior of older adults . Awareness and intention were found to be important mediators of changing daily physical activity and should be included in future computer-tailored intervention studies OBJECTIVES To evaluate and compare the effectiveness and cost-effectiveness of a leisure centre-based exercise programme , an instructor-led walking programme and advice-only in patients referred for exercise by their GPs . DESIGN A single-centre , parallel-group , r and omised controlled trial , consisting of three arms , with the primary comparison at 6 months . SETTING Assessment s were carried out at Copthall Leisure Centre in Barnet , an outer London borough , and exercise programmes conducted there and at three other leisure centres and a variety of locations suitable for supervised walking throughout the borough . PARTICIPANTS Participants were aged between 40 and 74 years , not currently physically active and with at least one cardiovascular risk factor . INTERVENTIONS The 943 patients who agreed to participate in the trial were assessed in cohorts and r and omised to one of the following three arms : a 10-week programme of supervised exercise classes , two to three times a week in a local leisure centre ; a 10-week instructor-led walking programme , two to three times a week ; an advice-only control group who received tailored advice and information on physical activity including information on local exercise facilities . After 6 months the control group were rer and omised to one of the other trial arms . Assessment s took place before r and omisation , at 10 weeks ( in a r and om 50 % sub sample of participants ) , 6 months and 1 year in the leisure centre and walking arms . The control participants were similarly assessed up to 6 months and then reassessed at the same intervals as those initially r and omised to the leisure centre and walking groups . MAIN OUTCOME MEASURES The primary outcome measures were changes in self-reported exercise behaviour , blood pressure , total cholesterol and lipid subfractions . Secondary outcomes included changes in anthropometry , cardiorespiratory fitness , flexibility , strength and power , self-reported lifestyle behaviour , general and psychological health status , quality of life and health service usage . The costs of providing and making use of the service were quantified for economic evaluation . RESULTS There was a net increase in the proportion of participants achieving at least 150 minutes per week of at least moderate activity in the sport/leisure and walking categories in all three study groups : at 6 months , the net increases were 13.8 % in the leisure centre group , 11.1 % in the walking group and 7.5 % in the advice-only group . There were significant reductions in systolic and diastolic blood pressure in all groups at each assessment point compared with baseline . There were also significant and sustained improvements in cardiorespiratory fitness and leg extensor power , and small reductions in total and low-density lipoprotein cholesterol in all groups , but there were no consistent differences between the groups for any parameter over time . All three groups showed improvement in anxiety and mental well-being scores 6 months after the beginning of the trial . Leisure centre and walking groups maintained this improvement at 1 year . There were no differences between groups . Costs to the participants amounted to pound 100 for the leisure centre scheme and pound 84 for the walking scheme , while provider costs were pound 186 and pound 92 , respectively . Changes in overall Short Form 36 scores were small and advice only appeared the most cost-effective intervention . CONCLUSIONS The results of this trial suggest that referral for tailored advice , supported by written material s , including details of locally available facilities , supplemented by detailed assessment s may be effective in increasing physical activity . The inclusion of supervised exercise classes or walks as a formal component of the scheme may not be more effective than the provision of information about their availability . On cost-effectiveness grounds , assessment and advice alone from an exercise specialist may be appropriate to initiate action in the first instance . Subsidised schemes may be best concentrated on patients at higher absolute risk , or with specific conditions for which particular programmes may be beneficial . Walking appears to be as effective as leisure centre classes and is cheaper . Efforts should be directed towards maintenance of increased activity , with proven measures such as telephone support . Further research should include an up date d meta- analysis of published exercise interventions using the st and ardised mean difference approach The aim of the project was to reach inactive people through primary care offices and motivate them to become more active for health purpose s. Physical activity question naires based on the transtheoretical model ( TM ) of behaviour change were h and ed out to every person entering one of five primary care offices . All inactive people were entered into a r and omised controlled trial ( RCT ) . Individuals assigned to the feedback group were given feedback from their physician concerning their physical activity level . In addition , the advice plus group received further advice and stage matched leaflets and was offered a 45-min counselling session . Changes in physical activity behaviour were measured 7 weeks as well as 14 months after the intervention . Physicians and patients alike reacted positively to the project . Ninety percent of patients entering the primary care offices were willing to participate . Ninety percent of inactive people agreed to be entered into the RCT . The follow-up rate in this trial was 82 % at 14 months . At 7 weeks , 35 % of patients in the feedback group were now classified as active and 38 % of patients in the advice plus group . At 14 months , 47 % of the subjects in both groups were active . Inactive people can be reached effectively through primary care offices . Patients receiving feedback from their physician concerning their physical activity level improved their behaviour to the same extent as patients who were given further advice and written material s , and were offered a counselling session Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials . Recent empirical evidence in health care and physical activity promotion context s provides a foundation for testing the utility of a Self Determination Theory (SDT)-based exercise referral consultation . Methods / Design Design : An exploratory cluster r and omised controlled trial comparing st and ard provision exercise on prescription with a Self Determination Theory-based ( SDT ) exercise on prescription intervention . Participants : 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008 . The 13 exercise on prescription sites in Birmingham were r and omised to current practice ( n = 7 ) or to the SDT-based intervention ( n = 6 ) . Outcomes measured at 3 and 6-months : Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall ; physical health : blood pressure and weight ; health status measured using the Dartmouth CO-OP charts ; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score ; motivation and processes of change : perceptions of autonomy support from the advisor , satisfaction of the needs for competence , autonomy , and relatedness via physical activity , and motivational regulations for exercise . Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a st and ard programme and will test the underlying SDT-based process model ( perceived autonomy support , need satisfaction , motivation regulations , outcomes ) via structural equation modelling . Trial registration The trial is registered as Current Controlled trials IS RCT N07682833 OBJECTIVE Computer-tailored and Internet-based interventions to promote physical activity behavior have shown some promise , but only few have been tested among African Americans . We examined the feasibility and efficacy of three 1-year , multiple contact physical activity interventions ( Tailored Internet , Tailored Print , St and ard Internet ) in a sub sample of African American participants ( n = 38 ) enrolled in a r and omized controlled trial . MATERIAL S AND METHODS Participants r and omly assigned to Tailored Internet and Print programs received individually tailored computer expert system feedback delivered via Internet or print . Participants in the St and ard Internet program received access to six currently available physical activity Web sites . Self-reported physical activity was assessed at baseline and 6 and 12 months with the 7-Day Physical Activity Recall . RESULTS Across all participants , physical activity changed from 17.24 min/week ( st and ard deviation [ SD ] = 20.72 ) at baseline to 139.44 min/week ( SD = 99.20 ) at 6 months , to 104.26 min/week ( SD = 129.14 ) at 12 months . According to available consumer satisfaction data ( n = 30 ) , 70 % reported reading most or all of the physical activity information received by Internet or mail . Most participants described the Internet- and print-based physical activity programs as " somewhat " or " very " helpful ( 80 % ) and enjoyable ( 87 % ) . CONCLUSIONS These findings suggest that computer-tailored and Internet-based interventions are able to produce long-term increases in physical activity and associated process variables among African American participants . Future studies with larger numbers of African American participants are needed to determine which of the programs ( Tailored Print , Tailored Internet , St and ard Internet ) are more effective and what program modifications might be helpful in assisting this population in becoming more active BACKGROUND nearly 61 % of older adults do not maintain recommended exercise levels emphasising the need for interventions that promote exercise . OBJECTIVES to compare self-reported exercise behaviour and functional outcomes over 1 year across three groups of older adults : a cognitive-behavioural therapy group , an attention-control education group and a control group . DESIGN r and omised intervention . SETTING community exercise facilities . PARTICIPANTS three hundred and thirty-two older adults ( mean age = 71.8 ± 5.1 years ) . METHODS all three groups received exercise training three times per week for 2 weeks and then one time per week for 8 weeks , during which time the therapy and education groups received their interventions . Blinded data collectors measured follow-up exercise behaviour and functional outcomes at 3-month intervals . RESULTS after controlling for previous year exercise behaviour , results showed that relative to the control group , the therapy and education groups increased their strengthening exercises over time ( 0.05 and 0.06 h/week higher , respectively ) ; only the therapy group 's change was significant . Also , relative to the control group , the therapy and education groups significantly reduced their 6-min walking distances over time ( -1.6 m , P = 0.030 and -1.5 m , P = 0.026 , respectively ) . CONCLUSIONS although the therapy group increased their strength training , they reduced their 6-min walking distance Objective Swimming is often recommended in the prevention and treatment of hypertension . Few studies have investigated the effect of swimming training on blood pressure ( BP ) . Our objective was to evaluate 6 months of supervised moderate swimming or walking on BP in previously sedentary , normotensive , older women . Design Women aged 50–70 years ( n = 116 ) were r and omly assigned to a supervised 6-month swimming or walking programme . They were further r and omized to receive usual care or a behavioural intervention package . Methods Exercise comprised 3 sessions/week with a warm-up , cool down , and 30-min of moderate intensity walking or swimming . BP was recorded for 20 min supine , and 5 min st and ing . Assessment s were made at 0 and 6 months . Results At baseline , mean supine BP ( ± SD ) was 115.7 ± 1.3/66.8 ± 0.7 mmHg . Swimming improved swim distance by 78.1 m ( 29.3 % ) [ 95 % confidence interval ( CI ) ; 66.7 , 89.4 ] and walk time by 0.58 min ( 3.8 % ) ( 0.41 , 0.74 ) . Walking decreased walk time by 1.0 min ( 6.5 % ) ( 0.81 , 1.19 ) . After adjustment for initial BP , age , hypertension treatment status and change in weight , swimming increased supine and st and ing systolic BP relative to walking by 4.4 mmHg ( 1.2 , 7.5 ) ( P = 0.008 ) and 6.0 mmHg ( 2.6 , 9.5 ) ( P = 0.001 ) , respectively . Supine and st and ing diastolic BP increased by 1.4 mmHg ( −0.14 , 3.0 ) ( P = 0.07 ) and 1.8 mmHg ( −0.02 , 3.5 ) ( P = 0.05 ) , respectively . Conclusion Relative to moderately paced walking , regular swimming significantly elevates BP in previously sedentary , normotensive , older women . This finding may have important implication s for exercise prescription in older subjects BACKGROUND Physician counseling of patients to increase physical activity has had limited success in changing behavior . Providing organizational support to primary care providers and their patients may increase effectiveness . OBJECTIVE This study evaluates the effectiveness of a telephone-based intervention to increase physical activity among patients who exercised < 15 minutes daily and wanted to increase their physical activity over a 6-month period . DESIGN This was a r and omized controlled trial , conducted from 1997 to 1998 , of 316 patients aged 18 to 65 who were recruited from a mailed health risk assessment . Baseline and 6-month post-intervention telephone assessment s were conducted by telephone . SETTING One family physician 's patients in a suburban community . INTERVENTION Three sessions of telephone-delivered motivational counseling . MAIN OUTCOME MEASURES Physical activity score ( 11-item Physician-Based Assessment and Counseling for Exercise [ PACE ] ) 6 months after the intervention . RESULTS After adjusting for baseline exercise , there was a significantly higher level of self-reported exercise among individuals r and omized to the intervention at the 6-month follow-up . The mean level of activity at follow-up for the intervention group was a PACE score of 5.37 , compared to 4.98 in the control group ( p<0.05 ) . In the secondary analysis , which was limited to individuals who received the intervention , the effect was stronger ( PACE score of 5.58 compared to 4.94 , p<0.013 ) . CONCLUSIONS Patients can be recruited using a health-screening question naire to receive a telephone-delivered behavioral intervention to successfully increase their physical activity levels Background In Scotl and , older adults are a key target group for physical activity intervention due to the large proportion who are inactive . The health benefits of an active lifestyle are well established but more research is required on the most effective interventions to increase activity in older adults . The ' West End Walkers 65 + ' r and omised controlled trial aims to examine the feasibility of delivering a pedometer-based walking intervention to adults aged ≥65 years through a primary care setting and to determine the efficacy of this pilot . The study rationale , protocol and recruitment process are discussed in this paper . Methods / Design The intervention consisted of a 12-week pedometer-based graduated walking programme and physical activity consultations . Participants were r and omised into an immediate intervention group ( immediate group ) or a 12-week waiting list control group ( delayed group ) who then received the intervention . For the pilot element of this study , the primary outcome measure was pedometer step counts . Secondary outcome measures of sedentary time and physical activity ( time spent lying/sitting , st and ing or walking ; activPAL ™ monitor ) , mood ( Positive and Negative Affect Schedule ) , functional ability ( Perceived Motor-Efficacy Scale for Older Adults ) , quality of life ( Short-Form ( 36 ) Health Survey version 2 ) and loneliness ( UCLA Loneliness Scale ) were assessed . Focus groups with participants and semi-structured interviews with the research team captured their experiences of the intervention . The feasibility component of this trial examined recruitment via primary care and retention of participants , appropriateness of the intervention for older adults and the delivery of the intervention by a practice nurse . Discussion West End Walkers 65 + will determine the feasibility and pilot the efficacy of delivering a pedometer-based walking intervention through primary care to Scottish adults aged ≥65 years . The study will also examine the effect of the intervention on the well-being of participants and gain an insight into both participant and research team member experiences of the intervention . Trial registration numberIS RCT N : IS RCT OBJECTIVES We assessed the impact of existing best- practice physical activity programs for older adults on physical activity participation and health-related outcomes . METHODS We used a multisite , r and omized trial with 544 older adults ( mean age 66 years ) and measures at baseline , 5 , and 10 months to test the impact of a multiple-component physical activity program compared with results for a control group that did not participate in such a program . RESULTS For adults who participated in a multiple-component physical activity program , we found statistically significant benefits at 5 and 10 months with regard to self-efficacy for exercise adherence over time ( P < .001 ) , adherence in the face of barriers ( P = .01 ) , increased upper- and lower-body strength ( P = .02 , P = .01 ) , and exercise participation ( P = .01 ) . CONCLUSIONS Best- practice community-based physical activity programs can measurably improve aspects of functioning that are risk factors for disability among older adults . US public policy should encourage these inexpensive health promotion programs Background . Counseling sedentary primary care patients can increase physical activity , but whether this approach will increase exercise and fitness in elderly adults with chronic diseases remains to be determined . Methods . After receiving individualized nurse counseling to begin a program of walking for health , 60- to 80-year-old primary care patients were r and omized to one of three levels of telephone contacts over 10 months : ( i ) 20 nurse-initiated calls , ( ii ) 10 nurse-initiated calls plus 10 motivational calls programmed through an automated phone calling system , or ( iii ) no program-initiated phone contacts . Self-reported ( diary ) walking adherence was the primary outcome ; other activity , social support , health quality of life , and measured walking performance , mobility , and body mass index and girths were also assessed during the initiation ( months 1 - 6 ) and maintenance ( months 7 - 10 ) phases of the trial . Results . Average adherence for the 181 participants to the goal of walking at least 20 minutes on 3 or more days per week was 44 % for initiation and 42 % for maintenance . Participants receiving the combination of nurse-initiated personal and automated phone calls walked significantly more frequently than those with no phone contacts . Fitness improved in all three groups ; changes were generally correlated with self-reported walking . Having a companion was associated with more frequent walking . Perceived quality of physical and mental health did not change . Conclusions . Simple and relatively inexpensive nurse contacts can motivate elderly primary care patients to walk for exercise , and this activity is associated with measurable health benefits OBJECTIVE Fantasy realization theory ( Oettingen , 2012 ) proposes that fantasizing about a desired future or dwelling upon negative reality rarely changes behavior whereas mentally contrasting fantasy with reality can be an effective behavior change technique . This is because mental contrasting energizes people to overcome obstacles that st and in the way of their desired future . The present study tested whether mental contrasting promotes rates of physical activity among overweight , middle-aged , and low-SES men . METHOD A r and omized controlled trial was conducted with members of an angling club in the north of Engl and ( N = 467 ) . At baseline , participants completed a postal question naire that measured cognitions about physical activity . The intervention was embedded in the question naire for relevant participants . Behavior was followed up via telephone at 1 month and 7 months postbaseline . The key outcome measure was a vali date d , self-report measure of physical activity ( Godin , Jobin & Bouillon , 1986 ) taken at all three time-points . RESULTS Longitudinal , explanatory , and intention-to-treat analyses each indicated that mental contrasting was effective in enhancing rates of physical activity . Mental contrasting also aided the translation of beliefs about the value and worth of physical activity ( instrumental attitudes ) into action . CONCLUSION Mental contrasting appears to be an effective self-regulatory intervention for promoting physical activity and warrants further tests in health psychology Abstract Objective : To assess the long term effectiveness of the “ green prescription ” programme , a clinician based initiative in general practice that provides counselling on physical activity . Design : Cluster r and omised controlled trial . Practice s were r and omised before systematic screening and recruitment of patients . Setting : 42 rural and urban general practice s in one region of New Zeal and . Subjects : All sedentary 40–79 year old patients visiting their general practitioner during the study 's recruitment period . Intervention : General practitioners were prompted by the patient to give oral and written advice on physical activity during usual consultations . Exercise specialists continued support by telephone and post . Control patients received usual care . Main outcome measures : Change in physical activity , quality of life ( as measured by the “ short form 36 ” ( SF-36 ) question naire ) , cardiovascular risk ( Framingham and D'Agostino equations ) , and blood pressure over a 12 month period . Results : 74 % ( 117/159 ) of general practitioners and 66 % ( 878/1322 ) of screened eligible patients participated in the study . The follow up rate was 85 % ( 750/878 ) . Mean total energy expenditure increased by 9.4 kcal/kg/week ( P=0.001 ) and leisure exercise by 2.7 kcal/kg/week ( P=0.02 ) or 34 minutes/week more in the intervention group than in the control group ( P=0.04 ) . The proportion of the intervention group undertaking 2.5 hours/week of leisure exercise increased by 9.72 % ( P=0.003 ) more than in the control group ( number needed to treat=10.3 ) . SF-36 measures of self rated “ general health , ” “ role physical , ” “ vitality , ” and “ bodily pain ” improved significantly more in the intervention group ( P<0.05 ) . A trend towards decreasing blood pressure became apparent but no significant difference in four year risk of coronary heart disease . Conclusion : Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months . What is already known on this topic Counselling patients in general practice on exercise has result ed in gains in physical fitness and activity , but no health benefits have been found What this study adds Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months without evidence of adverse effects The intervention may reduce blood pressure by an average of 1–2 mm Hg over 12 months No changes in the risk of coronary heart disease were observed The intervention is sustainable in usual general practice Prompting practice staff to deliver the intervention may have increased its Background Since many individuals who initiate physical activity programs are highly likely to return to a sedentary lifestyle , innovative strategies to efforts to increase the number of physically active older adults who successfully maintain beneficial levels of PA for a substantial length of time are needed . Methods / Design The Keep Active Minnesota Trial is a r and omized controlled trial of an interactive phone- and mail-based intervention to help 50–70 year old adults who have recently increased their physical activity level , maintain that activity level over a 24-month period in comparison to usual care . Baseline , 6 , 12 , and 24 month measurement occurred via phone surveys with kilocalories expended per week in total and moderate-to-vigorous physical activity ( CHAMPS Question naire ) as the primary outcome measures . Secondary outcomes include hypothesized mediators of physical activity change ( e.g. , physical activity enjoyment , self-efficacy , physical activity self-concept ) , body mass index , and depression . Seven day accelerometry data were collected on a sub- sample of participants at baseline and 24-month follow-up . Discussion The Keep Active Minnesota study offers an innovative approach to the perennial problem of physical activity relapse ; by focusing explicitly on physical activity maintenance , the intervention holds considerable promise for modifying the typical relapse curve . Moreover , if shown to be efficacious , the use of phone- and mail-based intervention delivery offers potential for widespread dissemination . Trial registration Clinical Trials.gov Identifier : NCT00283452 Objective To assess the effectiveness of a primary care based programme of exercise on prescription among relatively inactive women over a two year period . Design R and omised controlled trial . Setting 17 primary care practice s in Wellington , New Zeal and Participants 1089 women aged 40 - 74 not undertaking 30 minutes of moderate intensity physical activity on at least five days of the week Intervention Brief physical activity intervention led by nurse with six month follow-up visit and monthly telephone support over nine months . Main outcome measure Physical activity assessed at baseline and 12 and 24 months . Secondary outcomes were quality of life ( SF-36 ) , weight , waist circumference , blood pressure , concentrations of fasting serum lipids , glycated haemoglobin ( HbA1c ) , glucose , insulin , and physical fitness . Results Mean age was 58.9 ( SD 7 ) years . Trial retention rates were 93 % and 89 % at 12 and 24 months , respectively . At baseline , 10 % of intervention participants and 11 % of control participants were achieving 150 minutes of at least moderate intensity physical activity a week . At 12 months rates increased to 43 % and 30 % and at 24 months to 39.3 % and 32.8 % ( P<0.001 ) , respectively . SF-36 physical functioning ( P=0.03 ) and mental health ( P<0.05 ) scores improved more in intervention compared with control participants , but role physical scores were significantly lower ( P<0.01 ) . There were no significant differences in clinical outcomes . More falls ( P<0.001 ) and injuries ( P=0.03 ) were recorded in the intervention group . Conclusions This programme of exercise on prescription increased physical activity and quality of life over two years , although falls and injuries also increased . This finding supports the use of exercise on prescription programmes as part of population strategies to reduce physical inactivity . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) ANZCTRN012605000490673 Background Increasing prevalence of obesity and disorders associated with sedentary living constitute a major global public health problem . While previous evaluations of interventions to increase physical activity have involved communities or individuals with established disease , less attention has been given to interventions for individuals at risk of disease . Methods / design ProActive aims to evaluate the efficacy of a theoretical , evidence - and family-based intervention programme to increase physical activity in a sedentary population , defined as being at-risk through having a parental family history of diabetes . Primary care diabetes or family history registers were used to recruit 365 individuals aged 30–50 years , screened for activity level . Participants were assigned by central r and omisation to three intervention programmes : brief written advice ( comparison group ) , or a psychologically based behavioural change programme , delivered either by telephone ( distance group ) or face-to-face in the family home over one year . The protocol -driven intervention programme is delivered by trained facilitators , and aims to support increases in physical activity through the introduction and facilitation of a range of self-regulatory skills ( e.g. goal setting ) . The primary outcome is daytime energy expenditure and its ratio to resting energy expenditure , measured at baseline and one year using individually calibrated heart rate monitoring . Secondary measures include self-report of individual and family activity , psychological mediators of behaviour change , physiological and biochemical correlates , acceptability , and costs , measured at baseline , six months and one year . The primary intention to treat analysis will compare groups at one-year post r and omisation . Estimation of the impact on diabetes incidence will be modelled using data from a parallel ten-year cohort study using similar measures . Discussion ProActiveis the first efficacy trial of an intervention programme to promote physical activity in a defined high-risk group accessible through primary care . The intervention programme is based on psychological theory and evidence ; it introduces and facilitates the use of self-regulatory skills to support behaviour change and maintenance . The trial addresses a range of method ological weaknesses in the field by careful specification and quality assurance of the intervention programme , precise characterisation of participants , year-long follow-up and objective measurement of physical activity . Due to report in 2005 , ProActivewill provide estimates of the extent to which this approach could assist at-risk groups who could benefit from changes in behaviours affecting health , and inform future pragmatic trials Background Declining physical activity is associated with a rising burden of global disease . There is little evidence about effective ways to increase adherence to physical activity . Therefore , interventions are needed that produce sustained increases in adherence to physical activity and are cost-effective . The purpose is to assess the effectiveness of a primary care physical activity intervention in increasing adherence to physical activity in the general population seen in primary care . Method and design R and omized controlled trial with systematic r and om sampling . A total of 424 subjects of both sexes will participate ; all will be over the age of 18 with a low level of physical activity ( according to the International Physical Activity Question naire , IPAQ ) , self-employed and from 9 Primary Healthcare Centres ( PHC ) . They will volunteer to participate in a physical activity programme during 3 months ( 24 sessions ; 2 sessions a week , 60 minutes per session ) . Participants from each PHC will be r and omly allocated to an intervention ( IG ) and control group ( CG ) . The following parameters will be assessed pre and post intervention in both groups : ( 1 ) health-related quality of life ( SF-12 ) , ( 2 ) physical activity stage of change ( Prochaska 's stages of change ) , ( 3 ) level of physical activity ( IPAQ-short version ) , ( 4 ) change in perception of health ( vignettes from the Cooperative World Organization of National Colleges , Academies , and Academic Associations of Family Physicians , COOP/WONCA ) , ( 5 ) level of social support for the physical activity practice ( Social Support for Physical Activity Scale , SSPAS ) , and ( 6 ) control based on analysis ( HDL , LDL and glycated haemoglobin ) . Participants ' frequency of visits to the PHC will be registered over the six months before and after the programme . There will be a follow up in a face to face interview three , six and twelve months after the programme , with the reduced version of IPAQ , SF-12 , SSPAS , and Prochaska 's stages . Discussion The pilot study showed the effectiveness of an enhanced low-cost , evidence -based intervention in increased physical activity and improved social support . If successful in demonstrating long-term improvements , this r and omised controlled trial will be the first sustainable physical activity intervention based in primary care in our country to demonstrate long-term adherence to physical activity . Trial Registration A service of the U.S. National Institutes of Health . Developed by the National Library of Medicine . Clinical Trials.gov ID : NCT00714831 BACKGROUND Regular physical activity produces beneficial effects on health , but the exercise prescription needed to improve cardiovascular disease risk factors in free-living sedentary individuals remains unclear . METHODS Sedentary adults ( N = 492 , 64.0 % women ) were r and omized to 1 of 4 exercise-counseling conditions or to a physician advice comparison group . The duration ( 30 minutes ) and type ( walking ) of exercise were held constant , while exercise intensity and frequency were manipulated to form 4 exercise prescriptions : moderate intensity-low frequency , moderate intensity-high frequency ( HiF ) , hard intensity (HardI)-low frequency , and HardI-HiF. Comparison group participants received physician advice and written material s regarding recommended levels of exercise for health . Outcomes included 6- and 24-month changes in cardiorespiratory fitness ( maximum oxygen consumption ) , high-density lipoprotein cholesterol ( HDL-C ) level , and the total cholesterol-HDL-C ratio . RESULTS At 6 months , the HardI-HiF , HardI-low-frequency , and moderate-intensity-HiF conditions demonstrated significant increases in maximum oxygen consumption ( P < .01 for all ) , but only the HardI-HiF condition showed significant improvements in HDL-C level ( P < .03 ) , total cholesterol-HDL-C ratio ( P < .04 ) , and maximum oxygen consumption ( P < .01 ) compared with physician advice . At 24 months , the increases in maximum oxygen consumption remained significantly higher than baseline in the HardI-HiF , HardI-low-frequency , and moderate-intensity-HiF conditions and in the HardI-HiF group compared with physician advice ( P < .01 for all ) , but no significant effects on HDL-C level ( P = .57 ) or total cholesterol-HDL-C ratio ( P = .64 ) were observed . CONCLUSIONS Exercise counseling with a prescription for walking at either a HardI or a HiF produced significant long-term improvements in cardiorespiratory fitness . More exercise or the combination of HardI plus HiF exercise may provide additional benefits , including larger fitness changes and improved lipid profiles Background Despite the significant health benefits of regular physical activity , approximately half of American adults , particularly women and minorities , do not meet the current physical activity recommendations . Mobile phone technologies are readily available , easily accessible and may provide a potentially powerful tool for delivering physical activity interventions . However , we need to underst and how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women . The purpose of this paper is to describe the study design and protocol of the mPED ( mobile phone based physical activity education ) r and omized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions . Methods A r and omized controlled trial ( RCT ) with three arms ; 1 ) PLUS ( 3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention ) , 2 ) REGULAR ( 3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention ) , and 3 ) CONTROL ( pedometer only , but no intervention will be conducted ) . A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be r and omized into one of the three groups . The mobile phone serves as a means of delivering the physical activity intervention , setting individualized weekly physical activity goals , and providing self-monitoring ( activity diary ) , immediate feedback and social support . The mobile phone also functions as a tool for communication and real-time data capture . The primary outcome is objective ly measured physical activity . Discussion If efficacy of the intervention with a mobile phone is demonstrated , the results of this RCT will be able to provide new insights for current behavioral sciences and mHealth . Trial Registration Clinical Background To our knowledge , no studies have aim ed at improving the PA level in south Asian immigrant men residing in Western countries , and few studies have considered the relevance of SCT constructs to the PA behaviour of this group in the long term . The observed low physical activity ( PA ) level among south Asian immigrants in Western countries may partly explain the high prevalence of cardiovascular diseases ( CVD ) and type 2 diabetes ( T2D ) in this group . We have shown previously in a r and omised controlled trial , the Physical Activity and Minority Health study ( PAMH ) that a social cognitive based intervention can beneficially influence PA level and subsequently reduce waist circumference and insulin resistance in the short-term . In an extended follow-up of the PAMH study : we aim ed 1 ) to determine if the intervention produced long-term positive effects on PA level six months after intervention ( follow-up 2 ( FU2 ) ) , and 2 ) to identify the social cognitive mediators of any intervention effects . Methods Physically inactive Pakistani immigrant men ( n = 150 ) who were free of CVD and T2D were r and omly assigned to a five months PA intervention or a control group . Six months after the intervention ended , we telephoned all those who attended FU1 and invited them for a second follow-up test ( FU2 ) ( n = 133 ) . PA was measured using ActiGraph accelerometers . Statistical differences between groups were determined by use of ANCOVA . Results Significant differences ( baseline to FU2 ) between the groups were found for all PA variables ( e.g. , total PA level , sedentary time , PA intensity ) . Support from family and outcome expectancies increased more in the intervention group compared with the control group . Self-efficacy did not differ significantly between groups . Conclusions Our results show that a multi component PA programme can increase PA over the short and long term in a group of immigrant Pakistani men . However , we could not identify the factors that mediated these changes in PA . Protocol ID07112001326 , NCT ID : BACKGROUND Despite well-known benefits of physical activity for older adults , about two thirds are underactive . Community-based programs are needed to facilitate increased physical activity . We examine the effectiveness of CHAMPS II , an inclusive , choice-based physical activity promotion program to increase lifetime physical activity levels of seniors . CHAMPS guided participants to choose activities that took into account their health , preferences , and abilities . It offered information on ways for them to exercise safely , motivate themselves , overcome barriers , and develop a balanced exercise regimen . METHODS A 1-year r and omized controlled trial was conducted with physically underactive seniors in a multispecialty group practice . Changes in self-reported physical activity by group were evaluated using ANCOVA , controlling for age and sex . RESULTS Of 173 r and omized subjects , 164 ( 95 % ) completed the trial . Subjects were aged 65 to 90 years ( M = 74 , SD = 6 ) ; 66 % were female . The intervention group increased estimated caloric expenditure by 487 calories/week in moderate ( or greater ) intensity activities ( MET > /= 3.0 ; p < .001 ) and by 687 calories/week in physical activities of any intensity ( p < .001 ) . Control group changes were negligible . Between-group analyses found that the changes were significantly different in both measures ( p values < .05 ) . Overweight persons especially benefited from this program . The program was as effective for women , older adults ( 75 + ) , and those who did not set aside time to exercise at baseline . CONCLUSIONS The program led to meaningful physical activity increases . Individually tailored programs to encourage lifestyle changes in seniors may be effective and applicable to health care and community setting Objective —To investigate the impact of a simple written prescription for physical activity given by a general practitioner and the effect of supplementing this with mailed information material s about physical activity . Methods —A controlled trial was conducted in 27 general practice s in New South Wales , Australia . Subjects were sequential routine care patients between 25 and 65 years old . Controls ( n = 386 ) were recruited first , and intervention subjects two weeks later . Intervention subjects were r and omised to receive a prescription only ( n = 380 ) or a prescription plus a mailed booklet ( n = 376 ) . Self reported physical activity levels were measured by interview at baseline , 6–10 weeks , and seven to eight months . Results —By intention to treat , the average changes in minutes of total physical activity did not differ significantly between the groups . Inactive people in the prescription plus supplementary booklet group were significantly more likely than controls to report an increase in their physical activity by at least 60 min/week after 6–10 weeks ( odds ratio 1.58 , 95 % confidence interval 1.06 to 2.35 ) . No significant short term improvements in self reported activity were shown in the prescription only group . In the supplemented group , the proportion reporting an increase in physical activity to 3344 kJ/week at 6–10 weeks was not significant , and neither intervention group showed significant increases in any of the outcome measures at seven to eight months by intention to treat . Treatment received analysis showed greater improvements in intervention groups , especially the prescription plus booklet group , in which the odds of inactive people in this group reporting increased activity became significant at seven to eight months . Conclusions —A prescription for physical activity from a general practitioner , supplemented by additional written material s , can lead to modest short term improvements in self reported physical activity levels among inactive patients . A prescription alone was found not to be effective BACKGROUND Physical activity interventions tailored to individual characteristics and delivered via print produce greater increases in activity compared with nontailored interventions and controls . Using the Internet to deliver a tailored physical activity intervention offers an alternative to print that might be available to larger population s at a lower cost . METHODS Participants ( N=249 adults ; mean [ SD ] age , 44.5 [ 9.3 ] years ; and mean [ SD ] body mass index [ calculated as weight in kilograms divided by height in meters squared ] , 29.4 [ 6.1 ] ) were r and omized to 1 of 3 physical activity interventions : ( 1 ) motivationally tailored Internet ( tailored Internet , n=81 ) , ( 2 ) motivationally tailored print ( tailored print , n=86 ) ; and ( 3 ) 6 research er-selected Web sites available to the public ( st and ard Internet , n=82 ) . Participants in the tailored Internet and tailored print arms received the same tailored intervention content . Participants were assessed at baseline and at 6 and 12 months . RESULTS At 6 months , participants in the tailored print arm reported a median of 112.5 minutes of physical activity per week , those in the tailored Internet arm reported 120.0 minutes , and those in the st and ard Internet arm reported 90.0 minutes ( P=.15 ) . At 12 months , the physical activity minutes per week were 90.0 , 90.0 , and 80.0 for those in the tailored print , tailored Internet , and st and ard Internet arms , respectively ( P=.74 ) . Results indicated no significant differences between the 3 arms . CONCLUSIONS The use of tailored Internet , tailored print , and st and ard Internet as part of a behavior change program increased physical activity behavior similarly . Because the use of the Internet was not different from the print-based intervention , this may be an opportunity to reach more sedentary adults in a more cost-effective way . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00200317 BACKGROUND In the U.S. , Latinos report particularly high levels of inactivity and related chronic illnesses and are in need of intervention . Thus , the purpose of the current study was to culturally and linguistically adapt an empirically supported , individually tailored physical activity print intervention for Latinos and then conduct an RCT of the modified program . DESIGN An RCT was conducted . SETTING / PARTICIPANTS The sample included 93 overweight/obese ( 80 % ) Latinas with low income and acculturation . INTERVENTION Data were collected in 2007 - 2008 and analyzed by intent-to-treat in 2009 . Participants were r and omly assigned to either ( 1 ) a culturally and linguistically adapted physical activity intervention ( Seamos Activas ) or ( 2 ) a wellness contact control condition . MAIN OUTCOME MEASURES Self-report physical activity , as measured pre- and post-intervention ( 6 months , 87 % retention ) by the 7-Day Physical Activity Recall . RESULTS Moderate-intensity ( or greater ) physical activity increased from an average of 16.56 minutes/week ( SD=25.76 ) at baseline to 147.27 ( SD=241.55 ) at 6 months in the intervention arm ( n=45 ) , and from 11.88 minutes/week ( SD=21.99 ) to 96.79 ( SD=118.49 ) in the wellness contact control arm ( n=48 ) . No between-group differences were seen in overall physical activity . Intervention participants reported significantly greater increases in cognitive ( F[1 , 91]=9.53 , p=0.003 ) and behavioral processes of change ( F[1 , 91]=8.37 , p=0.005 ) and available physical activity supplies and equipment at home ( F[1 , 91]=4.17 , p=0.04 ) than control participants . CONCLUSIONS Results supported the hypothesized feasibility , acceptability , and preliminary efficacy of individually tailored physical activity print interventions among Latinas . Although more research is needed to corroborate these findings , such high-reach , low-cost approaches have great potential to positively affect public health . TRIAL REGISTRATION NCT00724165 BACKGROUND The study examined the effectiveness of primary -care counseling using a 2-pronged intervention to increase physical activity ( PA ) in a southeastern US city . METHODS Two hundred thirty-seven patients were r and omly assigned to 1 of 3 groups ( experimental [ counseling and educational map ] , control group # 1 [ counseling only ] , or control # 2 [ st and ard care ] ) to identify PA differences . The experimental group received physician counseling and an educational map highlighting accessible recreational facilities within a 2-mile radius of the health center . RESULTS Patients in the experimental group increased their weekly PA in comparison with patients in the controls . Significant differences were observed for patients between groups for PA ( F = 7.648 , df 3,423 , P = .000 ) , PA x visits interaction ( F = 5.500 , df 3,423 , P = .001 ) , and the PA x group interaction ( F = 3.068 , df 6,848 , P = .006 ) . CONCLUSIONS This approach can perhaps increase the PA levels of underserved adults Purpose . To determine the efficacy of community-based , culturally tailored exercise intervention on the moderate and vigorous physical activity and physiologic outcomes of low-income Latino women ( Latinas ) . Design . A r and omized trial contrasted safety education to an aerobic dance intervention . Setting . Interventions were held in a “ store-front ” exercise site near a community clinic . Subjects . Sedentary low-income Latinas ( N = 151 ; 18—55 years ; 70 % overweight/obese ) were recruited . Retention was 91 % for follow-up measures . Intervention . Three sessions per week of supervised aerobic dance were provided for 6 months . Controls attended 18 safety education sessions over 6 months . Measures . Physical activity and aerobic fitness ( VO2max ) were primary outcomes . Results . Participants in the exercise group reported more vigorous exercise ( p < .001 ) and walking ( p = .005 ) at post-test than controls . Aerobic dance and unsupervised activity result ed in a five-fold greater increase in relative VO2max compared with controls ( p < .001 ) . Although exercise and fitness decreased at follow-up , vigorous exercise ( p = .001 ) and relative VO2max ( p < .001 ) remained higher in the exercise group , suggesting maintenance at 1 year . Conclusion . Culturally tailored aerobic dance can increase vigorous physical activity , possibly generalizing to walking , and the combination can improve cardiorespiratory fitness in low-income , overweight , sedentary Latinas OBJECTIVE To enhance a previously efficacious individually tailored physical activity ( PA ) promotion intervention by adding theoretical constructs to the tailored feedback . DESIGN We r and omly assigned 248 healthy , underactive ( moderate to vigorous physical activity [ MVPA ] min/week < 90 ) adults ( mean age = 48.8 years , SD = 10.0 ) to receive either ( a ) a theoretically tailored ( based on 5 constructs from the transtheoretical model and social-cognitive theory [ SCT ] ) print-based PA promotion intervention ( print ) or ( b ) the same theoretically tailored print-based PA promotion intervention plus enhanced tailoring addressing 5 additional SCT constructs ( enhanced print ) . MAIN OUTCOME MEASURE The 7-day physical activity recall administered at baseline , Month 6 , and Month 12 , with outcomes operationalized as percentage achieving 150 min/week of MVPA . RESULTS When controlling for covariates , there was a nonsignificant trend in favor of the enhanced print condition reflecting 46 % and 50 % greater odds of achieving 150 min/week of MVPA at Month 6 and Month 12 , respectively . CONCLUSION Enhanced tailoring based on additional theoretical constructs may result in marginal improvements in physical activity outcomes INTRODUCTION Impact exercise is known to be beneficial for bones , but information regarding its effects on other health aspects is scarce . The aim of this study was to assess the effects of high-impact exercise on physical performance and glucose and lipid profiles . METHODS We performed a 12-month , population -based , r and omized controlled trial with 120 women ( 60 in the exercise group and 60 in the control group ; ages 35 - 40 yr ) . The exercise regimen comprised supervised , progressive , high-impact exercises two to three times per week and an additional home program . Physical activity was continuously recorded using an accelerometer-based method and was analyzed as the daily number of impacts within five acceleration ranges between 0.3 and 9.2 g ( g = acceleration of gravity : 9.81 m x s(-2 ) ) . The changes in physical performance and in glucose and lipid profiles were determined . RESULTS Thirty-nine women in the exercise group and 41 women in the control group completed the study . Maximal oxygen uptake ( 6.2 vs 3.1 mL x kg(-1 ) x min(-1 ) ; P = 0.008 ) and countermovement ( 2.3 vs -0.3 cm ; P < 0.001 ) and static ( 1.4 vs -0.3 cm ; P = 0.004 ) jump heights increased significantly more in the exercise group than in the control group . Exercise training also decreased waist ( -1.1 vs 0.9 cm ; P = 0.048 ) and hip circumference ( -1.0 vs 1.1 cm ; P = 0.037 ) . Total cholesterol and LDL cholesterol decreased significantly more in women , with the highest number of impacts compared with the lowest quartile at intensities exceeding 1.1 g , with differences being up to -0.5 mM ( P = 0.005 ) . Additionally , poor baseline values predicted greater exercise effects . CONCLUSION The moderate-intensity exercise regimen , initially targeted at weight-bearing bones , improved cardiorespiratory fitness , speed-strength , and lipid profiles . In addition to bone health , impact exercise may be recommended for prevention of cardiovascular diseases OBJECTIVE To examine if a website-delivered physical activity intervention , that provides participants with computer-tailored feedback , can improve physical activity in the general population . METHODS Healthy adults ( n=434 ) , recruited from parents and staff of 14 primary and secondary schools in Belgium in the spring of 2005 , were allocated into one of two intervention groups ( receiving intervention with or without repeated feedback ) or a no-intervention control group . Physical activity-levels were self-reported at baseline and at 6 months ( n=285 ) , using a computerized long version of the International Physical Activity Question naire online . Repeated measures analysis of co-variances were used to examine differences between the three groups . RESULTS Intent-to-treat analysis showed significant time by group interaction effects in favor of both intervention groups compared with the control group . Significant increases were found for active transportation ( + 20 , + 24 , + 11 min/week respectively ) and leisure-time physical activity ( + 26 , + 19 , -4 min/week respectively ) ; a significant decrease for minutes sitting on weekdays ( -22 , -34 , + 4 min/day respectively ) . No significant differences were found between both intervention groups . CONCLUSION A website-delivered intervention , including computer-tailoring , was able to increase physical activity when compared to a no-intervention control group . High drop-out rate and the low number of participants who received repeated feedback indicated that engagement and retention are important challenges in e-health studies BACKGROUND There is increasing interest in developing interventions to promote physical activity ( PA ) that do not involve face-to-face contact with health professionals . We developed a fully automated PA counseling system ( telephone-linked communication , TLC-PA ) that was delivered via telephone . DESIGN A r and omized , controlled trial with 298 adult , sedentary members ( mean age , 45.9 years ; 72 % women ; 45 % white ; and 45 % African American ) of a multi-site medical practice . The comparison group ( TLC-Eat ) received an automated intervention promoting healthy eating , which was also delivered via telephone . INTERVENTION The TLC-PA promoted moderate-intensity PA ( MI-PA ) based on the transtheoretical model of behavior change and social cognitive theory . The system was available to participants for 6 months . MAIN OUTCOMES Energy expenditure in MI-PA , proportion of participants who met recommendations for MI-PA , and motivational readiness for PA . MEASURES Self-reports of PA behavior and motivational readiness at baseline , 3 months , and 6 months . RESULTS At 3 months , intention-to-treat analyses showed that the TLC-PA group was more likely to meet recommendations for MI- or vigorous-intensity PA ( VI-PA ) compared to the TLC-Eat group ( TLC-PA=26 % vs TLC-Eat=19.6 % , p=0.04 ) . Among study completers , TLC-PA subjects reported significantly higher daily kilocalorie energy expenditure in MI-PA ( 2.3 kcal/kg/d vs 2.0 kcal/kg/d , p=0.02 ) ; a larger proportion met recommendations for MI- or VI-PA ( 31.2 % vs 21.3 % , p=0.02 ) and were in more advanced stages of motivational readiness than TLC-Eat subjects ( TLC-PA=52.5 % vs TLC-Eat=42.2 % , p=0.04 ) . Results were not maintained at 6 months . The proportion of TLC-PA users decreased significantly over the intervention period . CONCLUSIONS A fully automated counseling system had positive short-term effects on PA among sedentary adults . Lack of maintenance of effects may be due to a decrease in the number of participants who continued to use the system This article describes the equivalency testing results of a 12-week behavior change program on targeted determinates of physical activity ( PA ) and self-reported health status . Participants ( n = 192 ) were r and omized to face-to-face , combined Internet and face-to-face , and Internet-only groups . Equivalency testing was used to examine differences and statistical equivalency across groups for all outcome measures ( social support , self-efficacy , perceived health status , and motivational readiness for PA ) . Participants were assessed at baseline , postintervention , and 2 and 5 months postintervention . Motivational readiness for PA increased across all groups . The face-to-face and combined groups showed changes in social support ; however , they were not statistically different and were equivalent . There were no changes in self-efficacy or physical health status . Overall face-to-face and the Internet delivery modes show similar results . If Internet-based programs can be shown to be as effective as face-to-face , they may in turn be a more efficient and cost-effective delivery method OBJECTIVE To determine the effects of adding stages of change-based counseling to an exercise prescription for older , sedentary adults in family practice . DESIGN The Step Test Exercise Prescription Stages of change counseling study was a 12-month cluster r and omized trial . SETTING Forty family practice s in 4 regions of Canada . PARTICIPANTS Healthy , community-dwelling men ( 48 % ) and women ( 52 % ) with a mean ( SD ) age of 64.9 ( 7.1 ) years ( range 55 to 85 years ) . There were a total of 193 participants in the intervention group and 167 in the control group . INTERVENTION Intervention physicians were trained to deliver a tailored exercise prescription and a transtheoretical behaviour change counseling program . Control physicians were trained to deliver the exercise prescription alone . MAIN OUTCOME MEASURES Predicted cardiorespiratory fitness , measured by predicted maximal oxygen consumption ( pVO2max ) , and energy expenditure , measured by 7-day physical activity recall . RESULTS Mean increase in pVO2max was significant for both the intervention ( 3.02 [ 95 % confidence interval 2.40 to 3.65 ] mL/kg/min ) and control ( 2.21 [ 95 % confidence interval 1.27 to 3.15 ] mL/kg/min ) groups at 12 months ( P < .001 ) ; however , there was no difference between groups . Women in the intervention group improved their fitness significantly more than women in the control group did ( 3.20 vs 1.23 mL/kg/min ) . The intervention group had a 4-mm Hg reduction in systolic blood pressure , while the control group 's mean reduction was 0.4 mm Hg ( P < .001 ) . The mean ( SD ) energy expended significantly increased and was higher in the intervention group than in the control group ( 69.06 [ 169.87 ] kcal/d vs -6.96 [ 157.06 ] kcal/d , P < .006 ) . Practice setting characteristics did not significantly affect the primary outcomes . CONCLUSION The Step Test Exercise Prescription Stages of change exercise and behavioural intervention improved fitness and activity and lowered systolic blood pressure across a range of Canadian practice s , but this was not significantly different from the control group , which received only the exercise prescription . Women in the intervention group showed higher levels of fitness than women in the control group did ; men in both groups showed similar improvement The purpose of this paper was to report the physical activity and health outcomes results from the Physical Activity Counselling ( PAC ) trial . Patients ( n = 120 , mean age 47.3 ± 11.1 years , 69.2 % female ) who reported less than 150 min of physical activity per week were recruited from a large community-based Canadian primary care practice . After receiving brief physical activity counselling from their provider , they were r and omized to receive 6 additional patient-centered counselling sessions over 3 months from a physical activity counsellor ( intensive-counselling group ; n = 61 ) , or no further intervention ( brief-counselling group ; n = 59 ) . Physical activity ( self-reported and accelerometer ) was measured every 6 weeks up to 25 weeks ( 12 weeks postintervention ) . Quality of life was also assessed , and physical and metabolic outcomes were evaluated in a r and omly selected subset of patients ( 33 % ) . In the intent-to-treat analyses of covariance , the intensive-counselling group self-reported significantly higher levels of physical activity at 6 weeks ( p = 0.009 ) and 13 weeks ( p = 0.01 ) . There were no differences in self-reported physical activity between the groups after the intervention in the follow-up period , nor was there any increase in accelerometer-measured physical activity . Finally , the intensive-counselling patients showed greater decreases in percent body fat and total fat mass from 13 weeks to 25 weeks . Results for physical activity depended on the method used , with positive short-term results with self-report and no effects with the accelerometers . Between-group differences were found for body composition in that the intensive-counselling patients decreased more . A multisite r and omized controlled trial with a longer intensive intervention and follow-up is warranted This study compared the effects of 3 home-based exercise promotion programs for African Americans . Sixty , sedentary African-American adults were r and omly assigned to either a st and ard behavioral counseling group ( N=22 ) , a culturally sensitive counseling group ( N=20 ) , or a physician advice comparison group ( N=10 ) . The key study outcomes measured at baseline and after 6 months included cardiorespiratory fitness and physical activity . Acculturation was examined as a moderating variable . Participants in all 3 groups reported significant increases in walking , but significant improvements in fitness were observed only in the 2 intervention groups . Participants in the culturally sensitive intervention reported significantly higher levels of exercise social support compared to members of the other 2 groups . These findings show that home-based exercise counseling programs are effective for improving fitness , yet the addition of culturally tailored components may not be sufficient to produce better outcomes than st and ard behavioral counseling PURPOSE We examined the efficacy of an intervention tailored to the individual 's stage of change for exercise adoption on exercise stage of change , physical activity , and physical function in community-dwelling older adults . DESIGN AND METHODS We r and omized participants to a print and telephone intervention or a contact comparison group . Through the use of longitudinal analyses we examined the intervention 's effectiveness in promoting stage progression , altering decisional balance and the processes of change , increasing self-efficacy and physical activity , and improving physical function among older adults who completed the 24-month study ( N = 966 ) . We conducted similar analyses that excluded individuals who were in maintenance at baseline and 24 months . RESULTS At the end of the study , there were no differences in stage progression , self-efficacy , decisional balance , the processes of change , physical activity , or physical function by intervention assignment . When the analyses excluded those participants ( n = 358 ) who were in the maintenance stage for exercise throughout the intervention , we found that , compared with the comparison group , a greater proportion of individuals who received the exercise intervention progressed in stage by 24 months . Conversely , more individuals in the comparison group remained stable or regressed in stage compared with the intervention group . IMPLICATION S Results indicate that a tailored intervention is effective in increasing motivational readiness for exercise in individuals who were in stages of change other than maintenance OBJECTIVES To examine the effectiveness of prescription-based counseling and self-monitoring in the promotion of physical activity in primary health care . METHODS The study was conducted in Finl and during 2003 - 2004 . Physicians from 24 health care units ( N = 67 ) were r and omized to a prescription or a non-prescription group . The patients ( N = 265 ) were assigned to the groups according to their physician . Every other patient of the non-prescription physicians received a pedometer and a physical activity log ( MON ) and feedback about their 5-day-recordings , the rest served as controls ( CON ) . PA was assessed prior and 2 and 6 months after the physician 's appointment with a question naire . RESULTS The mean increase in weekly overall physical activity at 2 months was 1.0 ( 95 % CI 0.0 to 2.0 ) session more in the prescription group than in controls . In at least moderate-intensity physical activity , the mean difference in changes was 0.8 ( 95 % CI 0.1 to 1.5 ) sessions at 2 months and 0.9 ( 95 % CI 0.2 to 1.5 ) sessions at 6 months for the favor of the prescription group . Compared to controls , self-monitoring increased the weekly duration of overall PA at 2 months on average by 217 min ( 95 % CI 23 to 411 ) . CONCLUSIONS Prescription can be recommended as a tool for primary health care physicians to promote physical activity . Self-monitoring with an expert feedback can be useful in increasing especially the weekly duration of overall physical activity in the short term The aim of this study was to assess the effects of implementation intentions on leisure-time physical activity , taking into account the stability of intention . At baseline ( T0 ) , 349 participants completed a psychosocial question naire and were r and omly assigned to implementation intention or control condition . Three months after baseline assessment ( T1 ) , participants in the experimental group were asked to plan where , when , and how they would exercise . Leisure-time physical activity was assessed 3 mo . later ( i.e. , at 6-mo . follow-up ; T2 ) . The intervention had no significant effect on physical activity at 6-mo . follow-up . However , a significant interaction of group and intention stability was observed , with the effect of the intervention on behaviour statistically significant only among those with unstable intention . Intention stability thus moderated the effect of the intervention , i.e. , the intervention was more successful among individuals who needed support to change ( unstable intenders ) BACKGROUND Pedometers have been identified as a potential motivational aid for increasing physical activity , but their efficacy has not been demonstrated in a community-based , non clinical sample . DESIGN A r and omized controlled trial was conducted from August to December 2005 . Analysis was completed in June 2006 . SETTING / PARTICIPANTS Inactive adults aged 30 - 65 years ( n=369 ) recruited from the community . INTERVENTION Comparison of a theoretically based self-help walking program ( WP ) and weekly diaries ( sent by mail ) ; the same walking program with a pedometer ( WPP ) ( also by mail ) ; and a no-treatment control group ( C ) . MEASURES Change in self-reported leisure time in any sports/recreation in the last 3 months , and all- purpose walking ( APW ) for exercise , recreation , and travel , and other moderate , vigorous physical activity in the last week . Proportions meeting physical activity recommendations ( equal to or greater than 150 minutes and equal to or greater than five sessions/week(-1 ) ) were determined . RESULTS A 3-month follow-up interview was conducted with 314 ( 85 % ) participants . Intention-to-treat analyses indicated significance within-group increases of APW and leisure-time walking ( LTW ) , but mean and median sessions and minutes changes were greatest in the WPP group . There were no significant between-group differences in regular LTW ( walked equal to or greater than 5 sessions/week(-1 ) for at least 30 minutes/session ) , but the WPP group increased significantly participation in other sports/recreations and was more likely than the control group to meet physical activity recommendations by all leisure-time physical activity ( adjusted odds ratio=2.40 , 95 % CI=1.17 - 4.93 ) , by APW ( adjusted odds ratio=1.75 95 % CI=0.92 - 3.34 ) and all physical activity ( adjusted odds ratio=1.59 95 % CI=0.92 - 2.79 ) in the last week . CONCLUSIONS Pedometers enhanced the effects of the self-help walking program . This low-cost intervention should be tested for sustainability Background and Objective : Recommendations for physical activity to lower risk of cardiovascular disease ( CVD ) are widely known but not often followed . The purpose of this study was to determine the demographic , lifestyle , and psychosocial variables that predict improved physical activity among participants in a CVD prevention lifestyle intervention trial . Subjects and Methods : Adult family members ( N = 501 ; 66 % female ; 36 % nonwhite ; mean age , 48 years ) of cardiac patients were r and omized to a 1-year special intervention that received education on physical activity or to a control intervention . Demographics , physical activity , stage of change , and CVD risk factors were measured systematic ally at baseline and 1 year ( 94 % follow-up ) . Lipids were analyzed in a core laboratory . Linear regression models were adjusted for confounders . Results : At baseline , 21 % of participants reported exercising more than 3 d/wk , which did not differ by group assignment . The special intervention and control intervention experienced significant increases in physical activity at 1 year with mean physical activity days per week in the special intervention significantly greater than the control intervention ( 2.5 vs 2.0 d/wk , P = .03 ) . Significant predictors of increased physical activity at 1 year were group assignment ( P = .03 ) , female sex ( P = .04 ) , nonminority status ( P < .01 ) , greater readiness to change ( P < .01 ) , and baseline measurements of lower body mass index ( P < .01 ) and waist size ( P < .01 ) , greater diet adherence ( P < .01 ) , higher high-density lipoprotein cholesterol ( P < .01 ) , lower high-sensitivity C-reactive protein ( P = .02 ) , less depression ( P < .01 ) , and higher social support ( P = .03 ) . In multiple regression models , group assignment , female , and nonminority status remained independent predictors of higher physical activity levels at 1 year . Conclusion : Several predictors of improved physical activity levels at 1 year were documented among clinical trial participants . Racial/ethnic minorities and men were significantly less likely to make positive changes and may need more targeted efforts to improve physical activity levels OBJECTIVE To evaluate the effects of a lifestyle intervention and a structured exercise intervention on physical activity in older adults . METHOD Participants were r and omly assigned to a lifestyle intervention ( n=60 ) , including an individualized home-based program supported by phone calls , or to a structured intervention ( n=60 ) consisting of three weekly supervised sessions . Results were compared with a control group ( n=66 ) . Physical activity was measured with self-report question naires , pedometers , and accelerometers before the start ( pretest ) , at the end ( 11 months , posttest ) , and after 23 months ( follow-up ) . The study took place in Belgium from March 2004 until April 2006 . RESULTS At posttest , both intervention groups had significantly increased their total physical activity compared with the control group . At follow-up , the lifestyle group showed significantly larger increases in active transportation and total steps than the control and structured group respectively . There were no longer significant differences between the structured intervention and the control group . CONCLUSIONS The structured and lifestyle interventions were equally effective at the end of the intervention . One year after the intervention the lifestyle group maintained a significant increase in physical activity , which highlights the potential of lifestyle programs in the battle against inactivity in older adults There is compelling evidence supporting the benefits of increased regular physical activity in older adults . The Experience Corps program in Baltimore MD was design ed in part as a community based approach to increasing physical activity that would also appeal to older adults who have historically not utilized health promotion programs . The Baltimore Experience Corps program places older volunteers in public elementary schools for 15 h a week in roles design ed to improve the academic outcomes of children and , simultaneously , increase the physical , cognitive and social activity of volunteers . This paper reports on the change in physical activity levels among older adults associated with participation in the Baltimore Experience Corps . In a pilot r and omized controlled evaluation , older adults were r and omly assigned to Experience Corps ( EC participants ) or a waiting list control group . Ages ranged from 59–86 years , 96 % were African American , 94 % were women , and 84 % had annual incomes less than $ 15,000 . EC participants were required to serve ≥15 h a week . At follow-up after 4–8 months , an analysis of 113 r and omized volunteers revealed 53 % of the EC participants were more active than the previous year by self-report , as compared to 23 % of the controls ( p<0.01 ) . When adjusted for age , gender and education , there was a trend toward increased physical activity in the EC participants as calculated by a kilocalorie per week increase of 40 % , versus a 16 % decrease in the controls ( p=0.49 ) . EC participants who reported “ low activity ” at baseline experienced an average 110 % increase in their physical activity at follow-up . Among the controls who were in the “ low activity ” group at baseline , there was , on average , only a 12 % increase in physical activity ( p=0.03 ) . Among those who were previously active , there was no significant difference ( p=0.30 ) . The pilot results suggest that a high intensity volunteer program that is design ed as a health promotion intervention can lead , in the short-term , to significant improvements in the level of physical activity of previously inactive older adult volunteers Little research exists on the impact of behavior change interventions in disadvantaged communities . We conducted a prospect i ve study to explore the effectiveness of motivational interviewing on physical activity change within a deprived community and the social- psychological and motivational predictors of change in physical activity including stage of change , self-efficacy , social support , and variables from self-determination theory and the theory of planned behavior . Five motivational interviewing counsellors recruited 207 patients and offered motivational interviewing sessions to support physical activity behavior change . At 6-months there were significant improvements in physical activity , stage of change , and social support . A dose – response relationship was evident ; those who attended 2 or more consultations increased their total physical activity , stage of change and family social support more than those who attended just one . Hierarchical regression analyses indicated that number of sessions and change in stage of change predicted 28.4 % of the variance in change in total physical activity and , with social support from friends , 21.0 % of the variance in change walking time . Change in perceived behavioral control and attitudes , friend social support , and number of sessions predicted 16.8 % of the variance in change in vigorous physical activity . Motivational interviewing is an effective approach for promoting physical activity amongst lower socio-economic status groups in the short term . The study demonstrates good translational efficacy , and contributes to a limited number of physical activity interventions targeting low income groups in the UK OBJECTIVE Internet-based physical activity ( PA ) interventions have shown promise , although findings remain equivocal . We used formative research to enhance a previously demonstrated program ( Step into Motion ) with the goal of developing an Internet program poised for dissemination . METHODS We conducted focus groups to identify Internet features targeted to theoretical constructs ( social cognitive theory ) predictive of PA behavior and rated as " useful for increasing PA . " We identified 5 theory-targeted Internet features as useful for increasing PA : ( 1 ) a PA tracking/logging calendar targeting self-monitoring and goal setting ; ( 2 ) geographic mapping tools targeting perceived environment ; ( 3 ) a discussion forum targeting social support ; ( 4 ) exercise videos targeting observational learning ; and ( 5 ) regular up date s of peer PA progress targeting situation . We then tested the efficacy of the enhanced program ( enhanced Internet , EI ; N = 25 ) in relation to publicly available PA Websites ( st and ard Internet , SI ; N = 28 ) among 53 participants in a r and omized controlled trial . RESULTS The EI arm increased PA in relation to the SI arm at 3 months ( 18.4 to 186.0 min/wk vs. 20.9 to 57.3 min/wk ; p = .03 ) but between-groups differences were not observed at 6 months ( 176.8 vs. 133.5 min/wk ; p = .44 ) . EI participants maintained PA from 3 to 6 months ( 186.0 to 176.8 min/wk ) , and the SI group increased PA ( 57.3 to 133.5 min/wk ) . CONCLUSION The EI program was efficacious at improving PA levels in relation to publicly available Websites initially , but differences in PA levels were not maintained at 6 months . Future research should identify Internet features that promote long-term maintenance Objective : To determine whether patterns of exercise adoption by older women would conform to the Transtheoretical Model ( TTM ) of behavior change . Methods : Participants were r and omized into an exercise group ( walk 30 minutes per day , 5 days per week , plus balance exercises twice per week ) or attention control ( health education on topics other than exercise ) . The intervention was conducted over 28 weeks with 1-year follow-up . Results : Participants included 272 sedentary women aged 70 and above . Exercise adoption was higher in the intervention group ( 83 % vs. 17 % among controls ) . After 1 year , 60 % of the intervention group was in action or maintenance , compared to 16 % of the control group . Self-efficacy following the intervention predicted long-term exercise adherence . Discussion : Few studies have addressed longitudinal analysis of the TTM for exercise adoption . Most constructs from the TTM were useful in explaining exercise adoption in older sedentary women OBJECTIVES To determine the effectiveness of a behavior change intervention ( BCI ) with or without a pedometer in increasing physical activity in sedentary older women . DESIGN Prospect i ve r and omized controlled trial . SETTING Primary care , City of Dundee , Scotl and . PARTICIPANTS Two hundred four sedentary women aged 70 and older . INTERVENTIONS Six months of BCI , BCI plus pedometer ( pedometer plus ) , or usual care . MEASUREMENTS PRIMARY OUTCOME change in daily activity counts measured by accelerometry . SECONDARY OUTCOMES Short Physical Performance Battery , health-related quality of life , depression and anxiety , falls , and National Health Service re source use . RESULTS One hundred seventy-nine of 204 ( 88 % ) women completed the 6-month trial . Withdrawals were highest from the BCI group ( 15/68 ) followed by the pedometer plus group ( 8/68 ) and then the control group ( 2/64 ) . After adjustment for baseline differences , accelerometry counts increased significantly more in the BCI group at 3 months than in the control group ( P = .002 ) and the pedometer plus group ( P = .04 ) . By 6 months , accelerometry counts in both intervention groups had fallen to levels that were no longer statistically significantly different from baseline . There were no significant changes in the secondary outcomes . CONCLUSION The BCI was effective in objective ly increasing physical activity in sedentary older women . Provision of a pedometer yielded no additional benefit in physical activity , but may have motivated participants to remain in the trial RATIONALE , AIMS AND OBJECTIVES Systematic review s point to inconclusive evidence that counselling patients in a primary care setting is effective in increasing adults ' physical activity ( PA ) levels . This study evaluates the impact of an innovative physician counselling programme on physicians ' PA counselling behaviour and their patients ' PA levels . METHODS A controlled educational study conducted at six Yale School of Medicine hospitals . Sixty-five internal medicine residents and 316 primary care patients were r and omized to intervention or control groups . Intervention physicians participated in five interactive sessions outlining details of the Pressure System Model , while control physicians received usual residency training . Intervention and control patients ' PA levels and residents counselling behaviour were assessed using a vali date d question naire and compared pre- and post intervention . Data analysis was performed using paired t-tests and repeated measures anova . RESULTS At 6-month follow-up intervention , patients ' PA levels increased significantly from baseline ( 1.77 + /- 0.84 ; P = 0.0376 ) . A similar pattern was observed after 12 months ( 1.94 + /- 0.98 ; P = 0.0486 ) . Control patients ' PA did not change significantly from baseline at 6 or 12 months ( 0.35 + /- 1.00 ; P = 0.7224 and 0.99 + /- 1.52 ; P = 0.5160 , respectively ) . At 12 months , intervention residents provided PA counselling 1.5 times more than they did at baseline ( P < 0.05 ) compared with no significant changes in the control group . CONCLUSIONS The present study has shown that providing residents with a practical tool , enabling them to deal with patients ' barriers and previous failure in behavioural change , is efficacious in increasing PA levels of adult patients BACKGROUND A growing number of the population are using the Internet for health information , such as physical activity ( PA ) . The aim of this study was to examine the effectiveness of delivery modes for a behavior change program targeting PA . METHODS A r and omized trial was conducted with 192 subjects r and omly allocated to either a face-to-face , Internet-mediated , or Internet-only arm of a 12-wk intervention . Subjects included inactive adults with Internet access . The primary outcome variable was self-reported PA , assessed at four time points . RESULTS The results showed no group x time interaction for PA F(6 , 567 ) = 1.64 , p > 0.05 , and no main effect for group F(2 , 189 ) = 1.58 , p > 0.05 . However , a main effect for time F(3 , 567 ) = 75.7 , p < 0.01 was observed for each group . All groups were statistically equivalent immediately post-intervention ( p < 0.05 ) , but not at the follow-up time points ( p > 0.05 ) . The Internet-mediated and Internet-only groups showed similar increases in PA to the face-to-face group immediately post-intervention . CONCLUSIONS This study provides evidence in support of the Internet in the delivery of PA interventions and highlights avenues for future research OBJECTIVE To examine in previously sedentary older women the effects of exercise mode and a behavioural intervention on short and long-term retention and adherence . METHODS Healthy , sedentary women aged 50 - 70 years ( N=116 ) were r and omly assigned to a supervised 6-month swimming or walking program 3 sessions a week . They were further r and omised to usual care or a behavioural intervention . The same program was further continued unsupervised for 6 months . We assessed retention , adherence , stage of exercise behaviour and changes in fitness . RESULTS One hundred women ( 86 % ) completed 6 months and 86 ( 74 % ) continued for 12 months . Retention rates were similar for both exercise modes at 6 and 12 months . Adherence to swimming or walking was similar after 6 months ( 76.3 ( 95 % CI : 69.5 , 83.1)% vs. 74.3 ( 67.7 , 80.9)% ) and 12 months ( 65.8 ( 57.9 , 73.8)% vs. 62.2 ( 54.6 , 70.0)% ) . The behavioural intervention did not enhance retention or adherence . Fitness improved for both exercise modes after 6 months and was maintained at 12 months . CONCLUSIONS Either swimming or walking programs initiated with careful supervision over 6 months result ed in similar high retention and adherence rates by highly motivated older women over 12 months . Behavioural intervention in this setting did not improve these rates further OBJECTIVE The objective was to test , in a trial cohort of sedentary adults at risk of Type 2 diabetes , whether theory of planned behaviour ( TPB ) cognitions about becoming more physically active predicted objective and self-reported activity levels and change . DESIGN Participants of a r and omized controlled trial underwent measurement at baseline , 6 and 12 months . METHODS Participants ( N= 365 , 30 - 50 years ) were recruited via their parent or family history registers at 20 general practice s in the UK . Energy expenditure was measured objective ly at baseline and 1 year . Participants completed question naires assessing physical activity and beliefs about becoming more physically active over the next year at baseline , 6 and 12 months . RESULTS Between baseline and 12 months , objective energy expenditure in the cohort increased by an average of 20 minutes of brisk walking per day . Based on the 252 participants who provided complete data , affective attitude and perceived behavioural control consistently predicted intention , but intention and perceived behavioural control failed to predict physical activity levels or change ( p-values > .05 ) . CONCLUSIONS Failure of the theory to predict behaviour and behaviour change may be due to inapplicability of the theory to this at-risk population or to trial participation and intensive measurement facilitating behaviour change without affecting measured cognitions , or lack of correspondence between cognitive and behavioural measures . A wide range of potential personal and environmental mediators should be considered when design ing physical activity interventions among at-risk groups . High- quality experimental tests of the theory are needed in clinical population OBJECTIVES To evaluate a faith-based intervention ( Sisters in Motion ) intended to increase walking in older , sedentary African-American women . DESIGN R and omized controlled trial using within-church r and omization . SETTING Three Los Angeles churches . PARTICIPANTS Sixty-two African-American women aged 60 and older who reported being active less than 30 minutes three times per week and walked less than 35,000 steps per week as measured using a baseline pedometer reading . INTERVENTION Intervention participants received a multicomponent curriculum including scripture readings , prayer , goal - setting , a community re source guide , and walking competitions . Intervention and control participants both participated in physical activity sessions . MEASUREMENTS The primary outcome was change in weekly steps walked as measured using the pedometer . Secondary outcomes included change in systolic blood pressure ( SBP ) . Outcomes were assessed at baseline and 6 months after the intervention . RESULTS Eighty-five percent of participants attended at least six of eight sessions . Intervention participants averaged 12,727 steps per week at baseline , compared with 13,089 steps in controls . Mean baseline SBP was 156 mmHg for intervention participants and 147 mmHg for controls ( P=.10 ) . At 6 months , intervention participants had increased their weekly steps by 9,883 on average , compared with an increase of 2,426 for controls ( P=.02 ) ; SBP decreased on average by 12.5 mmHg in intervention participants and only 1.5 mmHg in controls ( P=.007 ) . CONCLUSION The Sisters in Motion intervention led to an increase in walking and a decrease in SBP at 6 months . This is the first r and omized controlled trial of a faith-based physical activity program to increase physical activity in older African-American women and represents an attractive approach to stimulate lifestyle change in this population BACKGROUND Declining physical activity is associated with a rising burden of global disease . Efforts to reverse this trend have not been successful . We aim ed to assess the efficacy of a facilitated behavioural intervention to increase the physical activity of sedentary individuals at familial risk of diabetes . METHODS We enrolled 365 sedentary adults who had a parental history of type 2 diabetes . They were recruited from either diabetes or family history registers at 20 general practice clinics in the UK . Eligible participants were r and omly assigned to one of two intervention groups , or to a comparison group . All participants were posted a brief advice leaflet . One intervention group was offered a 1-year behaviour-change programme , to be delivered by trained facilitators in participants ' homes , and the other the same programme by telephone . The programme was design ed to alter behavioural determinants , as defined by the theory of planned behaviour , and to teach behaviour-change strategies . The principal outcome at 1 year was daytime physical activity , which was objective ly measured as a ratio to resting energy expenditure . Analysis was by intention to treat . This study is registered as IS RCT N61323766 . FINDINGS Of 365 patients , we analysed primary endpoints for 321 ( 88 % ) for whom we had data after 1 year of follow-up . At 1 year , the physical-activity ratio of participants who received the intervention , by either delivery route , did not differ from the ratio in those who were given a brief advice leaflet . The mean difference in daytime physical-activity ratio , adjusted for baseline , was -0.04 ( 95 % CI -0.16 to 0.08 ) . The physical-activity ratio did not differ between participants who were delivered the intervention face-to-face or by telephone ( mean difference -0.05 ; 95 % CI -0.19 to 0.10 ) . INTERPRETATION A facilitated theory-based behavioural intervention was no more effective than an advice leaflet for promotion of physical activity in an at-risk group ; therefore health-care providers should remain cautious about commissioning behavioural programmes into individual preventive health-care services AIM To assess the cost-effectiveness of the ' Green Prescription ' physical activity counselling programme in general practice . METHOD Prospect i ve cost-effectiveness study undertaken as part of a cluster r and omised controlled trial with 12-month follow-up of 878 ' less-active ' patients aged 40 - 79 years in 42 general practice s in the Waikato . The intervention was verbal advice and a written exercise prescription given by general practitioners , with telephone exercise specialist follow-up compared with usual care . Main outcome measures included cost per total and leisure-time physical activity gain from health-funders ' and societal perspectives . RESULTS Significant increases in physical activity were found in the r and omised controlled trial . Programme-cost per patient was NZ170 dollars from a funder 's perspective . The monthly cost-effectiveness ratio for total energy expenditure achieved was 11 dollars per kcal/kg/day . The incremental cost of converting one additional ' sedentary ' adult to an ' active ' state over a twelve-month period was NZ1,756 dollars in programme costs . CONCLUSION Verbal and written physical activity advice given in general practice with telephone follow-up is an inexpensive way of increasing activity for sedentary people , and has the potential to have significant economic impact through reduction in cardiovascular and other morbidity and mortality OBJECTIVE To assess the cost-effectiveness of a primary care based intervention aim ed at increasing levels of physical activity in inactive people aged 45 - 74 . METHODS A total of 714 inactive people aged 45 - 74 , taken from two west London general practice s , were r and omised into two groups . Intervention subjects were invited to a consultation with an exercise development officer , and offered a personalised 10 week programme to increase their level of regular physical activity , combining leisure centre and home based activities . Control subjects were sent information on local leisure centres . All subjects were followed up at eight months . RESULTS There was a net 10.6 % ( 95 % confidence interval 4.5 to 16.9 % ) reduction in the proportion of people classified as sedentary in the intervention group compared with the control group , eight months after the intervention . The intervention group also reported an increase in the mean number of episodes of physical activity per week , as compared with the control group ( an additional 1.52 episodes ( 95 % confidence interval 1.14 to 1.95 ) ) . The cost of moving a person out of the sedentary group was shown to be less than 650 Pounds . The cost of moving someone to the now commonly recommended level was estimated at almost 2500 Pounds . CONCLUSIONS Moderate physical activity can be successfully encouraged in previously sedentary men and women aged 45 - 74 through a primary care based intervention . The process of recruitment was the most important variable cost . A high uptake rate would maximise cost-effectiveness , and sensitivity analysis suggests that unit costs could be halved with a more effective recruitment strategy BACKGROUND AND OBJECTIVE Assessing levels and determinants of physical activity as outcome measurements might have an independent effect on participant 's physical activity behavior . The objective is to study this effect in a r and omized controlled trial ( RCT ) promoting regular physical activity in Dutch general practice . METHODS Using a Solomon four-group design , participants were r and omized twice . After r and omization to a control or intervention-condition at general practice level ( N = 29 ) , participants were r and omized to a group participating in measurements at baseline , 2 and 6 months ( 3M-group , N = 361 ) , or a group only participating in measurements at 6 months ( 1M-group , N = 356 ) . Outcome measures assessed at 6 months included : level of physical activity ( self-reported and objective ly measured with accelerometry ) , meeting ACSM/CDC guideline for regular physical activity , stage of change , and determinants of physical activity . RESULTS Follow-up data on 635 participants ( 89 % ) was collected . Statistically significant measurement effects were found for meeting the ACSM/CDC guideline ( self-reported ) , self-efficacy for resisting relapse , knowledge , and on awareness . Other outcome measures showed positive trends , except stages of change . CONCLUSION Measurements of physical activity affect participant 's physical activity behavior , possibly triggered by a raised awareness about their own physical activity level . Implication s for future research are discussed , as well as method ologic limitations of the study design OBJECTIVE Older adults have low rates of physical activity participation , but respond positively to telephone-mediated support programs . Programs are often limited by reliance on professional staff . This study tested telephone-based physical activity advice delivered by professional staff versus trained volunteer peer mentors . DESIGN A 12-month , r and omized , controlled clinical trial was executed from 2003 - 2008 . Twelve volunteer peer mentors and 181 initially inactive adults ages 50 years and older were recruited from the San Francisco Bay Area . Participants were r and omized to : ( 1 ) telephone-based physical activity advice delivered by professional staff , ( 2 ) telephone-based physical activity advice delivered by trained volunteer peers , or ( 3 ) an attention-control arm of staff-delivered telephone support for nutrition . MAIN OUTCOME MEASURES Moderate-intensity or more vigorous physical activity ( MVPA ) was assessed at baseline , 6 , and 12 months with the Community Healthy Activities Model Program for Seniors ( CHAMPS ) Question naire , with accelerometry validation ( Actigraph ) in a r and omly selected sub sample . Treatment fidelity was examined through analysis of quantity and quality of intervention delivery . RESULTS At 6 and 12 months , both physical activity arms significantly increased MVPA relative to the control arm . Both physical activity arms were comparable in quantity of intervention delivery , but peers demonstrated more versatility and comprehensiveness in quality of intervention content . CONCLUSIONS This study demonstrates that trained peer volunteers can effectively promote physical activity increases through telephone-based advice . The results support a program delivery model with good dissemination potential for a variety of community setting BACKGROUND Over the last 10 years ' exercise referral schemes ' have been popular even though the evidence for effectiveness of any one-to-one intervention in primary care is deficient . We report the results of a primary care based one-to-one intervention that compared the effect of two communication styles with a no-intervention control group on self-reported physical activity at 12 months . METHODS In all , 1658 middle-aged men and women were r and omly assigned to 30 minutes of brief negotiation or direct advice in primary care or a no-intervention control group . The main outcome was self-reported physical activity at 12 months . Secondary outcome measures included change in blood pressure and body mass index . RESULTS Intention-to-treat analysis revealed no significant differences in physical activity between groups . Brief negotiation group participants who completed the study increased their physical activity significantly more than controls . There was no change in body mass index in any group . The brief negotiation group produced a greater reduction in diastolic blood pressure than direct advice . CONCLUSION If patients whose health may benefit from increased physical activity seek advice in primary care , 20 - 30 minutes of brief negotiation to increase physical activity is probably more effective than similar attempts to persuade or coerce . However , blanket physical activity promotion in primary care is not effective . The most effective way of increasing physical activity in primary care has yet to be determined The aim of this study was to compare short- ( 0 - 4 months ) and long-term ( 0 - 10 months ) effects of high-intensive Exercise on Prescription ( EoP ) intervention ( counseling and supervised exercise ) implemented in primary healthcare in a number of Danish counties with a low-intensive intervention ( counseling ) using maximal oxygen uptake ( VO(2max ) ) as the primary outcome . The study was conducted as a r and omized trial in 2005 - 2006 with a high and a low-intensive group . All the patients referred to the EoP scheme by their GP in the counties of Vejle and Ribe , Denmark , were eligible for the trial . The high-intensive EoP group received 4 months of group-based supervised training and attended five motivational counseling sessions . The low-intensive group only attended four motivational counseling sessions . Three hundred and twenty-seven patients entered the EoP scheme , and 52 ( 16 % ) volunteered for the r and omized trial . No short- or long-term differences were found between the high and the low-intensive groups for VO(2max ) ( short-term 95 % CI -1.1 ; 4.4 mL O(2)/(kg min ) , long-term 95 % CI -1.6 to 2.1 ) . The present study did not demonstrate any significant clinical outcome for the high-intensive EoP intervention as opposed to the low-intensive intervention OBJECTIVE The research tested the efficacy of planning and partner-based interventions to promote physical activity over six months . METHOD Local government ( council ) employees ( N = 257 ) were r and omly allocated to one of four conditions ( collaborative implementation intentions ; partner-only ; implementation intentions ; control group ) before completing measures at baseline and follow-ups at 1 , 3 and 6 months . Outcome measures comprised vali date d self-report measures of physical activity : the international physical activity question naire ( IPAQ ; Craig et al. , 2003 ) and self-report walking and exercise tables ( SWET ; Prestwich et al. , 2012 ) ; psychosocial mediators ( enjoyment , intention , self-efficacy , social influence ) ; weight and waist size ( baseline and 6 months only ) . RESULTS As well as losing the most weight , there was evidence that participants in the collaborative implementation-intention group were more physically active than each of the other three groups at 1- , 3- and 6-month follow-ups . Those in the implementation-intention and partner-only conditions did not outperform the control group on most measures . CONCLUSION Collaborative implementation intentions represent a potentially useful intervention to change important health behaviors that help reduce weight Voluntary employees ( N = 155 ) from nine different companies were screened by question naire for the study . They were r and omized into three study groups : counseling ( n = 52 ) , counseling + fitness testing ( n = 51 ) and control group ( n = 52 ) . The counseling was based on a goal -oriented conversation session for each participant and three follow-up appointments with an occupational nurse over a period of 1 year . The fitness tests were adapted from the UKK Health-related Fitness Test Battery . The outcome measures were the changes in the amount of leisure-time physical activity ( LTPA ) assessed by diary , pedometer and question naire at baseline and at 6 and 12 month follow-up visits . As a result , no statistically significant differences were detected between the three groups at either of the follow-up visits . It seemed , thus , that the two PA counseling methods implemented had no direct mid- or long-term effects on the LTPA of voluntary employees with no specific disease-related indication to increase LTPA OBJECTIVES To evaluate the long-term effects of a lifestyle intervention and a structured exercise intervention on physical fitness and cardiovascular risk factors in older adults . DESIGN Controlled trial with r and omization between the intervention groups . SETTING Belgium , Vlaams-Brabant . PARTICIPANTS One hundred eighty-six sedentary but healthy men and women aged 60 to 83 . INTERVENTIONS Participants in the lifestyle intervention were stimulated to integrate physical activity into their daily routines and received an individualized home-based program supported by telephone calls . The structured intervention consisted of three weekly supervised sessions in a fitness center . Both interventions lasted 11 months and focused on endurance , strength , flexibility , and postural and balance exercises . MEASUREMENTS Cardiorespiratory fitness , muscular strength , functional performance , blood pressure , and body composition were measured before ( pretest ) , at the end ( 11 months , posttest ) , and 1 year after the end ( 23 months , follow-up ) of the interventions . RESULTS The results from pretest to posttest have already been published . The current study analyzed the results from posttest to follow-up . There was a decrease in cardiorespiratory fitness , muscular fitness , and functional performance from posttest to follow-up in the structured intervention group but not in the control group or the lifestyle intervention group . At 23 months , participants in both groups still showed improvements in cardiorespiratory fitness . In addition , the structured group showed long-term improvements in muscular fitness , whereas the lifestyle group showed long-term improvements in functional performance . No long-term effects were found for blood pressure or body composition . CONCLUSION These results highlight the potential of a structured fitness center-based intervention and a home-based lifestyle intervention in the battle against inactivity in older adults . Lifestyle programs are especially valuable because they require fewer re sources and less time from health institutions and health practitioners Objective : This study investigated the role of coping plans and the use of selection , optimisation and compensation ( SOC ) strategies within an experimental evaluation of a 26-week physical exercise intervention . Methods : Older women ( N = 86 , M age = 73.7 years ) were r and omly assigned to a telephone-assisted or a self-administered coping planning intervention after 6 weeks ’ participation in an exercise programme . The number of different coping plans formulated , exercise-specific SOC strategy use and their interaction were used to predict objective ly measured long-term adherence to the intervention . Results : The number of coping plans formulated ( β = 0.28 ) and goal -pursuit strategies reported ( sum score of optimisation and compensation strategies , β = 0.39 ) predicted adherence to the exercise programme over 20 weeks . The predictive strength of coping plans increased with decreasing numbers of goal -pursuit strategies ( β = −0.21 ) . Women supported via telephone reported significantly more coping plans than did women in the self-administered coping planning group , F(1,80 ) = 9.47 , p = 0.003 . Conclusion : Coping plans have a buffering effect on adherence levels when use of SOC strategies is low . Older women 's adherence to physical activities may be improved if they are given direct support in generating coping plans involving strategies of selection , optimisation and compensation Aim To assess the cost-effectiveness of exercise on prescription with ongoing support in general practice . Methods Prospect i ve cost-effectiveness study undertaken as part of the 2-year Women 's lifestyle study r and omised controlled trial involving 1089 ‘ less-active ’ women aged 40–74 . The ‘ enhanced Green Prescription ’ intervention included written exercise prescription and brief advice from a primary care nurse , face-to-face follow-up at 6 months , and 9 months of telephone support . The primary outcome was incremental cost of moving one ‘ less-active ’ person into the ‘ active ’ category over 24 months . Direct costs of programme delivery were recorded . Other ( indirect ) costs covered in the analyses included participant costs of exercise , costs of primary and secondary healthcare utilisation , allied health therapies and time off work ( lost productivity ) . Cost – effectiveness ratios were calculated with and without including indirect costs . Results Follow-up rates were 93 % at 12 months and 89 % at 24 months . Significant improvements in physical activity were found at 12 and 24 months ( p<0.01 ) . The exercise programme cost was New Zeal and dollars ( NZ$ ) 93.68 ( € 45.90 ) per participant . There was no significant difference in indirect costs over the course of the trial between the two groups ( rate ratios : 0.99 ( 95 % CI 0.81 to 1.2 ) at 12 months and 1.01 ( 95 % CI 0.83 to 1.23 ) at 24 months , p=0.9 ) . Cost – effectiveness ratios using programme costs were NZ$687 ( € 331 ) per person made ‘ active ’ and sustained at 12 months and NZ$1407 ( € 678 ) per person made ‘ active ’ and sustained at 24 months . Conclusions This nurse-delivered programme with ongoing support is very cost-effective and compares favourably with other primary care and community-based physical activity interventions internationally OBJECTIVES To assess the long-term effectiveness of a telephone counseling intervention on physical activity and health-related quality of life in low-active older adults recruited through their primary care physician . DESIGN R and omized , controlled trial . SETTING Three primary care practice s from different socioeconomic regions of Auckl and , New Zeal and . PARTICIPANTS One hundred and eighty-six low-active adults ( aged 65 ) recruited from their primary care physicians ' patient data bases . INTERVENTION Eight telephone counseling sessions over 12 weeks based on increasing physical activity . Control patients received usual care . MEASUREMENTS Change in physical activity ( as measured using the Auckl and Heart Study Physical Activity Question naire ) and quality of life ( as measured using the Short Form-36 Health Survey ( SF-36 ) ) over a 12-month period . RESULTS Moderate leisure physical activity increased by 86.8 min/wk more in the intervention group than in the control group ( P=.007 ) . More participants in the intervention group reached 2.5 hours of moderate or vigorous leisure physical activity per week after 12 months ( 42 % vs 23 % , odds ratio=2.9 , 95 % confidence interval=1.33 - 6.32 , P=.007 ) . No differences on SF-36 measures were observed between the groups at 12 months . CONCLUSION Telephone-based physical activity counseling is effective at increasing physical activity over 12 months in previously low-active older adults This study investigated the effectiveness of a 10-week primary care exercise referral intervention on the physical self-perceptions of 40 - 70 year olds . Participants ( N=142 ) were assessed , r and omized to an exercise or control group , and reassessed at 16 and 37 weeks . The Physical Self-Perception Profile ( PSPP ; K. R. Fox , 1990 ) , fitness , physical activity , body mass index , body fat ( skinfolds ) , and hip and waist circumference were assessed . A multivariate analysis of variance revealed significant Group X Time interactions , with the exercise group showing greater physical self-worth , physical condition , and physical health at 16 and 37 weeks . Changes in all PSPP scales at baseline and 37 weeks were related to changes in anthropometric measures and adherence to the 10-week exercise program but not to changes in submaximal fitness parameters OBJECTIVE To evaluate the use of a local neighborhood environment-focused physical activity website and its effects on walking and overall physical activity in middle-aged adults . METHOD One-hundred and six ( 72 % women ) inactive adults aged 52+/-4.6 years were r and omly allocated to receive access to a neighborhood environment-focused website , ( Neighborhood group , n=52 ) or a motivational-information website ( Comparison group n=54 ) . Participants also received eleven emails over the 26 weeks . Study outcomes were objective ly-monitored website use , and self-reported total walking ( min/wk ) , total physical activity ( min/wk ) and neighborhood walking ( min/wk ) collected at baseline , 12 and 26 weeks . The study was conducted between August 2005 and February 2006 in Brisbane , Australia . RESULTS Website use was significantly greater among Neighborhood participants ( p=0.01 ) . Statistically significant increases in walking and total physical activity were observed in both groups . There was also a statistically significant interaction effect for total physical activity , with Neighborhood group participants maintaining more of their initial increase in physical activity at week-26 ( p<0.05 ) . Further , those in the Neighborhood group who used the website more often reported significantly more walking along the community trail at week-26 ( p=0.05 ) compared with those who did not . CONCLUSIONS A local neighborhood-environment focused physical activity website was more effective at engaging participants than a motivational-information website . Moreover , its use result ed in meaningful increases in physical activity relative to the comparison website To compare the effects of a pedometer-based behavioral intervention ( Fitness for Life [ FFL ] program ) and a traditional high-intensity fitness ( TRAD ) program on physical activity ( PA ) , Army Physical Fitness Test ( APFT ) , and coronary heart disease risk factors in Army National Guard members who failed the APFT 2-mile run . From a pool of 261 Army National Guard , a total of 156 were r and omized to TRAD or FFL for 24 weeks consisting of a 12-week progressive conditioning program followed by 12 weeks of maintenance . For both groups , the total APFT score and 2-mile run time/score improved from baseline to 12 weeks ( FFL : down 7.4 % , p = 0.03 ; TRAD : down 5 % , p = 0.08 ) but at 24 weeks they had regressed toward baseline . PA improved modestly and coronary risk profile changed minimally in both groups . A pedometer-based exercise intervention had results similar to a high-intensity program for improving PA , APFT , and 2-mile run times/score . Neither group sustained the improved run times over the 12 weeks of maintenance Primary care is a promising venue to build patient motivation and confidence to increase physical activity ( PA ) . Physician PA counselling has demonstrated some success ; however , maintenance of behaviour change appears to require more intensive interventions . In reality , most physicians do not have the necessary training nor the time for this type of counselling . The purpose of this paper is to outline the rationale , methods , and interventions for the ongoing physical activity counselling ( PAC ) r and omized controlled trial ( RCT ) , which aims to assess the impact of integrating a PA counsellor into a primary care practice . This RCT has 2 arms : ( i ) brief PA counselling ( 2 - 4 min ) from a health care provider and ( ii ) brief PA counselling+intensive PA counselling from a PA counsellor ( 3 months ) . The impact of this intervention is being evaluated using the comprehensive RE- AIM framework . One hundred twenty insufficiently active adult patients , aged 18 to 69 y and recruited during regular primary care visits have been r and omized . Dependent measures include psychological mediators , PA participation , quality of life , and physical and metabolic outcomes . The PAC project represents an innovative , theoretically-based approach to promoting PA in primary care , focusing on psychological mediators of change . We anticipate that key lessons from this study will be useful for shaping future public health interventions , theories , and research OBJECTIVE Given that only 25 % of Americans meet physical activity recommendations , there is a need to develop and disseminate effective , evidence -based interventions to promote physical activity . The authors tested 2 delivery channels , telephone and print , to determine whether one was more effective in promoting physical activity . DESIGN The authors r and omly assigned 239 healthy , sedentary adults to ( a ) telephone-based individualized feedback , ( b ) print-based individualized feedback , or ( c ) contact control . Both intervention arms were guided by a motivationally tailored , theoretically driven computer expert system . MAIN OUTCOME MEASURES Physical activity as measured by the 7-day Physical Activity Recall interview . RESULTS At 6 months , both telephone and print arms significantly increased in minutes of moderate intensity physical activity compared with control , with no differences between the intervention arms . At 12 months , print participants reported a significantly greater number of moderate intensity minutes than both telephone and control participants , who did not differ . CONCLUSION Results suggest that both telephone and print enhance the adoption of physical activity among sedentary adults ; however , print interventions may be particularly effective in maintaining physical activity in the longer term The objectives were to investigate in older adults ( 1 ) whether regular preventive home visits are associated with change or stability in physical activity and ( 2 ) whether education of home visitors influences stability and change in physical activity . The design was a prospect i ve controlled r and omised follow-up study with r and omization at municipality level ( 17 intervention and 17 control municipalities ) and outcomes measured at individual level . Visitors in the intervention-municipalities received regular education during 3 years . The effect of the intervention was measured by a question naire survey among 1,913 old persons living in the 34 municipalities at baseline and 4½-year follow-up . Changes in physical activity were measured through self-reported frequencies of vigorous physical activity . All logistic regression analyses were stratified by sex and age group ( 75 and 80 years old ) . There was no effect of receiving preventive home visits on change in physical activity among the men and among the 75-year-old women . Among the physically active 80-year-old women those who accepted and received more than four preventive home visits were more likely to go on being physically active compared to women who did not receive preventive home visits . Among the sedentary 80-year-old women those living in the intervention municipalities tended to increase their physical activity compared to the control women . These results were not seen in the old men . Preventive home visits as part of daily routine in primary care and education of home visitors and general practitioners may promote physical activity in older women BACKGROUND Faith-based interventions using a community-based participatory approach hold promise for eliminating ethnic health disparities . This study evaluated the effects of a volunteer-led statewide program to increase physical activity among members of African-American churches . METHODS African Method ist Episcopal churches within six regions ( Conferences ) were r and omly assigned to receive training in the program immediately or 1 year later . A cohort of 20 r and omly selected churches and 571 members within them took part in telephone surveys at baseline ( May-September 2003 ) and 1 year ( May-August 2004 ) and 2 years later ( June-September 2005 ) . Primary outcomes were physical activity participation , meeting physical activity recommendations , and stage of readiness for physical activity change . Statistical analyses were completed in April 2006 . RESULTS Volunteers ( N=889 ) from 303 churches were trained . Among survey respondents , physical activity did not increase significantly over time , although 67 % were aware of the program . Program awareness was significantly related to all three physical activity outcomes and to fruit and vegetable consumption . Pastoral support was significantly associated with physical activity . CONCLUSIONS Although this intervention reached a large number of churches and created awareness of intervention components , no effects on physical activity behaviors were found . Potential reasons for the lack of significant effects are discussed The health effects of increased physical activity in the prevention or treatment of any disease can only be meaningfully assessed if compliance to the exercise regimen is maintained . The current research examined compliance in a clinical trial investigating the effect of walking on bone loss in 229 postmenopausal women , r and omized into either a walking or a control group . Although at baseline there was no difference in physical activity between the two groups , after a period of 2 yr , the walking group reported significantly greater physical activity as measured by reported mean blocks walked daily and objective activity monitor day readings . Closer examination of the walking group revealed that compliers ( average 7 + miles walked/wk over the 2 yr ) , when compared to non-compliers , tended at baseline to be more active , lighter weight , and non-smokers . However , the variable that best differentiated between the two compliance groups was the frequency of reported illness over the 2-yr period , with compliers cl aim ing significantly less illness Background Web-based interventions are popular for promoting healthy lifestyles such as physical activity . However , little is known about user characteristics , adherence , attrition , and predictors of repeated participation on open access physical activity websites . Objective The focus of this study was Active-online , a Web-based individually tailored physical activity intervention . The aims were ( 1 ) to assess and compare user characteristics and adherence to the website ( a ) in the open access context over time from 2003 to 2009 , and ( b ) between trial participants and open access users ; and ( 2 ) to analyze attrition and predictors of repeated use among participants in a r and omized controlled trial compared with registered open access users . Methods Data routinely recorded in the Active-online user data base were used . Adherence was defined as : the number of pages viewed , the proportion of visits during which a tailored module was begun , the proportion of visits during which tailored feedback was received , and the time spent in the tailored modules . Adherence was analyzed according to six one-year periods ( 2003 - 2009 ) and according to the context ( trial or open access ) based on first visits and longest visits . Attrition and predictors of repeated participation were compared between trial participants and open access users . Results The number of recorded visits per year on Active-online decreased from 42,626 in 2003 - 2004 to 8343 in 2008 - 2009 ( each of six one-year time periods ran from April 23 to April 22 of the following year ) . The mean age of users was between 38.4 and 43.1 years in all time periods and both context s. The proportion of women increased from 49.5 % in 2003 - 2004 to 61.3 % in 2008 - 2009 ( P < .001 ) . There were differences but no consistent time trends in adherence to Active-online . The mean age of trial participants was 43.1 years , and 74.9 % were women . Comparing context s , adherence was highest for registered open access users . For open access users , adherence was similar during the first and the longest visits ; for trial participants , adherence was lower during the first visits and higher during the longest visits . Of registered open access users and trial participants , 25.8 % and 67.3 % respectively visited Active-online repeatedly ( P < .001 ) . Predictors of repeated use were male sex ( odds ratio [ OR ] = 1.2 , 95 % confidence interval [ CI ] = 1.04 - 1.38 ) and increasing age category in registered open access users , and age 46 - 60 versus < 30 years ( OR = 3.04 , 95 % CI = 1.25 - 7.38 ) and Swiss nationality ( ORnonSwiss= 0.64 , 95 % CI = 0.41 - 1.00 ) in trial participants . Despite reminder emails , attrition was much higher in registered open access users compared with trial participants , with a median lifetime website usage of 0 days in open access users and 290 days in trial participants . Conclusions Adherence , patterns of use , attrition , and repeated participation differed between trial participants and open access users . Reminder emails to encourage repeated participation were effective for trial participants but not for registered open access users . These issues are important when interpreting results of r and omized controlled effectiveness trials The aim of this study was to explore the feasibility of an exercise scientist ( ES ) working in general practice to promote physical activity ( PA ) to 55 to 70 year old adults . Participants were r and omised into one of three groups : either brief verbal and written advice from a general practitioner ( GP ) ( G1 , N=9 ) : or individualised counselling and follow-up telephone calls from an ES , either with ( G3 , N=8 ) or without a pedometer ( G2 , N=11 ) . PA levels were assessed at week 1 , after the 12-wk intervention and again at 24 weeks . After the 12-wk intervention , the average increase in PA was 116 ( SD=237 ) min/wk : N=28 , p<0.001 . Although there were no statistically significant between-group differences , the average increases in PA among G2 and G3 participants were 195 ( SD=207 ) and 138 ( SD=315 ) min/wk respectively , compared with no change ( 0.36 , SD=157 ) in G1 . After 24 weeks , average PA levels remained 56 ( SD=129 ) min/wk higher than in week 1 . The small numbers of participants in this feasibility study limit the power to detect significant differences between groups , but it would appear that individualised counselling and follow-up contact from an ES , with or without a pedometer , can result in substantial changes in PA levels . A larger study is now planned to confirm these findings OBJECTIVES To build upon state-of-the-art theory and empirical data to estimate the strength of multiple mediators of the efficacious Keep Active Minnesota ( KAM ) physical activity ( PA ) maintenance intervention . METHODS The total , direct , and indirect effects through which KAM helped r and omized participants ( KAM n = 523 ; UC n = 526 ) maintain moderate or vigorous PA ( MVPA ) for up to 2 years were estimated using structural equation modeling . RESULTS Multiple mediators explained half ( beta = .052 , P = .13 ) of the effect of KAM on MVPA ( beta = .105 , P = .004 ) . Self-efficacy was the upstream variable in 2 endogenously mediated effects , and the self-concept mediator emerged as the strongest predictor of MVPA . CONCLUSIONS KAM positively impacted self-efficacy , which was associated with PA enjoyment , integration into the self-concept , and PA maintenance . Successful long-term PA maintenance appears to be influenced by multiple small interrelated mediational pathways . Future research evaluating maintenance models should specify recursive relationships among mediators and outcomes BACKGROUND Given the low rates of physical activity participation , innovative intervention approaches are needed to make a public health impact . METHODS The study was conducted at the Miriam Hospital/Brown Medical School in Providence , RI , and in communities of Southeastern Massachusetts from 2002 to 2005 . Previously sedentary women ( n = 280 ; mean age = 47.1 ; 94.6 % Caucasian ) were r and omly assigned to one of three conditions : ( 1 ) Choose to Move , a self-help printed booklet ( n = 93 ) , ( 2 ) Jumpstart , a motivationally tailored , print based intervention ( n = 95 ) ; or ( 3 ) Wellness , women 's health material s ( n = 92 ) . Face-to-face contact at months 3 ( M3 ) and 12 ( M12 ) occurred within participants ' communities in local libraries . RESULTS At M3 , participants in the Jumpstart condition reported significantly more minutes of physical activity per week ( M = 140.4 , SE = 14.82 ) than participants in the Wellness condition ( M = 98.1 , SE = 15.09 ) , ( t(275 ) = 2.00 , p < 0.05 ) . The Jumpstart arm showed a trend towards significance ( t(275 ) = 1.93 , p = 0.054 ) when compared with the CTM arm ( M = 99.5 , SE = 15.11 ) ; there was no significant difference between the CTM and Wellness arms ( t(275 ) = 0.07 , p = NS ) . At M12 , there were no significant differences ( F(2,275 ) = 0.147 , p = NS ) between any of the treatment arms . CONCLUSIONS Results suggest that print-based programs for physical activity may be efficacious short-term , but more research is needed to find approaches that are effective long-term . It is possible to deliver print-based programs through existing community infrastructures , however these approaches need further evaluation to examine maintenance effects apart from the dem and characteristics of a research study Background The Active Plus project is a systematic ally developed theory- and evidence -based , computer-tailored intervention , which was found to be effective in changing physical activity behavior in people aged over 50 years . The process and effect outcomes of the first version of the Active Plus project were translated into an adapted intervention using the RE- AIM framework . The RE- AIM model is often used to evaluate the potential public health impact of an intervention and distinguishes five dimensions : reach , effectiveness , adoption , implementation , and maintenance . Objective To gain insight into the systematic translation of the first print-delivered version of the Active Plus project into an adapted ( Web-based ) follow-up project . The focus of this study was on the reach and effectiveness dimensions , since these dimensions are most influenced by the results from the original Active Plus project . Methods We optimized the potential reach and effect of the interventions by extending the delivery mode of the print-delivered intervention into an additional Web-based intervention . The interventions were adapted based on results of the process evaluation , analyses of effects within subgroups , and evaluation of the working mechanisms of the original intervention . We pretested the new intervention material s and the Web-based versions of the interventions . Subsequently , the new intervention conditions were implemented in a clustered r and omized controlled trial . Results Adaptations result ed in four improved tailoring interventions : ( 1 ) a basic print-delivered intervention , ( 2 ) a basic Web-based intervention , ( 3 ) a print-delivered intervention with an additional environmental component , and ( 4 ) a Web-based version with an additional environmental component . Pretest results with participants showed that all new intervention material s had modest usability and relatively high appreciation , and that filling in an online question naire and performing the online tasks was not problematic . We used the pretest results to improve the usability of the different interventions . Implementation of the new interventions in a clustered r and omized controlled trial showed that the print-delivered interventions had a higher response rate than the Web-based interventions . Participants of both low and high socioeconomic status were reached by both print-delivered and Web-based interventions . Conclusions Translation of the ( process ) evaluation of an effective intervention into an adapted intervention is challenging and rarely reported . We discuss several major lessons learned from our experience . Trial Registration Nederl and s Trial Register ( NTR ) : 2297 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2297 ( Archived by WebCite at http://www.webcitation.org/65TkwoESp ) Brief planning interventions , usually delivered within paper and pencil question naires , have been found to be effective in changing health behaviours . Using a double-blind r and omised controlled trial , this study examined the efficacy of two types of planning interventions ( action plans and coping plans ) in increasing physical activity levels when they are delivered via the internet . Following the completion of self-reported physical activity ( primary outcome ) and theory of planned behaviour ( TPB ) measures at baseline , students ( N = 1273 ) were r and omised into one of four conditions on the basis of a 2 ( received instructions to form action plans or not ) × 2 ( received instructions to form coping plans or not ) factorial design . Physical activity ( primary outcome ) and TPB measures were completed again at two-month follow-up . An objective measure ( attendance at the university 's sports facilities ) was employed 6 weeks after a follow-up for a duration of 13 weeks ( secondary outcome ) . The interventions did not change self-reported physical activity , attendance at campus sports facilities or TPB measures . This might be due to low adherence to the intervention protocol ( ranging from 58.8 to 76.7 % ) . The results of this study suggest that the planning interventions under investigation are ineffective in changing behaviour when delivered online to a sample of participants unaware of the allocation to different conditions . Possible moderators of the effectiveness of planning interventions in changing health behaviours are discussed OBJECTIVES To establish the effectiveness of the Green Prescription physical activity counseling program in increasing activity and quality of life in older community-dwelling people . DESIGN Post hoc subgroup analysis of a large cluster r and omized , controlled trial . SETTING One hundred seventeen doctors in 42 primary care practice s ( 74 % participation rate ) in the Waikato region of New Zeal and . PARTICIPANTS Two hundred seventy sedentary primary healthcare patients aged 65 and older ( 67 % participation rate ) . INTERVENTION Patients in intervention practice s prompted their primary care doctors or practice nurse to deliver brief activity counseling . A " Green Prescription " was written involving the negotiation of activity goals . Trained exercise specialists from a regional sports foundation gave follow-up telephone support over 3 months . MEASUREMENTS Leisure moderate and vigorous physical activity , total energy expenditure , systolic and diastolic blood pressure , health-related quality of life , musculoskeletal injuries , falls , and hospitalizations . RESULTS After 12 months of follow-up , leisure time moderate activity increased by 0.67 h/wk more in the intervention group than the control group ( 95 % confidence interval (CI)=0.17 - 1.17 ) and energy expenditure increased by 2.67 kcal/kg per week ( 95 % CI=0.87 - 4.47 ) more . For intervention group participants , vitality and general health scales of the 36-item Short Form showed statistically and clinical ly relevant improvements , and there was a decrease in hospitalizations ( P<.03 ) . There were no observable changes in blood pressure , injuries , or falls as a result of the Green Prescription program . CONCLUSION This physical activity intervention improved activity , energy expenditure , health-related quality of life , and hospitalizations for older primary care patients . Systematic inclusion of the Green Prescription in routine primary health care will probably lead to health gain for older people OBJECTIVE To examine the contribution of social-cognitive factors ( self-efficacy and affect ) in predicting long-term physical activity in a sample of older adults ( N=174 ) . DESIGN A prospect i ve design assessed physical activity and psychosocial variables at 2 and 5 years following a 6-month r and omized , controlled exercise trial . MAIN OUTCOME MEASURES The primary outcome variable was self-reported physical activity , with previous behavior , self-efficacy , and affect assessed as determinants of physical activity . RESULTS Covariance modeling analyses indicated that physical activity at Year 2 was the strongest predictor of physical activity at 5-year follow-up . Both self-efficacy and affect at Year 2 were also associated with physical activity at Year 5 , as was original treatment condition . Variables accounted for 35 % of the variance in Year 5 activity . CONCLUSION Older adults with higher levels of physical activity , more positive affect , and higher self-efficacy at Year 2 were more likely to continue to be active at Year 5 . This study is one of the longest follow-ups of exercise behavior in older adults and has implication s for structuring environments to maximize the maintenance of physical activity Background : Data regarding the effect of exercise programmes on older adults ’ health-related quality of life ( HRQOL ) and habitual physical activity are inconsistent . Objective : To determine whether a functional tasks exercise programme ( enhances functional capacity ) and a resistance exercise programme ( increases muscle strength ) have a different effect on the HRQOL and physical activity of community-dwelling older women . Methods : Ninety-eight women were r and omised to a functional tasks exercise programme ( function group ) , a resistance exercise programme ( resistance group ) , or normal activity group ( control group ) . Participants attended exercise classes three times a week for 12 weeks . The SF-36 Health Survey question naire and self-reported physical activity were obtained at baseline , directly after completion of the intervention ( 3 months ) , and 6 months later ( 9 months ) . Results : At 3 months , no difference in mean change in HRQOL and physical activity scores was seen between the groups , except for an increased SF-36 physical functioning score for the resistance group compared with the control group ( p = 0.019 ) and the function group ( p = 0.046 ) . Between 3 and 9 months , the self-reported physical functioning score of the function group decreased to below baseline ( p = 0.026 ) , and physical activity ( p = 0.040 ) decreased in the resistance group compared with the function group . Conclusions : Exercise has a limited effect on the HRQOL and self-reported physical activity of community-living older women . Our results suggest that in these subjects HRQOL measures may be affected by ceiling effects and response shift . Studies should include performance-based measures in addition to self-report HRQOL measures , to obtain a better underst and ing of the effect of exercise interventions in older adults PURPOSE To investigate the effectiveness of a peer-mentored exercise program , this study compared the program perception , retention and participation rates , and physical improvements of older adults trained by peer mentors ( PMs ) with those of a group trained by student mentors ( SMs ) . METHODS After a 30-week peer-mentor preparation , 60 older adults ( M + /- SD age : 68.7 + /- 6.1 yr ) were recruited and r and omly assigned to either the PM or the SM group . Both groups completed an identical 14-week fitness program . Pre- and posttraining assessment s of fitness were completed , and the efficacy of the PMs and SMs was surveyed . RESULTS High retention was observed in both groups , but the SM group had higher participation . Both groups improved their fitness significantly , with no significant posttest differences between the groups in most fitness measures or in program perception rates . DISCUSSION Findings suggest effectiveness of the peer-mentor model in an older adult exercise program OBJECTIVE To assess the effectiveness of a primary care referral scheme on increasing physical activity at 1 year from referral . Design Two-group r and omized controlled trial recruiting primary care referrals to a borough-based exercise scheme . Setting A local authority borough in the north-west of Engl and . Participants 545 patients defined as sedentary by a primary care practitioner . Intervention Referral to a local-authority exercise referral scheme and written information compared with written information only . Main outcome measures Meeting physical activity target at 12 months following referral , with a secondary outcome measured at 6 months from referral . RESULTS At 12 months , a non-significant increase of 5 per cent was observed in the intervention compared with control group , for participation in at least 90 minutes of moderate/vigorous activity per week ( 25.8 versus 20.4 per cent , OR 1.45 , 0.84 to 2.50 , p = 0.18 ) . At 6 months , a 10 per cent treatment effect was observed which was significant ( 22.6 versus 13.6 per cent , OR 1.67 , 1.08 to 2.60 , p = 0.05 ) . The intervention increased satisfaction with information but this did not influence adherence with physical activity . CONCLUSION Community-based physical activity referral schemes have some impact on reducing sedentary behaviour in the short-term , but which is unlikely to be sustained and lead to benefits in terms of health OBJECTIVES To describe activity patterns associated with a pedometer intervention in university freshmen and compare the intervention participants to controls for several health outcomes . METHODS Forty-six university freshmen were r and omized to a group that wore a pedometer across the academic year with a goal of 10,000 steps/day or to a control group . RESULTS Pedometer counts were highest initially but decreased over the academic year . December presented the fewest counts . There was little difference between groups in fitness or body composition . CONCLUSIONS Consideration of high-risk months and recommended steps/day may be important to effectively use pedometers to influence some health outcomes in university freshmen ABSTRACT A 6-month home-based ( HB ) physical activity program was compared to a control ( CTL ) condition in terms of effect on physical activity and health-related fitness in three generations of women ( daughter/mother/maternal gr and mother ) . Volunteers were r and omly assigned to a HB or CTL condition . HB participants ( n = 28 ) were asked to participate in lifestyle , aerobic , muscular strength , and flexibility activities at least 3 times per week and they completed 73 % of the recommended PA bouts . CTL condition participants ( n = 9 ) were asked to continue their usual pattern of physical activity . Changes in physical activity were measured pre- and post-intervention using the Physical Best question naire and pedometer step counts ( 3-day average ) . Changes in health-related fitness were assessed using Fitnessgram tests . Group × Time interactions were significant for changes in participation in flexibility activity ( d/wk ) and steps/day , indicating that the HB group experienced significant positive changes in the expected direction ( + 305 % and + 37 % , respectively ) , while the CTL group regressed ( −15 % and −13 % , respectively ) . The G × T interaction for mile time was significant , although not in the expected direction ( CTL group < by 14 % and HB group < by 5 % ) . Findings should be interpreted with caution due to several limitations of the study , but several suggestions are made for more effectively study ing this topic in the future Background : Both urban and rural adults are likely to be inactive , but rural adults have less access to exercise classes or facilities to increase physical activity . Objectives : To evaluate whether a telephone-only motivational interviewing ( MI ) intervention would increase daily physical activity of rural adults . Methods : This r and omized controlled trial enrolled 86 physically inactive adults living in rural communities ( mean age = 58 years , range = 30 - 81 years ) who stated that they were ready to increase physical activity during the next 6 months . Participants were assigned r and omly to MI intervention ( n = 43 ) or control ( n = 43 ) groups . The MI group participants received a pedometer and monthly MI telephone calls over 6 months from a counselor . Control group participants received an equal number of telephone calls without MI content . Physical activity was measured by self-report using the Community Healthy Activities Model Program For Seniors Physical Activity Question naire for Older Adults . Data were collected by mailed surveys and analyzed using analysis of variance . Results : Seventy-two participants completed the study ( 35 in the intervention group and 37 in the control group ) . The telephone-only MI intervention increased self-efficacy for exercise ( p = .019 ) but did not increase levels of physical activity ( p = .572 ) compared with controls . Discussion : The intervention increased self-efficacy for exercise but did not increase physical activity , possibly due to seasonal effects , the control condition , or the length of the MI intervention . Even so , future studies are warranted because telephone-only MI has potential as a practical , relatively inexpensive method to provide health counseling to rural adults in a broad geographic area . This study produced an effect size on physical activity that will be useful to guide future studies OBJECTIVE To increase walking activity in sedentary women . METHODS Women ( N = 253 ) were r and omly assigned to 1 of 3 groups : video education/control , brief telephone calls with no counseling , and telephone calls with counseling . Assessment s were made at baseline , 6 months , and 1 year . RESULTS All interventions increased the number of reported minutes walked and decreased the time to walk a mile . CONCLUSIONS The variability in the telephone counseling and brief telephone call groups seemed to suggest a group of participants who were high responders Despite the importance of self-care for dementia caregivers , few interventions have included a focus on health behaviors . This study reports outcomes of a telephone-based exercise intervention design ed for women caring for a spouse with dementia . Caregivers ( N = 137 ) were r and omized to intervention or control conditions . Participants with at- or below-median exercise scores at baseline had a significantly greater increase in exercise at 6-month follow-up compared with their control counterparts . At 6 months , participants had greater reductions in perceived stress relative to controls . Participants also reported significantly greater increases in exercise self-efficacy than caregivers in the control group at both follow-up points . Results indicate that spouse caregivers are able to increase their physical activity and that a focus on exercise in multicomponent interventions may be beneficial . Debate and discussion are needed to inform expectations for program effects and their maintenance and to explore the interface between enhanced self-care and caregiving perceptions OBJECTIVE --To determine the effectiveness of group- vs home-based exercise training of higher and lower intensities among healthy , sedentary older adults . DESIGN --Year-long r and omized , controlled trial comparing ( 1 ) higher-intensity group-based exercise training ; ( 2 ) higher-intensity home-based exercise training ; ( 3 ) lower-intensity home-based exercise training ; or ( 4 ) assessment -only control . SETTING --General community located in northern California . PARTICIPANTS --One hundred sixty women and 197 men 50 to 65 years of age who were sedentary and free of cardiovascular disease . One out of nine persons contacted through a community r and om-digit-dial telephone survey and citywide promotion were r and omized . INTERVENTIONS --For higher-intensity exercise training , three 40-minute endurance training sessions per week were prescribed at 73 % to 88 % of peak treadmill heart rate . For lower-intensity exercise training , five 30-minute endurance training sessions per week were prescribed at 60 % to 73 % of peak treadmill heart rate . MAIN OUTCOME MEASURES --Treadmill exercise test performance , exercise participation rates , and heart disease risk factors . RESULTS --Compared with controls , subjects in all three exercise training conditions showed significant improvements in treadmill exercise test performance at 6 and 12 months ( P less than .03 ) . Lower-intensity exercise training achieved changes comparable with those of higher-intensity exercise training . Twelve-month exercise adherence rates were better for the two home-based exercise training conditions relative to the group-based exercise training condition ( P less than .0005 ) . There were no significant training-induced changes in lipid levels , weight , or blood pressure . CONCLUSIONS --We conclude that ( 1 ) this community-based exercise training program improved fitness but not heart disease risk factors among sedentary , healthy older adults ; ( 2 ) home-based exercise was as effective as group exercise in producing these changes ; ( 3 ) lower-intensity exercise training was as effective as higher-intensity exercise training in the home setting ; and ( 4 ) the exercise programs were relatively safe BACKGROUND Project STRIDE is a 4-year r and omized controlled trial comparing two computer-based expert system guided intervention delivery channels ( phone vs. print ) for physical activity adoption and short-term maintenance among previously sedentary adults . METHODS Sedentary adults ( n=239 ) were r and omized to one of the following ( 1 ) telephone-based , individualized motivationally-tailored feedback ; ( 2 ) print-based , individualized motivationally-tailored feedback ; ( 3 ) contact-control delayed treatment group ( received intervention after 12 months as control ) . This paper : ( 1 ) outlines the study design , rationale , and participant sample ; and ( 2 ) describes relationships between baseline variables to better underst and their influence on the efficacy of the intervention . RESULTS Participants averaged 19.8+/-25.0 min of physical activity/week that was at least of moderate intensity , with no group differences . The average estimated VO(2 ) at 85 % of maximum heart rate was 25.6 ml/kg/min . Body fat was 34.1 % for women and 23.2 % for men and the BMI of the sample averaged 28.5 kg/m(2 ) . CONCLUSIONS Project STRIDE examines non face-to-face approaches for promoting physical activity behavior . It has unique features including a direct comparison of an expert system guided intervention delivered via phone or print . Future analyses will examine the cost-effectiveness of the interventions and this will likely yield important information for policy-makers Over two-thirds of Americans access the Internet and therefore , the Internet may be an important channel for reaching the large population of sedentary individuals . The purpose of this paper is to describe the methods for a r and omized controlled trial examining the efficacy of an Internet-based physical activity intervention relative to a print intervention that has been shown to be effective in previous trials . Specifically , 249 sedentary participants were r and omized to receive one of three interventions : 1 ) Internet-based motivationally-tailored individualized feedback ( Tailored Internet ) ; 2 ) print-based motivationally-tailored individualized feedback ( Tailored Print ) ; or 3 ) physical activity websites currently available to the public ( St and ard Internet ) . Participants completed the 7-Day Physical Activity Recall interview , wore an objective physical activity monitor ( i.e. , ActiGraph ) , and participated in a treadmill fitness test at baseline , 6 , and 12 months . The sample consisted of mostly women ( 84.2 % ) and Caucasian individuals ( 76.4 % ) who reported exercising an average of 21 min per week at baseline . This is the first study that we are aware of , that has examined the efficacy of a tailored Internet-based physical activity intervention . This study will have implication s for the dissemination of Internet-based physical activity interventions The purpose of this study was to test the feasibility of the WALC intervention ( Walk ; Address pain , fear , fatigue during exercise ; Learn about exercise ; Cue by self-modeling ) , and determine its effects on self-efficacy and outcome expectations , exercise activity and free living activity , physical and mental health status , and falls and fall-related injuries . A total of 17 sedentary older women with a mean age of 88 + /- 3.7 years were r and omly assigned to receive either the WALC intervention or routine care . Ninety percent of those in the treatment group initiated and engaged in a regular exercise program during the 6 months of the study . There was a statistically significant difference in self-efficacy expectations , exercise behavior , and overall activity between the two groups . Those in the treatment group had stronger self-efficacy expectations related to exercise ; engaged in more exercise and more free living activity ; and although not statistically significant , had stronger outcome expectations following exposure to the WALC intervention when compared with those who received routine care . To help older adults initiate and adhere to an exercise program , nurses can easily implement the WALC intervention in a variety of setting OBJECTIVES This study examined the health-related effects of two worksite interventions , physical exercise and reduced workhours , on women employed in dentistry . METHODS Six workplaces were r and omized to one of the following three conditions : ( i ) 2.5 hours of weekly , m and atory physical exercise of middle-to-high intensity to be performed during workhours ( N=62 ) , ( ii ) a reduction of full-time weekly workhours from 40 to 37.5 hours ( N=50 ) , and ( iii ) reference . In all , 177 women participated . Biomarkers and self-ratings in question naires were obtained before the intervention ( T ( 1 ) ) , and six ( T ( 2 ) ) and 12 months ( T ( 3 ) ) after the intervention . RESULTS The results showed increased levels of physical activity and exercise in all of the groups , the level of physical exercise being significantly greater in the physical exercise group . Repeated- measures analyses of variance using data from T ( 1 ) and T (3)for biological measures and all three time points for self-ratings produced significant interaction effects for glucose , waist-to-hip ratio , and work ability and clear trends for general symptoms and upper-extremity disorders . Posthoc analyses showed that the results of the health-related measures differed between the interventions , decreased glucose and upper-extremity disorders in the exercise group , and increased high-density lipoprotein and waist-to-hip ratio among those working reduced hours . CONCLUSIONS These results show that the two interventions had small and varied effects on biomarkers and self-reports of different aspects of health among women . It is suggested that interventions involving a modest reduction in workhours seem to be more effective if these hours are used for physical exercise The effects of one year of exercise training on cardiorespiratory fitness , levels of daily leisure activity , and blood lipids ( cholesterol and high density lipoproteins ) were studied in a prospect i ve , r and omized clinical trial . Two hundred and twenty-four men aged 55 to 65 years volunteered for the study and were r and omly allocated to a control ( n = 111 ) or an activity ( n = 113 ) group with stratification on blue or white collar job classification . After the attrition due to loss to follow-up , 100 men remained in each of the control and activity groups . The exercising men met an average of 2.5 times per week over the year and their VO2 max or peak VO2 ( ml X kg-1 X min-1 ) increased significantly ( p = .001 , 11 % ) compared with controls . There were no significant changes in maximal heart rate ( 155 bpm ) and respiratory exchange ratio ( 1.1 ) , although ventilation ( 80 to 90 l X min-1 ) increased significantly in the trained group . In addition , the VO2 at a heart rate of 125 bpm increased significantly ( p less than .001 ) in the trained group ( 14.7 % ) over that observed in the control ( 1.9 % ) . There were no significant differences between the groups with respect to the remaining end-points To assess the effectiveness of physician prescribed exercise , health education , and patient self-monitoring , 124 firefighters were medically screened and r and omly allocated to a control and two treatment groups . Physiologic and reporting methods were employed to assess adherence to regular exercise at three months and six months after the initial exercise prescription . Addition of a health education program significantly improved compliance over that achieved by a physician consultation . Self-monitoring did not produce a further increase in compliance . Improvement in the treatment groups was limited to three months after prescription ; at six months , the treatment and control population s had similar exercise patterns BACKGROUND Regular physical activity reduces the risk for chronic diseases among older adults . Older adults are likely to be seen by primary care clinicians who can play a role in promoting physical activity among their patients . DESIGN In this r and omized controlled trial ( 1998 - 2003 ; data analyzed 2004 - 2005 ) , we compared the effects of brief advice to exercise from a clinician supplemented by telephone-based counseling by health educators ( extended advice ) to brief advice from a clinician alone ( brief advice ) . SETTING / PARTICIPANTS A total of 100 primary care patients ( 63.2 % female , 14.7 % minority , mean age=68.5 years ) participated in the trial . INTERVENTIONS The extended-advice intervention consisted of clinician advice plus exercise counseling via telephone provided by research staff , and the brief advice condition consisted of clinician advice alone . Both interventions focused on promoting moderate-intensity physical activity . MAIN OUTCOME MEASURES Self-reported physical activity using the 7-Day Physical Activity Recall instrument and objective activity monitoring using Biotrainers were assessed at baseline , and at 3 and 6 months . RESULTS Participants in the extended-advice arm reported significantly greater participation in moderate-intensity physical activity than the brief-advice group at 3 months ( + 57.69 minutes vs 12.45 minutes ; 3.84 kcal/week vs 0.83 kcal/week ) and 6 months ( + 62.84 minutes vs 16.60 minutes ; 4.19 kcal/week vs 1.1 kcal/week ) . Objective activity monitoring also showed significantly increased physical activity among extended-advice versus brief-advice participants at both time points ( + 50.79 vs -11.11 ; + 42.39 vs -24.18 , respectively ) . CONCLUSIONS These data indicate that clinician advice with follow-up counseling can promote adoption of moderate-intensity physical activity among older , primary care patients To investigate the applicability and effectiveness of a peer-mentored exercise program , this study compared the retention and participation rates , and physical improvements of older adults trained by peer mentors ( PM ) to a group trained by young qualified student mentors ( SM ) . A group of older adults were prepared as peer mentors through a 30-week preparation program . Later , 60 older adults ( mean ± SD age : 68.7 ± 6.1 years ) were recruited and r and omly assigned to either the PM or SM group . Both groups completed an identical 35-week fitness program . Pre- , midterm- and post-training assessment s of fitness were completed and rates of participation and retention were documented . The same retention rates were observed in the two groups , but SM group had higher participation . Both groups improved significantly in all measures of fitness and there were no significant post-test differences between the groups in the fitness measures . Findings suggest that the peer mentor model is applicable in an older adult exercise program and may be as effective as a program mentored by young professionals Sixty-four male and female sedentary employees were r and omly assigned to an intervention group or control group to determine the effects of behavioral skill training on adoption and maintenance of exercise . Both received a 9-month membership at a local fitness facility . The control group received a 12-week semistructured course , which included a facility orientation and three meetings with a personal trainer . The intervention group received a 12-week behavioral skills course and were encouraged to participate in a 12-week semistructured exercise course followed by a 3-month problem-solving support intervention . Both groups improved their daily energy expenditure , the amount of moderate and vigorous activity they performed , and their strength and flexibility . The study sample was too small to show substantial differences between the intervention and control group . Changes in mediator variables were mixed Purpose . To compare the effects of stage-matched and st and ard print material s for physical activity ( PA ) change . Design . Participants were r and omized into ( 1 ) a stage-matched intervention group ( n = 165 ) , ( 2 ) a st and ard intervention group ( n = 176 ) , or ( 3 ) a no-contact control group ( n = 166 ) . The stage-matched and st and ard intervention groups both received material s at baseline , 3 months , and 6 months . Assessment s of all three groups were conducted at baseline , 6 , and 12 months . Setting . Canadian worksites . Subjects . Employees ( N = 507 ) . Interventions . Five motivationally targeted booklets were developed for the stage-matched group . The st and ard group received Canada 's Physical Activity Guide and h and book . Measures . The main dependent variable was PA , expressed as metabolic equivalent ( MET ) minutes and measured using the Godin Leisure-Time Exercise Question naire . Demographic characteristics and stages of change for PA were also assessed . Results . At 12 months mean weekly MET minutes for combined moderate and vigorous activity increased from baseline by 223 , 67 , and 78 for the stage-matched , st and ard , and control groups , respectively ; however , differences were not significant ( p > .05 ) . Women in the stage-matched group over the 12-month period significantly increased their activity by 327 weekly MET minutes whereas the st and ard and control groups declined their activity ( F = 3.01 , p < .05 ) . Conclusion . PA stage-matched material s delivered in the workplace are efficacious for women but not men . Future interventions should explore the use of these intervention material s in conjunction with multilevel strategies , and particular attention should be paid to possible gender differences |
12,457 | 30,185,545 | After a median follow-up of 10 years , there was no significant difference in prostate cancer-specific mortality in men receiving care by general practice s r and omised to a single PSA screening intervention compared with men receiving care … RETURN TO | null | null |
12,458 | 23,032,675 | RESULTS Overall , both education and contact had positive effects on reducing stigma for adults and adolescents with a mental illness .
However , contact was better than education at reducing stigma for adults .
For adolescents , the opposite pattern was found : education was more effective .
Overall , face-to-face contact was more effective than contact by video . | OBJECTIVE Public stigma and discrimination have pernicious effects on the lives of people with serious mental illnesses .
Given a plethora of research on changing the stigma of mental illness , this article reports on a meta- analysis that examined the effects of antistigma approaches that included protest or social activism , education of the public , and contact with persons with mental illness . | This study examined how two types of public education programs influenced how the public perceived persons with mental illness , their potential for violence , and the stigma of mental illness . A total of 161 participants were r and omly assigned to one of three programs : one that aim ed to combat stigma , one that highlighted the association between violence and psychiatric disorders , and a control group . Participants who completed the education-about-violence program were significantly more likely to report attitudes related to fear and dangerousness , to endorse services that coerced persons into treatment and treated them in segregated areas , to avoid persons with mental illness in social situations , and to be reluctant to help persons with mental illness Due to the prevalence and serious consequences associated with mental illness stigma , a number of educational interventions have been developed to decrease stigma . One potential intervention is administering brief simulations of auditory hallucinations , but no empirical evaluations have been published . This research examined the efficacy of a brief simulation on stigma across two listening conditions . After completing a stigma measure , participants ( N = 127 ) listened to a simulation and were r and omly assigned to one of two listening conditions : ( 1 ) sitting in a research lab , or ( 2 ) ambulating around a college campus completing two tasks . All participants then completed the stigma measure a second time . Regardless of listening condition , the simulations led to changes on two aspects of stigma — less willingness to help/interact and stronger attitudes for forcing treatment on those with mental illness . These findings suggest that brief simulations require additional careful evaluation of their efficacy prior to wide implementation Acceptance and commitment therapy ( ACT ) has previously been shown to alter stigmatizing attitudes and to be relatively useful for psychologically inflexible participants . The present study is the first to bring those two findings together by comparing ACT to an education intervention for reducing stigma toward people with psychological disorders , and examining whether results differ for psychologically inflexible versus flexible individuals . A sample of college students ( N = 95 ) was r and omly assigned to a 2(1)2h ACT or educational workshop . Measures were taken before and after the workshop and at a 1-month follow-up . ACT reduced mental health stigma significantly regardless of participants ' pre-treatment levels of psychological flexibility , but education reduced stigma only among participants who were relatively flexible and non-avoidant to begin with . Acceptance could be an important avenue of exploration for stigma research ers PURPOSE This study examined the effectiveness of an intervention to reduce explicit and implicit stigma-relevant attitudes toward mental illness and treatment-seeking and behavioural indicators of willingness to seek treatment . METHODS Adolescents were r and omly assigned to the experimental ( education about mental illness and treatment involving psychoeducation and contact ( via DVD ) with an affected individual ) or control intervention ( education about tobacco ) . RESULTS Findings suggest the stigma intervention was effective at reducing explicit but not implicit stigma-relevant attitudes . As hypothesized , participants receiving the experimental intervention reported less explicit stigma toward treatment and greater openness to personally seek treatment if they had also reported prior mental health treatment . CONCLUSIONS AND IMPLICATION S These findings support the potential for a brief educational intervention among adolescents to reduce negative attitudes toward mental health treatment , but raise questions about how to effectively address implicit stigma as well as the importance of translating stigma reduction into behavior changes Stigma reduction programs are dominated by a biomedical model that presents depression as a medical illness . Alternately , a context ual model emphasizes that one should not be blamed for environmental influences . This study compared biomedical , context ual , and control stigma reduction programs to each other and to a no-program control . The main hypotheses were that the context ual program would have the greatest impact and that a match between participants ’ beliefs about depression and the model presented would moderate this effect . Seventy-four participants were r and omized to the 3 programs and 12 participants served as a no-program control . The context ual and control programs reduced stigma significantly compared with the no-program control , whereas the biomedical program did not . Beliefs about depression moderated this effect only for the biomedical condition . Context ual and control programs seem to be effective but a biomedical model may be risky for those who disagree with the model . Theoretical implication s are discussed OBJECTIVE This study evaluated a consumer delivered anti-stigma presentation , In Our Own Voice ( IOOV ) , with Masters of Social Work ( MSW ) students , replicating a previous study with undergraduates . METHODS Thirty MSW students completed pre and post surveys to measure changes in attitude , knowledge and social distance after the presentation . RESULTS Paired sample s t-tests showed increases in attitude ( p < .001 ) , knowledge ( p < .05 ) , and social distance ( p < .001 ) . Compared with previous research on undergraduate students , MSW students scored higher on all three pre-test measures ( all p < .001 ) . CONCLUSIONS The results further support the effectiveness of IOOV and indicate that graduate level helping professionals can benefit from anti-stigma programs . Future research should go beyond self-report knowledge and attitude evaluation , test the efficacy of the components of the IOOV program ( video , contact with presenters ) , and test the lasting effects of the program ABSTRACT This study examines the impact of two versions of anti-stigma programs — education and contact — presented on videotape . A total of 244 people were r and omly assigned to education or contact conditions and completed pre-test , post-test , and follow-up measures of stereotypes . Results suggest that the education videotape had limited effects , mostly showing improvement in responsibility ( people with mental illness are not to blame for their symptoms and disabilities ) . Watching the contact videotaped showed significant improvement in pity , empowerment , coercion , and segregation . Contact effects were evident at post-test and 1 week follow-up . Implication s of these findings for future research are discussed OBJECTIVE We design ed our study to assess if computer-assisted anti-stigma interventions can be effective in reducing the level of psychiatric stigma in a sample of special education university students . METHODS We enrolled 193 graduate students . They had two study visits with an interval of 6 months . The participants were r and omly distributed into three study groups : 76 students read anti-stigma printed material s ( reading group , RG ) , and 69 studied an anti-stigma computer program ( program group , PG ) , and 48 students were in a control group ( CG ) and received no intervention . We used the Bogardus scale of social distance ( BSSD ) , the community attitudes toward the mentally ill ( CAMI ) question naire , and the psychiatric knowledge survey ( PKS ) as the main outcome measures . RESULTS After the intervention BSSD , CAMI and PKS scores significantly improved both in RG and PG . After 6 months in RG two out of three CAMI subscales and PKS scores were not different from the baseline . In PG all stigma and knowledge changes remained significant . CONCLUSIONS This study demonstrated that computers can be an effective mean in changing attitudes of students toward psychiatric patients . PRACTICE IMPLICATION S A computer-mediated intervention has the potential for educating graduate students about mental disease and for reducing psychiatric stigma BACKGROUND Little is known about the efficacy of educational interventions for reducing the stigma associated with depression . AIMS To investigate the effects on stigma of two internet depression sites . METHOD A sample of 525 individuals with elevated scores on a depression assessment scale were r and omly allocated to a depression information website ( BluePages ) , a cognitive-behavioural skills training website ( MoodGYM ) or an attention control condition . Personal stigma ( personal stigmatising attitudes to depression ) and perceived stigma ( perception of what most other people believe ) were assessed before and after the intervention . RESULTS Relative to the control , the internet sites significantly reduced personal stigma , although the effects were small . BluePages had no effect on perceived stigma and MoodGYM was associated with an increase in perceived stigma relative to the control . Changes in stigma were not mediated by changes in depression , depression literacy or cognitive-behavioural therapy literacy . CONCLUSIONS The internet warrants further investigation as a means of delivering stigma reduction programmes for depression This study examines the effects of Entertainment-Education strategy on knowledge acquisition about schizophrenia and stigma reduction , using pretest posttest control group and 2 X 3 ( advocate 's perspective X message style ) between-subjects factorial design . Participants watched an accurate and empathetic movie portrayal of schizophrenia , followed by an educational trailer . Participants ( N= 165 ) were r and omly assigned to one of eight conditions ( six manipulated conditions , control , a group who watched a trailer prior to the movie ) . Results showed that viewing an accurate and empathetic movie portrayal increased knowledge . The educational trailer increased not only knowledge acquisition but influenced stigma reduction . Structural equation modeling analysis revealed that entertainment and educational value of the movie mediated stigma reduction . Implication s of this study to the mental health research and the design of Entertainment-Education contents are discussed Rreliminary evidence suggests that mental health consumers can successfully serve as peer companions , case management aides , case managers , job coaches , and drop-in center staff . However , few empirical investigations have addressed the use of consumers to train mental health professionals . This project employed a r and omized design to test the effects of using consumers as trainers for mental health service providers . Fifty-seven state mental health professionals participated in a two-day training design ed to acquaint trainees with the attitudes and knowledge necessary for delivering assertive case management services . Participants were r and omly assigned to one of two conditions : one in which they received the second day of training from a consumer and the other involving training by a nonconsumer . Analyses revealed that post-training attitudes were significantly more positive for those participants trained by the consumer . Subjective evaluations also reflected positive reactions to the use of consumers as trainers . Implication s for further use of mental health consumers as trainers are explored The effects of stereotype suppression on psychiatric stigma were investigated in two studies . In experiment 1 , 52 participants were presented with a photograph of someone labeled with schizophrenia and instructed to write a passage describing a day in that person 's life . Half of the participants were instructed to avoid using schizophrenia-related stereotypes in their passages ( the stereotype suppression condition ) . Participants were then presented with a photograph of a different individual labeled with schizophrenia and asked to write another passage with stereotype suppression instructions omitted . The results showed that while stereotype suppression occurred for the first passage , the expected rebound effects were not observed in the second passage . Furthermore , the results were unchanged when participants ' prior experience with persons with mental illness was considered . In a second study , the effects of stereotype suppression on behavior ( i.e. seating distance from a person with schizophrenia ) were examined in 58 participants . While the stereotype suppression instructions result ed in less stereotypical passages , replicating the results of study 1 , no rebound effects on behavior were observed . A non-significant trend was observed whereby previous contact with persons with mental illness was associated with less social distance from someone with schizophrenia . Implication s of the findings for reducing psychiatric stigma are discussed BACKGROUND Education is integral to reducing stigma toward the mentally ill . Medical educators have a key role in delivering education that reduces that stigma . Undergraduate psychiatric training and specific education programs are both effective in reducing stigma . However , many students are exposed to concepts of mental illness at a much earlier stage in their education . No previous study has explored the effect of intervention such as role-play on student attitudinal development . OBJECTIVES This study 's objective was to identify whether undergraduate role-play exercises featuring mental illness influenced development of attitudes toward the mentally ill . METHODS A r and omized controlled trial was used to compare attitudinal scores between students exposed to a mental illness role-play as part of routine teaching and a control group that did not receive the teaching . RESULTS A total of 332 students provided data . There were no between-group differences for any attitudinal scores , although gender ( being female ) and experience of mental illness were associated with more positive attitudinal scores . CONCLUSIONS Single high-intensity routine teaching sessions such as role-play involving metal illness do not influence student attitudes Trauma risk management ( TRiM ) is an intensive posttraumatic stress disorder ( PTSD ) psychoeducational management strategy based on peer-group risk assessment developed by the UK Royal Navy ( RN ) . TRiM seeks to modify attitudes about PTSD , stress , and help-seeking and trains military personnel to identify at-risk individuals and refer them for early intervention . This quasiexperimental study found that TRiM training significantly improved attitudes about PTSD , stress , and help-seeking from TRiM-trained personnel . There was a nonsignificant effect on attitudes to seeking help from normal military support networks and on general health . Within both the military and civilian population s , stigma is a serious issue preventing help-seeking and reducing quality of life . The results suggest that TRiM is a promising antistigma program within organizational setting Mental illness stigma is quite prevalent with dire consequences . A number of interventions to decrease stigma have been formulated , but have variable effectiveness and limited dissemination . This research examined the impact of two brief interventions : a film depicting individuals with schizophrenia ( filmed contact ) and a simulation of auditory hallucinations . Participants ( N = 143 ) were r and omly assigned to one of three interventions : ( 1 ) filmed contact , ( 2 ) simulation , or ( 3 ) no intervention , and completed two stigma measures prior to , immediately after , and 1 week after the intervention . The filmed contact intervention led to decreases in stigma which persisted across 1 week . However , the simulation led to increases in stigma . The results suggest that a filmed contact intervention may decrease two aspects of mental illness stigma ( social distance and negative emotions ) , which has implication s for wide dissemination . The efficacy of a hallucination simulations intervention remains dubious OBJECTIVE This study was design ed to investigate the efficacy of a web-based mental disorder stigma education program for mental health professionals . METHODS The sample consisted of 205 individuals who were either residents or specialists in psychiatry . Participants were contacted through a national web-based e-mail group that consisted of professionals in psychiatry , who were r and omly assigned to experimental and control groups . The experimental group received an informative e-mail which contained a general account of " stigma " before they were asked to respond to an Internet-based question naire which was design ed to predict their stigmatizing attitudes towards individuals with mental disorders . Control subjects , on the other h and , were asked to respond to the same Internet-based question naire without having been given the aforementioned informative e-mail . RESULTS The experimental group , compared to the control group , demonstrated a lesser stigmatizing attitude towards individuals with mental illness , as measured by the Internet-based survey which utilized the " social distance " concepts of stigma . CONCLUSIONS These data suggest that such " anti-stigma " campaigns using the potential of the Internet might be an effective tool in the fight against the stigmatization of persons with mental illness The effects of three strategies for changing stigmatizing attitudes -- education ( which replaces myths about mental illness with accurate conceptions ) , contact ( which challenges public attitudes about mental illness through direct interactions with persons who have these disorders ) , and protest ( which seeks to suppress stigmatizing attitudes about mental illness)--were examined on attributions about schizophrenia and other severe mental illnesses . One hundred and fifty-two students at a community college were r and omly assigned to one of the three strategies or a control condition . They completed a question naire about attributions toward six groups -- depression , psychosis , cocaine addiction , mental retardation , cancer , and AIDS -- prior to and after completing the assigned condition . As expected , results showed that education had no effect on attributions about physical disabilities but led to improved attributions in all four psychiatric groups . Contact produced positive changes that exceeded education effects in attributions about targeted psychiatric disabilities : depression and psychosis . Protest yielded no significant changes in attributions about any group . This study also examined the effects of these strategies on processing information about mental illness |
12,459 | 20,393,950 | Historical and programme documentation has clearly established the impact of IRS .
However , the number of high- quality trials are too few to quantify the size of effect in different transmission setting s. The evidence from r and omized comparisons of IRS versus no IRS confirms that IRS reduces malaria incidence in unstable malaria setting s , but r and omized trial data from stable malaria setting s is very limited . | BACKGROUND Primary malaria prevention on a large scale depends on two vector control interventions : indoor residual spraying ( IRS ) and insecticide-treated mosquito nets ( ITNs ) .
Historically , IRS has reduced malaria transmission in many setting s in the world , but the health effects of IRS have never been properly quantified .
This is important , and will help compare IRS with other vector control interventions .
OBJECTIVES To quantify the impact of IRS alone , and to compare the relative impacts of IRS and ITNs , on key malariological parameters . | Background Anaemic status is determined by haemoglobin using the HemoCue system or haematocrit measurements , and a threefold conversion is commonly used to equate the two measures ( haemoglobin = haematocrit/3 ) . The validity of this conversion in malaria endemic setting s was assessed . Methods Concurrent measures of haemoglobin and centrifuged haematocrit in children aged 6–59 months were compared by modelling the difference between the two measures against their average . A r and om effects linear regression of the difference of the measures on their average was used to describe the line of best agreement and 95 % limits of agreement for these two measures over a range of values after adjusting for statistically significant covariates . Results There was a consistent bias between the two measures , with haemoglobin less than haematocrit/3 in 87 % ( 899/1,030 ) of observations . This difference was non-uniform , decreasing with the average measure , i.e. less difference at higher haemoglobin and haematocrit values . In these studies , use of haematocrit would have underestimated the prevalence of anaemia by misclassifying 10 % ( 89/920 ) of individuals with haemoglobin < 11 g/dl , 66 % ( 252/380 ) of individuals with haemoglobin < 8 g/dl and 100 % ( 23/23 ) of individuals with haemoglobin < 5 g/dl . The mean difference between the measures was greater in males than females , increased with age between 6–59 months , and was greater in the wet than dry season suggesting that the relationship between haemoglobin and haematocrit may be modified by exposure to malaria . Conclusion The regression model indicated that the st and ard threefold conversion from haematocrit to haemoglobin underestimates the prevalence of haemoglobin < 11 g/dl in children under five years of age in malaria endemic setting s. This bias was more acute for more severe anaemia defined by haemoglobin < 8 g/dl and haemoglobin < 5 g/dl . This has important implication s for the comparability of studies using these different measures . Direct determination of haemoglobin should be the measurement of choice for assessing anaemia outcomes in malaria intervention trials and surveys BACKGROUND The published literature on cluster r and omized trials focuses on outcomes that are either continuous or binary . In many trials , the outcome is an incidence rate , such as mortality , based on person-years data . In this paper we review methods for the analysis of such data in cluster r and omized trials and present some simple approaches . METHODS We discuss the choice of the measure of intervention effect and present methods for confidence interval estimation and hypothesis testing which are conceptually simple and easy to perform using st and ard statistical software . The method proposed for hypothesis testing applies a t-test to cluster observations . To control confounding , a Poisson regression model is fitted to the data incorporating all covariates except intervention status , and the analysis is carried out on the residuals from this model . The methods are presented for unpaired data , and extensions to paired or stratified clusters are outlined . RESULTS The methods are evaluated by simulation and illustrated by application to data from a trial of the effect of insecticide-impregnated bednets on child mortality . CONCLUSIONS The techniques provide a straightforward approach to the analysis of incidence rates in cluster r and omized trials . Both the unadjusted analysis and the analysis adjusting for confounders are shown to be robust , even for very small numbers of clusters , in situations that are likely to arise in r and omized trials A project testing the efficacy of insecticide (permethrin)-impregnated bed nets , compared with impregnated door and window curtains , residual house spraying , and a control group was implemented in 12 village clusters in the Nsukka Local Government Area of Enugu State , Nigeria , using epidemiologic and entomologic indicators . The appropriate material s and services were given free to all families . During the first year of study , three monitoring exercises were carried out in a r and om selection of homes where children under 5 years of age resided . Information was collected on perceived effectiveness of the interventions , condition of nets and curtains , reasons for not sleeping under nets , and recall of steps required in caring for nets and curtains . Bed nets were perceived as more effective in reducing mosquito bites compared with the two other interventions . At the last monitoring period , which occurred a few weeks before a re-impregnation exercise , respondents also perceived bed nets to be most effective in preventing malaria . These findings coincided with epidemiologic evidence . Curtains , especially those at doors , were more likely to be torn and dirty than bed nets . Although holes would not reduce the effectiveness of the insecticide , they could reduce the ' beauty ' of the curtains , a perceived benefit that initially attracted villagers to both curtains and nets . Bed net owners reported significantly less frequent use of other mosquito control measures in their homes than did members of the other groups . Finally , bed net users demonstrated increased knowledge of use and care steps than did those with curtains . These findings suggested a high level of social acceptability of bed nets , and point to the need to test their acceptability further under conditions where people would pay for nets and communities would manage distribution and re-impregnation systems Trials were undertaken in a hypoendemic area of malaria in an area bordering Vietnam , in Napo County of Guangxi Zhuang Autonomous Region , China . The aim was to compare the relative cost effectiveness of DDT residual spraying and of bednets impregnated with deltamethrin in the malaria control program . The trials were divided into three subgroups : ( 1 ) two farming areas and one coal mining area with a total population > 20,000 , where the trial consisted of mass bednets impregnated with deltamethrin 15 mg/m2 net surface once a year , ( 2 ) one farming area with a population of approximately 3,600 where DDT residual spraying at 2g/m2 was carried out twice a year in May and August ; ( 3 ) one farming area and one coal mining village with a population of > 4,000 were used as a control . The malaria vector population consisted mainly of Anopheles minimus and An . anthropophagus with a small contribution from An . sinensis . After bednets were impregnated with deltamethrin the mosquitos resting on the surface of the bednets decreased significantly , although there was less effect on the total vector population . The results showed that malaria incidence decreased significantly both in areas where impregnated bednets were used and in areas where residual spraying was undertaken . The positive IFAT rates of residents who slept under impregnated bednets decreased significantly in farming areas , especially in that area where bednet impregnation as a vector control measure had been undertaken for two years , but there was no change in the IFAT rate in DDT sprayed or control areas . ( ABSTRACT TRUNCATED AT 250 WORDS This study from two districts of Orissa State which are endemic for Plasmodium falciparum transmitted by Anopheles fluviatilis and A. culicifacies investigated the impact of dichlorodiphenyl trichloroethane ( DDT ) indoor residual spraying , in view of the ongoing discussion on phasing out DDT in India . Based on their high annual parasite incidence and logistical considerations , 26 villages in Malkangiri and 28 in Koraput district were selected for DDT spraying . For comparison , six and four unsprayed villages were chosen from the same districts . In each district , the prevalence of malaria infection and incidence of malaria fever , indoor resting density and parous rate of the vectors , and their susceptibility to DDT were monitored in six and three villages selected r and omly from the sprayed and unsprayed groups respectively . Anopheles fluviatilis was susceptible to DDT while A. culicifacies was resistant . DDT residual spraying with 1 g/m(2 ) , was carried out in October-November 2001 . Spraying 74 - 86 % of human dwellings and 100 % of cattle sheds brought down the indoor resting density of A. fluviatilis by 93 - 95 % . This was associated with a significant reduction of incidence of malaria fever as well as prevalence of malaria infection from November to February in both districts . The spraying also seemed to impact on vector longevity , and a residual effect of DDT on the sprayed walls was observed up to 10 - 12 weeks despite re-plastering . Hence DDT spraying can still be an effective tool for controlling fluviatilis-transmitted malaria . Although this species is exophilic , its nocturnal resting behaviour facilitates its contact with the sprayed surfaces . DDT is still useful for residual spraying in India , particularly in areas where the vectors are endophilic and not resistant We conducted a community-r and omized controlled trial in Pakistan to determine the efficacy of indoor residual spraying with alphacypermethrin ( ' Fendona ' , Cyanamid , NJ , USA ) , applied at 25 mg/m2 , to prevent falciparum and vivax malaria . Wettable powder ( WP ) and suspension concentrate ( SC ) formulations were tested against an unsprayed control in an irrigated rice-growing area of Sheikhupura district , Punjab province . The study area of 180 km2 was divided into nine sectors , which were assigned at r and om to control , WP , or SC treatments in replicates of 3 . Sentinel villages were selected from each sector for entomological and disease monitoring . Malaria was monitored by fortnightly active case detection ( ACD ) and by cross- sectional parasite surveys on schoolchildren . Mosquito population s were monitored by space spraying of rooms and by cattle-l and ing catches . The spray campaign took place in June 1997 and covered 96 % of compounds . During the 7 months after spraying , the incidence of falciparum malaria was 95 % lower and that of vivax malaria 80 % lower in WP-sprayed than unsprayed sectors . Similar results were obtained for sectors sprayed with the SC formulation . Cross-sectional surveys gave estimates of efficacy comparable to those obtained by ACD . Anopheles culicifacies was 80 % less abundant and A.stephensi , the predominant anopheline , was up to 68 % less abundant in sprayed areas over the 7-month period . Reductions in anopheline parous rates indicated that the single-spray treatment was effective for the entire transmission season . Sprayed surfaces lacked odour , which contributed to the popularity of the campaign . Alphacypermethrin is a promising insecticide for the control of malaria in Pakistan and South Asia generally This study compares the effectiveness and cost-effectiveness of indoor residual house-spraying ( IRS ) and insecticide-treated bednets ( ITNs ) against infection with Plasmodium falciparum as part of malaria control in the highl and s of western Kenya . Homesteads operationally targeted for IRS and ITNs during a district-based emergency response undertaken by an international relief agency were selected at r and om for evaluation . Five hundred and ninety homesteads were selected ( 200 with no vector control , 200 with IRS and 190 with ITNs ) . In July 2000 , residents in these homesteads were r and omly sample d according to three age-groups : 6 months-4 years , 5 - 15 years , and > 15 years for the presence of P. falciparum antigen ( Pf HRP-2 ) using the rapid whole blood immunochromatographic test ( ICT ) . The prevalence of P. falciparum infection amongst household members not protected by either IRS or ITN was 13 % . Sleeping under a treated bednet reduced the risk of infection by 63 % ( 58 - 68 % ) and sleeping in a room sprayed with insecticide reduced the risk by 75 % ( 73 - 76 % ) . The economic cost per infection case prevented by IRS was US$ 9 compared to US$ 29 for ITNs . This study suggests that IRS may be both more effective and cheaper than ITNs in communities subjected to low , seasonal risks of infection and as such should be considered as part of the control armamentarium for malaria prevention Malaria is one of the leading causes of morbidity and mortality in the developing world and a major public health problem in India . Disillusioned by in-house residual spraying ( IRS ) , and increasingly aware that insecticide-treated nets ( ITNs ) have proved to be effective in reducing malaria mortality and morbidity in various epidemiological setting s , policy-makers in India are keen to identify which is the more cost-effective malaria control intervention . A community r and omised controlled trial was set up in Surat to compare the effectiveness and efficiency of IRS and ITNs . Both control strategies were shown to be effective in preventing malaria over the base-case scenario of early diagnosis and prompt treatment . The mean costs per case averted for ITNs was statistically significantly lower ( Rs . 1848 , 1567 - 2209 ; US$ 52 ) than IRS ( Rs . 3121 , 2386 - 4177 , US$ 87 ) . The incremental cost-effectiveness ratio for ITNs over IRS was Rs . 799 ( US$ 22 ) . The conclusions were robust to changes in assumptions . This study exp and s the scope of recent comparative economic evaluations of ITNs and IRS , since it was carried out in a low mortality malaria endemic area In an intensely malarious area in north-east Tanzania , microencapsulated lambdacyhalothrin was used in four villages for treatment of bednets ( provided free of charge ) and in another four villages the same insecticide was used for house spraying . Another four villages received neither intervention until the end of the trial but were monitored as controls . Bioassays showed prolonged persistence of the insecticidal residues . Light traps and ELISA testing showed reduction of the malaria vector population s and the sporozoite rates , leading to a reduction of about 90 % in the entomological inoculation rate as a result of each treatment . Collection s of blood fed mosquitoes showed no diversion from biting humans to biting animals . Incidence of re-infection was measured by weekly monitoring of cohorts of 60 children per village , after clearing preexisting infection with chlorproguanil-dapsone . The vector control was associated with a reduction in probability of re-infection per child per week by 54 - 62 % , with no significant difference between the two vector control methods . Cross-sectional surveys for fever , parasitaemia , haemoglobin and weight showed association of high parasitaemia with fever and anaemia and beneficial effects of each intervention in reducing anaemia . However , passive surveillance by resident health assistants showed no evidence for reduced prevalence of fever or parasitaemia . Net treatment consumed only about one sixth as much insecticide as house spraying and it was concluded that the former intervention would work out cheaper and nets were actively dem and ed by the villagers , whereas spraying was only passively assented to In villages of northern Guadalcanal in the Solomon Isl and s , where the predominant malaria vector is An.farauti No. 1 and An.puctulatus is also involved , malaria transmission rates were compared for three zones : ( 1 ) non-intervention : 438 people in seventeen villages ; ( 2 ) residual DDT house-spraying two cycles per year : 644 people in thirty villages ; ( 3 ) bednets impregnated with permethrin 0.5 g/m2 twice per year , used by 580 people in sixteen villages . Regular DDT spraying in zones 1 and 3 had been withdrawn 18 months previously . Malariological blood smear surveys of children aged 1 - 9 years in August 1986 to January 1987 showed a mean baseline malaria parasite rate of 38 % ( 32/84 ) . By February 1988 , 18 months after introduction of impregnated bednets , the Plasmodium falciparum infection rate in children was lowest in the zone using impregnated bednets ( 21 % of 29 ) , intermediate in the untreated zone ( 29 % of 34 ) and highest in the DDT zone ( 46 % of 53 ) , but these differences were not statistically significant . P. vivax infection rates were 9 - 14 % . Using ELISA tests for malaria circumsporozoite antigen in the vectors , overall positivity rates were 0.7 % of 49,902 An.farauti and 2.54 % of 118 An.punctulatus , comprising 228 P.falciparum and 124 P.vivax infections . In the study zones , vector positivity rates were 0.93 % of 31,615 An.farauti in the untreated zone ; 0.32 % of 16,883 An.farauti in the DDT zone ; 0.07 % of 1404 An.farauti and 2.54 % of 118 An.puctulatus in the impregnated bednet zone . here was no significant correlation between malaria parasite rates in the vectors and the children . ( ABSTRACT TRUNCATED AT 250 WORDS |
12,460 | 26,633,840 | Psychiatric day clinics act as a link between inpatient and outpatient treatment in community mental healthcare . | OBJECTIVE The aim of the study was to summarize and evaluate the recent literature on treatment in psychiatric day clinics , and to assess the importance of such clinics in the current healthcare system . | Background Severe borderline personality disorder is associated with a very high psychosocial and economic burden . Current treatment guidelines suggest that several manualized treatments , including day hospital Mentalization-Based Treatment ( MBT-DH ) , are effective in these patients . However , only two r and omized controlled trials have compared manualized MBT-DH with treatment as usual . Given the relative paucity of data supporting the efficacy and cost-effectiveness of MBT-DH , the possible influence of research er allegiance in one of the trials , and potential problems with the generalization of findings to mental health systems in other countries , this multi-site r and omized trial aims to investigate the efficacy and cost-effectiveness of manualized MBT-DH compared to manualized specialist treatment as usual in The Netherl and s. Methods / design The trial is being conducted at two sites in The Netherl and s. Patients with a DSM-IV-TR diagnosis of borderline personality disorder and a score of ≥ 20 on the Borderline Personality Disorder Severity Index were r and omly allocated to MBT-DH or treatment as usual . The MBT-DH program consists of a maximum of 18 months ’ intensive treatment , followed by a maximum of 18 months of maintenance therapy . Specialist treatment as usual is provided by the City Crisis Service in Amsterdam , a service that specializes in treating patients with personality disorders , offering manualized , non-MBT interventions including family interventions , Linehan training , social skills training , and pharmacotherapy , without a maximum time limit . Patients are assessed at baseline and subsequently every 6 months up to 36 months after the start of treatment . The primary outcome measure is the frequency and severity of manifestations of borderline personality disorder as assessed by the Borderline Personality Disorder Severity Index . Secondary outcome measures include parasuicidal behaviour , symptomatic distress , social and interpersonal functioning , personality functioning , attachment , capacity for mentalizing and quality of life . Cost-effectiveness is assessed in terms of the cost per quality -adjusted life year . Outcomes will be analyzed using multilevel analyses based on intention-to-treat principles . Discussion Severe borderline personality disorder is a serious psychological disorder that is associated with high burden . This multi-site r and omized trial will provide further data concerning the efficacy and cost-effectiveness of MBT-DH for these patients .Trial registration Background / aim Day centres for people with psychiatric disabilities need to be evaluated for effectiveness in order to provide the best possible support . This study aim ed at investigating the effectiveness of a tailor-made intervention to improve day centre services for people with psychiatric disabilities . Methods The intervention was devised to bridge identified gaps in the services and lasted for 14 months . Eight centres were allotted to the intervention ( 55 attendees ) or comparison condition ( 51 attendees ) . Fidelity to the intervention and major events in the day centres were assessed . The outcomes were degree of meaningfulness found in the day centre occupations , satisfaction with the rehabilitation received , satisfaction with everyday occupations and quality of life . Results The fidelity to the intervention was good , but more positive events , such as new occupational opportunities , had taken place in the comparison units . No differences were identified between the intervention and the comparison group regarding changes from baseline to the 14-month follow-up in perceived meaningfulness among day centre occupations , satisfaction with everyday occupations or quality of life . Conclusions The intervention seemed ineffective , but the positive events in the comparison group resembled the measures included in the tailor-made interventions . This first intervention study in the day centre context has hopefully helped to generate hypotheses and methods for future research Background Although psychotherapy is considered the treatment of choice for patients with personality disorders ( PDs ) , there is no consensus about the optimal level of care for this group of patients . This study reports the results from the 6-year follow-up of the Ullevål Personality Project ( UPP ) , a r and omized clinical trial comparing outpatient individual psychotherapy with a long-term step-down treatment program that included a short-term day hospital treatment followed by combined group and individual psychotherapy . Methods The UPP included 113 patients with PDs . Outcome was evaluated after 8 months , 18 months , 3 years and 6 years and was based on a wide range of clinical measures , such as psychosocial functioning , interpersonal problems , symptom severity , and axis I and II diagnoses . Results At the 6-year follow-up , there were no statistically significant differences in outcome between the treatment groups . Effect sizes ranged from medium to large for all outcome variables in both treatment arms . However , patients in the outpatient group had a marked decline in psychosocial functioning during the period between the 3- and 6-year follow-ups ; while psychosocial functioning continued to improve in the step-down group during the same period . This difference between groups was statistically significant . Conclusions The findings suggest that both hospital-based long-term step-down treatment and long-term outpatient individual psychotherapy may improve symptoms and psychosocial functioning in poorly functioning PD patients . Social and interpersonal functioning continued to improve in the step-down group during the post-treatment phase , indicating that longer-term changes were stimulated during treatment . Trial registration NCT00378248 Background Day-hospital-based treatment programmes have been recommended for poorly functioning patients with personality disorders ( PD ) . However , more research is needed to confirm the cost-effectiveness of such extensive programmes over other , presumably simpler , treatment formats . Methods This study compared health service costs and psychosocial functioning for PD patients r and omly allocated to either a day-hospital-based treatment programme combining individual and group psychotherapy in a step-down format , or outpatient individual psychotherapy at a specialist practice . It included 107 PD patients , 46 % of whom had borderline PD , and 40 % of whom had avoidant PD . Costs included the two treatment conditions and additional primary and secondary in- and outpatient services . Psychosocial functioning was assessed using measures of global ( observer-rated GAF ) and occupational ( self-report ) functioning . Repeated assessment s over three years were analysed using mixed models . Results The costs of step-down treatment were higher than those of outpatient treatment , but these high costs were compensated by considerably lower costs of other health services . However , costs and clinical gains depended on the type of PD . For borderline PD patients , cost-effectiveness did not differ by treatment condition . Health service costs declined during the trial , and functioning improved to mild impairment levels ( GAF > 60 ) . For avoidant PD patients , considerable adjuvant health services exp and ed the outpatient format . Clinical improvements were nevertheless superior to the step-down condition . Conclusion Our results indicate that decisions on treatment format should differentiate between PD types . For borderline PD patients , the costs and gains of step-down and outpatient treatment conditions did not differ . For avoidant PD patients , the outpatient format was a better alternative , leaning , however , on costly additional health services in the early phase of treatment . Trial registration Clinical Trials Background : For patients with cluster B personality disorders there is no consensus regarding the optimal treatment setting . The aim of this study was to compare the effectiveness of different psychotherapeutic setting s for patients with cluster B personality disorders , i.e. outpatient , day hospital , and inpatient treatment . Methods : The study was conducted between March 2003 and June 2008 in 6 mental health care centres in the Netherl and s , with a sample of 207 patients with a DSM-IV-TR axis II cluster B diagnosis . Patients were assigned to 3 different setting s of psychotherapeutic treatment and effectiveness was assessed at 18 months after baseline . An intention-to-treat analysis was conducted for psychiatric symptoms ( Brief Symptom Inventory ) , psychosocial functioning ( Outcome Question naire-45 ) , and quality of life ( EQ-5D ) , using multilevel statistical modelling . As the study was non-r and omised , the propensity score method was used to control for initial differences . Results : Patients in all 3 setting s improved significantly in terms of psychiatric symptoms , social and interpersonal functioning , and quality of life 18 months after baseline . The inpatient group showed the largest improvements . The comparison of outpatient and inpatient treatment regarding psychiatric symptoms showed a marginally significant result ( p = 0.057 ) in favour of inpatient treatment . Conclusions : Patients with cluster B personality disorders improved in all investigated treatment setting s , with a trend towards larger improvements of psychiatric symptoms in the inpatient setting compared to the outpatient setting . Specialised inpatient treatment should be considered as a valuable treatment option for cluster B personality disorders , both in research and in clinical practice OBJECTIVE In 2006 the psychosomatic day hospital for the treatment of acute mental illness of elderly people opened as the first clinic of its kind in Germany . The aim of this study was to determine treatment effectiveness and identify possible effects on health care utilization . METHODS Design ed as a naturalistic study with waiting time before admission as a control condition , the primary outcome was the level of depressive symptoms as measured by the hospital anxiety and depression scale . Secondary outcomes were depressive and somatoform symptoms and syndromes as measured with the patient health question naire , patient perception of interpersonal problems and health care use before and after treatment . RESULTS After treatment significant improvement ( p<0.01 ) with moderate effect sizes ( ES ) was found in all variables from admission to discharge ( ES from 0.3 to 0.8 ) and also to follow-up ( ES from 0.2 to 0.6 ) . Improvement remained stable at follow-up . Furthermore , after psychosomatic treatment a reduction in medical service usage was visible . Number of consultations ( pre : 13 , post : 9 ) , number and length of hospital stays ( pre : 1 , 7 weeks , post : 0 , 3 weeks ) were both significantly ( p<0.001 ) reduced six months after treatment as compared to the period six months prior to treatment . CONCLUSION Results indicate that the psychosomatic day hospital treatment of the elderly is successful . Reduced usage of health care and the lower costs for day hospital treatment compared to inpatient treatment point to a positive cost-effect-ratio . Exp and ing this psychosomatic intervention would be useful in reducing the current gap in mental health care for the elderly BACKGROUND Presently few studies demonstrate improved outcomes in patients with schizophrenia treated in day rehabilitation centres . One reason is the absence of an evidence based protocol for rehabilitation in such centres . Hence further research is required to assess whether such a protocol will improve psychosocial outcomes . AIMS We performed a controlled evaluation study of a protocol based rehabilitation day program ( RDC ) for persons suffering from schizophrenia . METHODS Patients from the experimental group ( N=50 ) were treated within the RDC for a 6 month period . The control group were patients on the waiting list for the RDC . Quality of life ( MANSA ) , social functioning ( OSA ) and self-esteem ( Rosenberg ) were measured before and after the intervention . RESULTS Statistically significant improvement was shown in social functioning measured by OSA ( F(1,96)=33.7 ; p<0.001 ) , quality of life measured by MANSA ( F(1,96)=69.3 ; p<0.001 ) and self esteem measured by Rosenberg scale ( F(1,96)=84.5 ; p<0.001 ) for patients treated in the RDC compared with the control group , conversely , the control group outcomes deteriorated . CONCLUSION An evidence based protocol for rehabilitation within the RDC lead to improved social outcomes and recovery for persons suffering from schizophrenia OBJECTIVE Acute psychiatric day care has been proposed as an alternative to conventional inpatient care , yet the evidence of its effectiveness is inconsistent and based only on single-site studies in 3 countries . The aim of this multicenter r and omized controlled trial was to establish the effectiveness of acute day hospital care in a large sample across a range of mental health care systems . METHOD The trial was conducted from December 2000 to September 2003 in 5 European countries , with a sample of 1117 voluntarily admitted patients . Immediately before or very shortly after admission to the participating psychiatric facilities , patients were r and omly allocated to treatment in a day hospital or an inpatient ward . Psychopathology , treatment satisfaction , subjective quality of life , and social disabilities were assessed at admission , at discharge , and 3 and 12 months after discharge . An intention-to-treat analysis was conducted using fixed-effects linear models with structured error covariance matrices and covariates . RESULTS Day hospital care was as effective as conventional inpatient care with respect to psychopathologic symptoms , treatment satisfaction , and quality of life . It was more effective on social functioning at discharge and at the 3- and 12-month follow-up assessment s. CONCLUSION This study , which has more than doubled the existing evidence base , has shown that day hospital care is as effective on clinical outcomes as conventional inpatient care and more effective on social outcomes . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00153959 Internalized stigma is a complicating feature in the treatment of schizophrenia spectrum disorders and considerably hinders the recovery process . The empowerment and recovery-oriented program of our day clinic might contribute to a reduction in internalized stigma . The aim of the study was to explore the influence of this day clinic program on internalized stigma and other subjectively important outcome measures such as quality of life and psychopathology . Data from two groups of patients had been collected twice , at baseline and after 5 weeks . The experimental group attended the day clinic treatment ( N=40 ) and the control group waited for the day clinic treatment ( N=40 ) . The following significant differences between the two groups were found : Patients in day clinic treatment showed a reduction in internalized stigma while the control group showed a minimal increase ( Cohen 's d=0.446 ) . The experimental group as compared with the control group also showed a greater improvement in the quality of life domain psychological health ( Cohen 's d=0.6 ) and in overall psychopathology ( Cohen 's d=0.452 ) . Interestingly , changes in internalized stigma and psychological quality of life were not associated with changes in psychopathology . Results are encouraging but have to be confirmed in a r and omized design |
12,461 | 23,400,961 | FOLFIRI-B is a reasonable and effective option for stage IV CRC pretreated with oxaliplatin and not exposed to B during first-line treatment .
Its activity seems better than historical FOLFIRI-based second-line trials | Irinotecan and infusional 5-fluorouracil-based chemotherapy ( FOLFIRI ) plus bevacizumab ( FOLFIRI-B ) is one of the most effective treatments of advanced colorectal cancer ( CRC ) .
However , this schedule is regarded more extensively as first-line therapy and its efficacy has not been proven in phase III r and omised trials in oxaliplatin-pretreated patients . | PURPOSE In metastatic colorectal cancer , phase III studies have demonstrated the superiority of fluorouracil ( FU ) with leucovorin ( LV ) in combination with irinotecan or oxaliplatin over FU + LV alone . This phase III study investigated two sequences : folinic acid , FU , and irinotecan ( FOLFIRI ) followed by folinic acid , FU , and oxaliplatin ( FOLFOX6 ; arm A ) , and FOLFOX6 followed by FOLFIRI ( arm B ) . PATIENTS AND METHODS Previously untreated patients with assessable disease were r and omly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2 ) or dl-LV 400 mg/m(2 ) followed by a FU bolus 400 mg/m(2 ) and 46-hour infusion 2,400 to 3,000 mg/m(2 ) every 46 hours every 2 weeks , either with irinotecan 180 mg/m(2 ) or with oxaliplatin 100 mg/m(2 ) as a 2-hour infusion on day 1 . At progression , irinotecan was replaced by oxaliplatin ( arm A ) , or oxaliplatin by irinotecan ( arm B ) . RESULT Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI ( P = .99 ) . Median second progression-free survival ( PFS ) was 14.2 months in arm A versus 10.9 in arm B ( P = .64 ) . In first-line therapy , FOLFIRI achieved 56 % response rate ( RR ) and 8.5 months median PFS , versus FOLFOX6 which achieved 54 % RR and 8.0 months median PFS ( P = .26 ) . Second-line FOLFIRI achieved 4 % RR and 2.5 months median PFS , versus FOLFOX6 which achieved 15 % RR and 4.2 months PFS . In first-line therapy , National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis , nausea/vomiting , and grade 2 alopecia were more frequent with FOLFIRI , and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6 . CONCLUSION Both sequences achieved a prolonged survival and similar efficacy . The toxicity profiles were different BACKGROUND Polychemotherapy and biological drugs have increased therapeutic options and outcomes of advanced colorectal cancer ( CRC ) . We examined the relation between progression-free survival ( PFS ) , post-progression survival ( PPS ) and overall survival ( OS ) in trials of modern ( oxaliplatin- and irinotecan-based ) chemotherapy alone or with targeted therapies for advanced CRC . We also evaluated surrogacy of PFS and OS . PATIENTS AND METHODS A PubMed search identified 34 r and omized trials . We split the OS , PFS and PPS and evaluated the correlation between OS and either PFS or PPS . RESULTS The median PPS and PFS were 10.75 and 8.4 months , respectively . For all trials , PPS was strongly associated with OS [ regression coefficient (R2)=0.8 ; Spearman 's rank correlation coefficient (r)=0.88 ] , whereas PFS was moderately associated with OS (R2)=0.43 ; r=0.64 ) . In trials with targeted therapies , the correlation of PPS with OS was 0.88 . However , across all trials , correlation between differences in median PFS ( ΔPFS ) and median OS ( ΔOS ) is 0.59 ( P=0.0007 ) , confirming PFS/OS surrogacy . CONCLUSION Our findings indicate that in recent first-line , phase III , trials , OS becomes more associated with PPS than PFS . However , improvements in PFS are strongly associated with improvements in OS . In this setting so , PFS may be an appropriate surrogate for OS AIM To evaluate the combination of bevacizumab with infusional 5-fluorouracil ( 5-FU ) , leucovorin ( LV ) and irinotecan ( FOLFIRI ) in patients with advanced colorectal cancer ( CRC ) pretreated with combination regimens including irinotecan and oxaliplatin . METHODS Fourteen patients ( median age 56 years ) with advanced CRC , all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy , were enrolled in this study . Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1 , plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2 , and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d. RESULTS The median number of cycles of chemotherapy was six ( range 3 - 12 ) . The response rate was 28.5 % , one patient had a complete response , and three patients had a partial response . Eight patients had stable disease . The median time to progression was 3.9 mo ( 95 % CI 2.0 - 8.7 ) , and the median overall survival was 10.9 mo ( 95 % CI 9.6 - 12.1 ) . Grade 3/4 neutropenia occurred in five patients , and two of these developed neutropenic fever . Grade 3 hematuria and hematochezia occurred in one . Grade 2 proteinuria occurred in two patients . However , hypertension , bowel perforation or thromboembolic events did not occur in a total of 90 cycles . CONCLUSION Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC BACKGROUND The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined . Our aim was to investigate whether combination treatment is better than the sequential administration of the same drugs in patients with advanced colorectal cancer . METHODS In this open-label , r and omised , phase 3 trial , we r and omly assigned patients ( 1:1 ratio ) with advanced , measurable , non-resectable colorectal cancer and WHO performance status 0 - 2 to receive either first-line treatment with bolus ( 400 mg/m(2 ) ) and infusional ( 2400 mg/m(2 ) ) fluorouracil plus leucovorin ( 400 mg/m(2 ) ) ( simplified LV5FU2 regimen ) , second-line LV5FU2 plus oxaliplatin ( 100 mg/m(2 ) ) ( FOLFOX6 ) , and third-line LV5FU2 plus irinotecan ( 180 mg/m(2 ) ) ( FOLFIRI ) or first-line FOLFOX6 and second-line FOLFIRI . Chemotherapy was administered every 2 weeks . R and omisation was done central ly using minimisation ( minimisation factors were WHO performance status , previous adjuvant chemotherapy , number of disease sites , and centre ) . The primary endpoint was progression-free survival after two lines of treatment . Analyses were by intention-to-treat . This trial is registered at Clinical Trials.gov , NCT00126256 . FINDINGS 205 patients were r and omly assigned to the sequential group and 205 to the combination group . 161 ( 79 % ) patients in the sequential group and 161 ( 79 % ) in the combination group died during the study . Median progression-free survival after two lines was 10·5 months ( 95 % CI 9·6 - 11·5 ) in the sequential group and 10·3 months ( 9·0 - 11·9 ) in the combination group ( hazard ratio 0·95 , 95 % CI 0·77 - 1·16 ; p=0·61 ) . All six deaths caused by toxic effects of treatment occurred in the combination group . During first-line chemotherapy , significantly fewer severe ( grade 3 - 4 ) haematological adverse events ( 12 events in 203 patients in sequential group vs 83 events in 203 patients in combination group ; p<0·0001 ) and non-haematological adverse events ( 26 events vs 186 events ; p<0·0001 ) occurred in the sequential group than in the combination group . INTERPRETATION Upfront combination chemotherapy is more toxic and is not more effective than the sequential use of the same cytotoxic drugs in patients with advanced , non-resectable colorectal cancer . FUNDING Sanofi-Aventis France |
12,462 | 24,158,434 | Our meta- analysis suggests that a high whole grain intake , but not refined grains , is associated with reduced type 2 diabetes risk .
Our results support public health recommendations to replace refined grains with whole grains and suggest that at least two servings of whole grains per day should be consumed to reduce type 2 diabetes risk | Several studies have suggested a protective effect of intake of whole grains , but not refined grains on type 2 diabetes risk , but the dose – response relationship between different types of grains and type 2 diabetes has not been established .
We conducted a systematic review and meta- analysis of prospect i ve studies of grain intake and type 2 diabetes . | Background Control of body weight by balancing energy intake and energy expenditure is of major importance for the prevention of type 2 diabetes , but the role of specific dietary factors in the etiology of type 2 diabetes is less well established . We evaluated intakes of whole grain , bran , and germ in relation to risk of type 2 diabetes in prospect i ve cohort studies . Methods and Findings We followed 161,737 US women of the Nurses ' Health Studies ( NHSs ) I and II , without history of diabetes , cardiovascular disease , or cancer at baseline . The age at baseline was 37–65 y for NHSI and 26–46 y for NHSII . Dietary intakes and potential confounders were assessed with regularly administered question naires . We documented 6,486 cases of type 2 diabetes during 12–18 y of follow-up . Other prospect i ve cohort studies on whole grain intake and risk of type 2 diabetes were identified in search es of MEDLINE and EMBASE up to January 2007 , and data were independently extracted by two review ers . The median whole grain intake in the lowest and highest quintile of intake was , respectively , 3.7 and 31.2 g/d for NHSI and 6.2 and 39.9 g/d for NHSII . After adjustment for potential confounders , the relative risks ( RRs ) for the highest as compared with the lowest quintile of whole grain intake was 0.63 ( 95 % confidence interval [ CI ] 0.57–0.69 ) for NHSI and 0.68 ( 95 % CI 0.57–0.81 ) for NHSII ( both : p-value , test for trend < 0.001 ) . After further adjustment for body mass index ( BMI ) , these RRs were 0.75 ( 95 % CI 0.68–0.83 ; p-value , test for trend < 0.001 ) and 0.86 ( 95 % CI 0.72–1.02 ; p-value , test for trend 0.03 ) respectively . Associations for bran intake were similar to those for total whole grain intake , whereas no significant association was observed for germ intake after adjustment for bran . Based on pooled data for six cohort studies including 286,125 participants and 10,944 cases of type 2 diabetes , a two-serving-per-day increment in whole grain consumption was associated with a 21 % ( 95 % CI 13%–28 % ) decrease in risk of type 2 diabetes after adjustment for potential confounders and BMI . Conclusions Whole grain intake is inversely associated with risk of type 2 diabetes , and this association is stronger for bran than for germ . Findings from prospect i ve cohort studies consistently support increasing whole grain consumption for the prevention of type 2 diabetes BACKGROUND Certain dietary components may play a role in the prevention of type 2 diabetes . OBJECTIVE We examined prospect ively the associations between whole- and refined-grain intake and the risk of type 2 diabetes in a large cohort of men . DESIGN Men from the Health Professionals Follow-up Study without a history of diabetes or cardiovascular disease in 1986 ( n = 42898 ) were followed for < /=12 y. Intakes of whole and refined grains , measured every 4 y by use of food-frequency question naires , were used to predict subsequent type 2 diabetes risk through multivariate analysis . RESULTS We ascertained 1197 cases of incident type 2 diabetes . After adjustment for age ; physical activity ; cigarette smoking ; alcohol consumption ; family history of diabetes ; and fruit , vegetable , and energy intakes , the relative risk of type 2 diabetes was 0.58 ( 95 % CI : 0.47 , 0.70 ; P for trend < 0.0001 ) comparing the highest with the lowest quintile of whole-grain intake . The association was moderately attenuated when additionally adjusted for body mass index ( relative risk : 0.70 ; 95 % CI : 0.57 , 0.85 ; P for trend = 0.0006 ) . Intake of refined grains was not significantly associated with risk of type 2 diabetes . After further adjustment for magnesium intake , cereal fiber intake , and glycemic load , the association between whole grains and type 2 diabetes was attenuated and the trend no longer significant . CONCLUSIONS In men , a diet high in whole grains is associated with a reduced risk of type 2 diabetes in men that may be mediated by cereal fiber . Efforts should be made to replace refined-grain with whole-grain foods OBJECTIVE To examine associations between type 2 diabetes and fiber , glycemic load ( GL ) , dietary glycemic index ( GI ) , and fiber-rich foods . RESEARCH DESIGN AND METHODS This was a prospect i ve study of 36,787 men and women aged 40 - 69 years without diabetes . For all self-reported cases of diabetes at 4-year follow-up , confirmation of diagnosis was sought from medical practitioners . Case subjects were those who reported diabetes at follow-up and for whom there was no evidence that they did not have type 2 diabetes . Data were analyzed with logistic regression , adjusting for country of birth , physical activity , family history of diabetes , alcohol and energy intake , education , 5-year weight change , sex , and age . RESULTS Follow-up was completed by 31,641 ( 86 % ) participants , and 365 cases were identified . The odds ratio ( OR ) for the highest quartile of white bread intake compared with the lowest was 1.37 ( 95 % CI 1.04 - 1.81 ; P for trend = 0.001 ) . Intakes of carbohydrate ( OR per 200 g/day 0.58 , 0.36 - 0.95 ) , sugars ( OR per 100 g/day 0.61 , 0.47 - 0.79 ) , and magnesium ( OR per 500 mg/day 0.62 , 0.43 - 0.90 ) were inversely associated with incidence of diabetes , whereas intake of starch ( OR per 100 g/day 1.47 , 1.06 - 2.05 ) and dietary GI ( OR per 10 units 1.32 , 1.05 - 1.66 ) were positively associated with diabetes . These relationships were attenuated after adjustment for BMI and waist-to-hip ratio . CONCLUSIONS Reducing dietary GI while maintaining a high carbohydrate intake may reduce the risk of type 2 diabetes . One way to achieve this would be to substitute white bread with low-GI breads PURPOSE Whole grains may offer protection from diabetes by decreasing energy intake , preventing weight gain , and direct effects on insulin resistance . This study examined associations of whole and refined grains with incident type 2 diabetes ( T2D ) ascertained by self-reported medication use in a cohort of postmenopausal women . METHODS We included 72,215 women free of diabetes at baseline from the Women 's Health Initiative Observational Study . Whole grain consumption was categorized as 0 , less than 0.5 , 0.5 to 1.0 , 1.0 to less than 1.5 , 1.5 to less than 2.0 , and 2.0 or more servings per day . Proportional hazards regression was performed to estimate hazard ratios ( HR ) and 95 % confidence intervals adjusting for potential confounders . RESULTS There were 3465 cases of incident T2D over median follow-up of 7.9 years . Adjusted for age and energy intake per day , successively increasing categories of whole grain consumption were associated with statistically significant reduced risk of incident T2D ( HRs , 1.00 , 0.83 , 0.73 , 0.69 , 0.61 , and 0.57 ; P for trend < 0.0001 ) . Results were attenuated after adjustment for confounders and other dietary components . The reduction in risk of T2D was greater among nonsmokers and those who maintained their weight within 5 pounds with higher consumption of whole grains than smokers and women who gained more weight . CONCLUSIONS This large , prospect i ve study found an inverse dose-response relationship between whole grain consumption and incident T2D in postmenopausal women Seven men with well-controlled , noninsulin-dependent ( type 2 ) diabetes ingested on two different mornings , in r and om order , meals with or without a 5.0-g sodium alginate supplement ( algae-isolate , 75 % soluble fiber ) . The meals contained similar amounts of digestible carbohydrates , fat and protein . The gastric emptying rate of the meal containing sodium alginate , measured by detection of 51Cr mixed into the meals , was significantly slower than that of the fiber-free meal . Sodium alginate also induced significantly lower postpr and ial rises in blood glucose , serum insulin and plasma C-peptide . The diminished glucose response after the addition of sodium alginate could be correlated to the delayed gastric emptying rate induced by the fiber ( rs = 0.92 , P less than 0.01 ) BACKGROUND Dietary carbohydrates may influence the development of type 2 ( non-insulin-dependent ) diabetes , for example , through effects on blood glucose and insulin concentrations . OBJECTIVE We examined the relations of baseline intake of carbohydrates , dietary fiber , dietary magnesium , and carbohydrate-rich foods and the glycemic index with incidence of diabetes . DESIGN This was a prospect i ve cohort study of 35988 older Iowa women initially free of diabetes . During 6 y of follow-up , 1141 incident cases of diabetes were reported . RESULTS Total grain , whole-grain , total dietary fiber , cereal fiber , and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables . Multivariate-adjusted relative risks of diabetes were 1.0 , 0.99 , 0.98 , 0.92 , and 0.79 ( P for trend : 0.0089 ) across quintiles of whole-grain intake ; 1.0 , 1.09 , 1.00 , 0.94 , and 0.78 ( P for trend : 0.005 ) across quintiles of total dietary fiber intake ; and 1.0 , 0.81 , 0.82 , 0.81 , and 0.67 ( P for trend : 0.0003 ) across quintiles of dietary magnesium intake . Intakes of total carbohydrates , refined grains , fruit and vegetables , and soluble fiber and the glycemic index were unrelated to diabetes risk . CONCLUSION These data support a protective role for grains ( particularly whole grains ) , cereal fiber , and dietary magnesium in the development of diabetes in older women BACKGROUND Rye bread has a beneficial effect on the postpr and ial insulin response in healthy subjects . The role of rye fiber in insulin and glucose metabolism is not known . OBJECTIVE The aim of the study was to determine the effect of the content of rye fiber in rye breads on postpr and ial insulin and glucose responses . DESIGN Nineteen healthy postmenopausal women aged 61 + /- 1 y , with a body mass index ( in kg/m(2 ) ) of 26.0 + /- 0.6 , and with normal glucose tolerance participated in the study . The test products were refined wheat bread ( control ) , endosperm rye bread , traditional rye bread , and high-fiber rye bread ; each bread provided 50 g available carbohydrate and was served with breakfast . Plasma glucose , insulin , glucose-dependent insulinotropic polypeptide , glucagon-like peptide 1 , and serum C-peptide were measured in fasting and 8 postpr and ial blood sample s. In vitro starch hydrolysis and the microscopic structure of the breads were also determined . RESULTS Postpr and ial insulin , glucose-dependent insulinotropic polypeptide , and C-peptide responses to the rye breads were significantly lower than the response to the control ; no significant differences in insulin and C-peptide responses to the rye breads were found . Glucose and glucagon-like peptide 1 responses to the rye breads were not significantly different from those to the control , except at 150 and 180 min . In vitro starch hydrolysis was slower in all rye breads than in the control , and the structure of continuous matrix and starch granules differed between the rye and control breads . CONCLUSION Total fiber content does not explain the lower postpr and ial insulin response to rye bread than to wheat bread , but structural differences between rye and wheat breads might BACKGROUND Epidemiologic studies that directly examine changes in whole-grain consumption in relation to weight gain are sparse , and characterization of this association has been obscured by method ologic inconsistencies in the assessment of whole grains . OBJECTIVE We aim ed to ascertain the associations between changes in new quantitative estimates of whole-grain intake and 8-y weight gain among US men . DESIGN The study was conducted in a prospect i ve cohort of 27 082 men aged 40 - 75 y at baseline in 1986 . Data on lifestyle factors were obtained periodically by using self-reported question naires , and participants measured and reported their body weight in 1986 and 1994 . RESULTS In multivariate analyses , an increase in whole-grain intake was inversely associated with long-term weight gain ( P for trend < 0.0001 ) . A dose-response relation was observed , and for every 40-g/d increment in whole-grain intake from all foods , weight gain was reduced by 0.49 kg . Bran that was added to the diet or obtained from fortified-grain foods further reduced the risk of weight gain ( P for trend = 0.01 ) , and , for every 20 g/d increase in intake , weight gain was reduced by 0.36 kg . Changes in cereal and fruit fiber were inversely related to weight gain . No associations were observed between changes in refined-grain or added germ consumption and body weight . CONCLUSIONS The increased consumption of whole grains was inversely related to weight gain , and the associations persisted after changes in added bran or fiber intakes were accounted for . This suggests that additional components in whole grains may contribute to favorable metabolic alterations that may reduce long-term weight gain To determine the relations of diet with risk of clinical noninsulin-dependent diabetes , we analyzed data from a prospect i ve cohort of 84360 US women . During 6 y of follow-up we identified 702 definite incident cases . Because body mass index ( BMI ) is a powerful risk factor for diabetes , we examined the relations of fat ( including type ) , fiber , sucrose , and other components of diet to risk of diabetes , among women with BMI s ( in kg/m2 ) less than 29 kg/m2 . After controlling for body mass index , previous weight change , and alcohol intake , we observed no associations between intakes of energy , protein , sucrose , carbohydrate , or fiber and risk of diabetes . Compared with women in the lowest quintile of energy-adjusted intake , and relative risks ( and tests for trend ) for those in the highest quintile were 0.61 ( P trend = 0.03 ) for vegetable fat , 0.62 ( P trend = 0.008 ) for potassium , 0.70 ( P trend = 0.005 ) for calcium , and 0.68 ( P trend = 0.02 ) for magnesium . These inverse associations were attenuated among obese women ( BMI s greater than or equal to 29 ) BACKGROUND Although increased consumption of dietary fiber and grain products is widely recommended to maintain healthy body weight , little is known about the relation of whole grains to body weight and long-term weight changes . OBJECTIVE We examined the associations between the intakes of dietary fiber and whole- or refined-grain products and weight gain over time . DESIGN In a prospect i ve cohort study , 74,091 US female nurses , aged 38 - 63 y in 1984 and free of known cardiovascular disease , cancer , and diabetes at baseline , were followed from 1984 to 1996 ; their dietary habits were assessed in 1984 , 1986 , 1990 , and 1994 with vali date d food-frequency question naires . Using multiple models to adjust for covariates , we calculated average weight , body mass index ( BMI ; in kg/m(2 ) ) , long-term weight changes , and the odds ratio of developing obesity ( BMI > or = 30 ) according to change in dietary intake . RESULTS Women who consumed more whole grains consistently weighed less than did women who consumed less whole grains ( P for trend < 0.0001 ) . Over 12 y , those with the greatest increase in intake of dietary fiber gained an average of 1.52 kg less than did those with the smallest increase in intake of dietary fiber ( P for trend < 0.0001 ) independent of body weight at baseline , age , and changes in covariate status . Women in the highest quintile of dietary fiber intake had a 49 % lower risk of major weight gain than did women in the highest quintile ( OR = 0.51 ; 95 % CI : 0.39 , 0.67 ; P < 0.0001 for trend ) . CONCLUSION Weight gain was inversely associated with the intake of high-fiber , whole-grain foods but positively related to the intake of refined-grain foods , which indicated the importance of distinguishing whole-grain products from refined-grain products to aid in weight control To define the type of dietary fibre of fibre analogue with the greatest potential use in diabetic treatment , groups of four to six volunteers underwent 50-g glucose tolerance tests ( GTT ) with and without the addition of either guar , pectin , gum tragacanth , methylcellulose , wheat bran , or cholestyramine equivalent to 12 g fibre . The addition of each substance significantly reduced blood glucose concentration at one or more points during the GTT and generally reduced serum insulin concentrations . The greatest flattening of the glucose response was seen with guar , but this effect was abolished when hydrolysed non-viscous guar was used . The reduction in the mean peak rise in blood glucose concentration for each substance correlated positively with its viscosity ( r = 0.926 ; P less than 0.01 ) , as did delay in mouth-to-caecum transit time ( r = 0.885 ; P less than 0.02 ) . Viscous types of dietary fibre are therefore most likely to be therapeutically useful in modifying postpr and ial hyperglycaemia Background / Objectives : There is still a need for scientific evidence about which foods characterize a healthy diet in terms of primary prevention of major chronic diseases . Therefore , we aim ed to give a comprehensive overview on health-related foods , based on 8 years of follow-up of the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Potsdam study .Subjects/ Methods : We used data from 23 531 participants of the EPIC-Potsdam study to analyse the associations between 45 single food groups and risk of major chronic diseases , namely , cardiovascular diseases ( CVD ) , type 2 diabetes and cancer using multivariable-adjusted Cox regression . Habitual dietary intake was assessed at baseline using food-frequency question naires . Incident chronic diseases were determined by self-administered follow-up question naires and medically verified , based on inquiry to treating physicians , cancer registries or through death certificates . Results : During follow-up , 363 incident CVD , 837 type 2 diabetes and 844 cancer cases were identified . Higher intakes of whole-grain bread , raw vegetables , coffee and cakes and cookies were found to be significantly associated with a lower risk of chronic diseases . Conversely , higher intakes of low-fat dairy , butter , red meat and sauce were associated with higher risks of chronic diseases . Conclusion : Overall , a healthy diet was characterized by a high consumption of whole-grain bread , raw vegetables and a low consumption of red meat and possibly butter , which is generally in line with previous findings . The paradoxical findings concerning the potential health benefit of coffee as well as cakes and cookies are interesting and should be investigated further The aim of the study was to examine the association of dietary carbohydrates and glycaemic load with the risk of type 2 diabetes among an urban adult Asian Indian population . Adult subjects aged > 20 years ( n 1843 ) were r and omly selected from the Chennai Urban Rural Epidemiology Study , in Chennai city in southern India . Dietary carbohydrates , glycaemic load and food groups were assessed using FFQ . Oral glucose tolerance tests were performed using 75 g glucose in all subjects . Diagnosis of diabetes was based on WHO Consulting Group criteria . OR for newly detected diabetes were calculated for carbohydrates , glycaemic load and specific food groups comparing subjects in the highest with those in the lowest quartiles , after adjustment for potential confounders such as age , sex , BMI , family history of diabetes , physical activity , current smoking , alcohol consumption and relevant dietary factors . We identified 156 ( 8.5 % ) newly diagnosed cases of type 2 diabetes . Refined grain intake was positively associated with the risk of type 2 diabetes ( OR 5.31 ( 95 % CI 2.98 , 9.45 ) ; P < 0.001 ) . In the multivariate model , after adjustment for potential confounders , total carbohydrate ( OR 4.98 ( 95 % CI 2.69 , 9.19 ) , P < 0.001 ) , glycaemic load ( OR 4.25 ( 95 % CI 2.33 , 7.77 ) ; P < 0.001 ) and glycaemic index ( OR 2.51 ( 95 % CI 1.42 , 4.43 ) ; P = 0.006 ) were associated with type 2 diabetes . Dietary fibre intake was inversely associated with diabetes ( OR 0.31 ( 95 % CI 0.15 , 0.62 ) ; P < 0.001 ) . In urban south Indians , total dietary carbohydrate and glycaemic load are associated with increased , and dietary fibre with decreased , risk of type 2 diabetes To determine the part played by altered gastric emptying in the modification of glucose absorption by gel fibres , glucose tolerance tests were done in seven healthy volunteers with and without the addition of pectin to the ingested glucose solution and after pharmacological inhibition of gastric emptying with propantheline . Compared with the controls , pectin significantly reduced blood-glucose . Propantheline had a similar but more pronounced effect . Pectin and guar gum did not substantially alter glucose tolerance in a patient who had had total gastrectomy . In a further investigation , gastric emptying and paracetamol absorption were studied simultaneously in fourteen subjects . In eight of these the study was repeated after addition of guar gum and pectin to the ingested paracetamol . Both gastric emptying and paracetamol absorption were slower after gel fibre but the total absorption of the drug , reflected in urinary recovery , was not significantly reduced . The results suggest that the effects of guar gum and pectin on glucose tolerance and paracetamol absorption could be due simply to alteration in the rate of gastric emptying OBJECTIVE Prospect i ve studies have suggested that substituting whole grain for refined grain products may lower the risk of overweight and obesity . Breakfast cereal intake is a major source of whole and refined grains and has also been associated with having a lower BMI . The aim of this study was to prospect ively assess the association between whole and refined grain breakfast cereal intakes and risk of overweight ( BMI > or= 25 kg/m(2 ) ) and weight gain . RESEARCH METHODS AND PROCEDURES We examined 17,881 U.S. male physicians 40 to 84 years of age in 1982 who were free of cardiovascular disease , diabetes mellitus , and cancer at baseline and reported measures of breakfast cereal intake , weight , and height . RESULTS Over 8 and 13 years of follow-up , respectively , men who consumed breakfast cereal , regardless of type , consistently weighed less than those who consumed breakfast cereals less often ( p value for trend = 0.01 ) . Whole and refined grain breakfast cereal intake was inversely associated with body weight gain over 8 years , after adjustment for age , smoking , baseline BMI , alcohol intake , physical activity , hypertension , high cholesterol , and use of multivitamins . Compared with men who rarely or never consumed breakfast cereals , those who consumed > or=1 serving/d of breakfast cereals were 22 % and 12 % less likely to become overweight during follow-up periods of 8 and 13 years ( relative risk , 0.78 and 0.88 ; 95 % confidence interval , 0.67 to 0.91 and 0.76 to 1.00 , respectively ) . DISCUSSION BMI and weight gain were inversely associated with intake of breakfast cereals , independently of other risk factors The authors investigated the association of dietary patterns and type 2 diabetes in a 4-year prospect i ve study of 36,787 adults in the Melbourne Collaborative Cohort Study ( 1990 - 1994 ) . A total of 31,641 ( 86 % ) participants completed follow-up , and 365 cases were identified . Four factors with eigenvalues of greater than 2 were identified using the principal factor method with 124 foods/beverages , followed by orthogonal rotation . Variables with factor loadings having absolute values of 0.3 or greater were used in interpreting the factors . Odds ratios for diabetes incidence across quintiles of factor scores were computed by use of logistic regression , adjusting for age , energy intake , family history of diabetes , country of birth , and other factor scores . Factor 1 , characterized by olive oil , salad vegetables , and legumes and by avoidance of sweet bakery items , margarine , and tea , was associated with country of birth but not with diabetes . Factor 2 , characterized by salad and cooked vegetables , was inversely associated with diabetes . Factor 3 , characterized by meats and fatty foods , was associated with increased diabetes risk . A range of fruits loaded strongly on factor 4 , which showed little association with diabetes . Avoidance of a dietary pattern including meats and fatty foods , as well as adherence to a pattern including salad and cooked vegetables , is recommended OBJECTIVE We aim ed to develop a precise risk score for the screening of large population s for individuals at high risk of developing type 2 diabetes based on noninvasive measurements of major risk factors in German study population s. RESEARCH DESIGN AND METHODS A prospect i ve cohort study ( European Prospect i ve Investigation into Cancer and Nutrition [EPIC]-Potsdam study ) of 9,729 men and 15,438 women aged 35 - 65 years was used to derive a risk score predicting incident type 2 diabetes . Multivariate Cox regression model coefficients were used to weigh each variable in the calculation of the score . Data from the EPIC-Heidelberg , the Tübingen Family Study for Type 2 Diabetes ( TUF ) , and the Metabolic Syndrome Berlin Potsdam ( MeSyBePo ) study were used to vali date this score . RESULTS Information on age , waist circumference , height , history of hypertension , physical activity , smoking , and consumption of red meat , whole-grain bread , coffee , and alcohol formed the German Diabetes Risk Score ( mean 446 points [ range 118 - 983 ] ) . The probability of developing diabetes within 5 years in the EPIC-Potsdam study increased from 0.3 % for 300 to 23.2 % for 750 score points . The area under the receiver-operator characteristic ( ROC ) curve was 0.84 in the EPIC-Potsdam and 0.82 in the EPIC-Heidelberg studies . Correlation coefficients between the German Diabetes Risk Score and insulin sensitivity in nondiabetic individuals were -0.56 in the TUF and -0.45 in the MeSyBePo studies . ROC values for undiagnosed diabetes were 0.83 in the TUF and 0.75 in the MeSyBePo studies . CONCLUSIONS The German Diabetes Risk Score ( available at www.dife.de ) is an accurate tool to identify individuals at high risk for or with undiagnosed type 2 diabetes OBJECTIVES This study examined the association between intake of whole vs refined grain and the risk of type 2 diabetes mellitus . METHODS We used a food frequency question naire for repeated dietary assessment s to prospect ively evaluate the relation between whole-grain intake and the risk of diabetes mellitus in a cohort of 75,521 women aged 38 to 63 years without a previous diagnosis of diabetes or cardiovascular disease in 1984 . RESULTS During the 10-year follow-up , we confirmed 1879 incident cases of diabetes mellitus . When the highest and the lowest quintiles of intake were compared , the age and energy-adjusted relative risks were 0.62 ( 95 % confidence interval [ CI ] = 0.53 , 0.71 , P trend < .0001 ) for whole grain , 1.31 ( 95 % CI = 1.12 , 1.53 , P trend = .0003 ) for refined grain , and 1.57 ( 95 % CI = 1.36 , 1.82 , P trend < .0001 ) for the ratio of refined- to whole-grain intake . These findings remained significant in multivariate analyses . The findings were most evident for women with a body mass index greater than 25 and were not entirely explained by dietary fiber , magnesium , and vitamin E. CONCLUSIONS These findings suggest that substituting whole- for refined-grain products may decrease the risk of diabetes mellitus BACKGROUND Refined carbohydrates have been suggested to deteriorate glucose metabolism ; however , whether persons with elevated intakes of white rice , which is a major staple food for the Japanese , experience increased risk of developing type 2 diabetes remains unclear . OBJECTIVE We prospect ively investigated the association between white rice intake and risk of type 2 diabetes . DESIGN Participants were 25,666 men and 33,622 women aged 45 - 75 y who participated in the second survey of the Japan Public Health Center-based Prospect i ve Study and who had no prior history of diabetes . We ascertained food intake by using a vali date d 147-item food-frequency question naire . Odds ratios of self-reported , physician-diagnosed type 2 diabetes over 5 y were estimated by using logistic regressions . RESULTS A total of 1103 new cases of type 2 diabetes were self-reported . There was a significant association between rice intake and an increased risk of type 2 diabetes in women ; the multivariate-adjusted odds ratio for the highest compared with lowest quartiles of rice intake was 1.65 ( 95 % CI : 1.06 , 2.57 ; P for trend = 0.005 ) . In men , the association was unclear , although there was a suggestion of a positive association in persons who were not engaged in strenuous physical activity ( P for trend = 0.08 ) . CONCLUSIONS Elevated intake of white rice is associated with an increased risk of type 2 diabetes in Japanese women . The finding that is suggestive of a positive association of rice intake in physically inactive men deserves further investigation BACKGROUND High whole-grain intake has been reportedly associated with reduced risk of developing type 2 diabetes ( T2D ) , which is an effect possibly subject to genetic effect modification . Confirmation in prospect i ve studies and investigations on the impact on prediabetes is needed . OBJECTIVES In a prospect i ve population -based study , we investigated whether a higher intake of whole grain protects against the development of prediabetes and T2D and tested for modulation by polymorphisms of the TCF7L2 gene . DESIGN We examined the 8 - 10-y incidence of prediabetes ( impaired glucose tolerance , impaired fasting glucose , or the combination of both ) and T2D in relation to the intake of whole grain . Baseline data were available for 3180 women and 2297 men aged 35 - 56 y. RESULTS A higher intake of whole grain ( > 59.1 compared with < 30.6 g/d ) was associated with a 34 % lower risk to deteriorate in glucose tolerance ( to prediabetes or T2D ; women and men combined ) . The association remained after adjustments for age , family history of diabetes , BMI , physical activity , smoking , education , and blood pressure ( OR : 0.78 ; 95 % CI : 0.63 , 0.96 ) . Risk reduction was significant in men ( OR : 0.65 ; 95 % CI : 0.49 , 0.85 ) but not in women . Associations were significant for prediabetes per se ( all , OR : 0.73 ; 95 % CI : 0.56 , 0.94 ; men , OR : 0.57 ; 95 % CI : 0.40 , 0.80 ) . The intake of whole grain correlated inversely with insulin resistance ( HOMA-IR ) . The impact of whole-grain intake was undetectable in men who harbored diabetogenic polymorphisms of the TCF7L2 gene . CONCLUSIONS A higher intake of whole grain is associated with decreased risk of deteriorating glucose tolerance including progression from normal glucose tolerance to prediabetes by mechanisms likely tied to effects on insulin sensitivity . Effect modifications by TCF7L2 genetic polymorphisms are supported BACKGROUND Small-scale , short-term intervention studies have suggested that plasma alkylresorcinol ( AR ) concentrations may be biomarkers of whole grain ( WG ) wheat and rye intakes . OBJECTIVE The objective was to determine whether plasma AR concentrations reflect self-reported WG food intake in a 16-wk WG intervention study and to establish which phenotypic characteristics influence plasma AR concentrations . DESIGN In a r and omized parallel-group dietary intervention study , 316 overweight and obese participants with a WG intake of < 30 g/d were recruited and r and omly assigned to 1 of 3 groups : control ( no dietary change ) , intervention 1 ( 60 g WG/d for 16 wk ) , or intervention 2 ( 60 g WG/d for 8 wk followed by 120 g WG/d for 8 wk ) . Fasting blood sample s were collected at baseline , 8 wk , and 16 wk for the measurement of plasma lipids and ARs . RESULTS Plasma sample s from 266 study completers were analyzed . Total plasma AR concentrations increased with the WG intervention and could be used to distinguish between control subjects and those who consumed 60 or 120 g WG , but not between those who consumed 60 and 120 g WG . Plasma AR concentrations were higher in men , were positively associated with plasma triglyceride concentrations , and were negatively associated with nonesterified fatty acids . CONCLUSIONS Plasma AR concentrations were correlated with WG intake and could be used to distinguish between low- and high-WG consumers . Sex and plasma lipid concentrations independently influenced plasma AR concentrations , although plasma triglycerides may explain higher concentrations in men . This trial is registered as IS RCT no. 83078872 BACKGROUND Because of differences in processing and nutrients , brown rice and white rice may have different effects on risk of type 2 diabetes mellitus . We examined white and brown rice consumption in relation to type 2 diabetes risk prospect ively in the Health Professionals Follow-up Study and the Nurses ' Health Study I and II . METHODS We prospect ively ascertained and up date d diet , lifestyle practice s , and disease status among 39,765 men and 157,463 women in these cohorts . RESULTS After multivariate adjustment for age and other lifestyle and dietary risk factors , higher intake of white rice ( > or = 5 servings per week vs < 1 per month ) was associated with a higher risk of type 2 diabetes : pooled relative risk ( 95 % confidence interval [ CI ] ) , 1.17 ( 1.02 - 1.36 ) . In contrast , high brown rice intake ( > or = 2 servings per week vs < 1 per month ) was associated with a lower risk of type 2 diabetes : pooled relative risk , 0.89 ( 95 % CI , 0.81 - 0.97 ) . We estimated that replacing 50 g/d ( cooked , equivalent to one-third serving per day ) intake of white rice with the same amount of brown rice was associated with a 16 % ( 95 % CI , 9%-21 % ) lower risk of type 2 diabetes , whereas the same replacement with whole grains as a group was associated with a 36 % ( 30%-42 % ) lower diabetes risk [ corrected ] . CONCLUSIONS Substitution of whole grains , including brown rice , for white rice may lower risk of type 2 diabetes . These data support the recommendation that most carbohydrate intake should come from whole grains rather than refined grains to help prevent type 2 diabetes Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control . However , the underst and ing of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited . The aim of the present study was to examine intakes of macronutrients , fibre and protein sources in relation to incident type 2 diabetes . In total , 27 140 individuals , aged 45 - 74 years , from the population -based Malmö Diet and Cancer cohort , were included . Dietary data were collected with a modified diet history method , including registration of cooked meals . During 12 years of follow-up , 1709 incident type 2 diabetes cases were identified . High protein intake was associated with increased risk of type 2 diabetes ( hazard ratio ( HR ) 1.27 for highest compared with lowest quintile ; 95 % CI 1.08 , 1.49 ; P for trend = 0.01 ) . When protein consumption increased by 5 % of energy at the expense of carbohydrates ( HR 1.20 ; 95 % CI 1.09 , 1.33 ) or fat ( HR 1.21 ; 95 % CI 1.09 , 1.33 ) , increased diabetes risk was observed . Intakes in the highest quintiles of processed meat ( HR 1.16 ; 95 % CI 1.00 , 1.36 ; P for trend = 0.01 ) and eggs ( HR 1.21 ; 95 % CI 1.04 , 1.41 ; P for trend = 0.02 ) were associated with increased risk . Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes ( HR 0.84 ; 95 % CI 0.73 , 0.98 ; P for trend = 0.004 ) . In conclusion , results from the present large population -based prospect i ve study indicate that high protein intake is associated with increased risk of type 2 diabetes . Replacing protein with carbohydrates may be favourable , especially if fibre-rich breads and cereals are chosen as carbohydrate sources OBJECTIVE To examine the association between breakfast cereal consumption and the risk of type 2 diabetes ( DM ) . RESEARCH METHODS AND PROCEDURES We analyzed prospect ively data from 21,152 male participants of the Physicians ' Health Study I. Consumption of breakfast cereals was estimated using an abbreviated food question naire , and incident DM was ascertained through yearly follow-up question naires . RESULTS The average age was 53.6 + /- 9.4 years ( range , 39.7 to 85.9 ) during the initial assessment of cereal intake ( 1981 to 1983 ) . During a mean follow-up of 19.1 years , 1958 cases of DM occurred . The crude incidence rates of DM were 57.7 , 53.8 , 43.5 , and 35.4 cases/10,000 person-years for people reporting breakfast cereal intake of 0 , < or=1 , 2 to 6 , and > or=7 servings/wk , respectively . In a Cox regression model adjusting for age , cigarette smoking , BMI , physical activity , vegetable consumption , and alcohol intake , hazard ratios ( 95 % confidence interval ) for DM were 1.0 ( reference ) , 0.89 ( 0.79 to 1.00 ) , 0.76 ( 0.67 to 0.86 ) , and 0.63 ( 0.55 to 0.72 ) from the lowest to the highest category of cereal consumption , respectively ( p for trend < 0.0001 ) . In secondary analyses , the inverse association between cereal intake and DM was stronger with whole-grain than refined cereals . DISCUSSION These results suggest that intake of breakfast cereals might confer a lower risk of DM . Consumption of whole-grain products may help lower the risk of DM AIMS Diet and physical activity interventions can prevent diabetes in those at high risk due to impaired glucose tolerance . We determined whether simple measures of physical activity and diet predicted incident diabetes and enhanced prediction by known risk factors including age , body mass index and family history . METHODS This was a population -based prospect i ve cohort study ( EPIC-Norfolk ) . Participants aged 40 - 79 years ( n = 25,633 ) attended a health check between 1993 and 1998 and completed diet and activity question naires . We assessed the association between simple behavioural indices of physical activity and diet derived from the question naires as well as known risk score variables with incident diabetes at follow-up ( mean 4.6 years ) . We developed a new diabetes risk score incorporating simple behavioural indices in a r and omly selected half of the EPIC data set using forward step-wise multivariate logistic regression , and tested this score in the remaining half . We compared existing and new scores using receiver-operating characteristic ( ROC ) curves . RESULTS There were 417 incident cases of diabetes during 115,137 years of follow-up . A simple physical activity index independently predicted risk of diabetes . Eating one or more daily portion of vegetables , fresh fruit and wholemeal bread was associated with reduced risk ; whilst eating meat products was associated with increased risk . The area under the ROC curves for the new and original score was the same ( 76.3 % ) . CONCLUSIONS Simple indices of diet and activity are feasible to collect , predict future diabetes risk and might enhance routine data collection in primary care . However , they do not improve the prediction of risk scores based on known risk factors Whole grains are known to influence postpr and ial glucose response and insulin dem and and are inversely associated with diabetes risk . Genetic variation of the transcription factor-7-like 2 encoding gene ( TCF7L2 ) is assumed to promote an early insulin secretory defect and has been consistently attributed to the risk of developing type 2 diabetes . The present study examined the hypothesis that the protective effect of whole grains might be attenuated in the presence of the rs7903146 risk-conferring T-allele . We employed a case-cohort study of 2318 r and omised individuals and 724 incident type 2 diabetes cases from the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort . Multivariate Cox regression was used to estimate relative risks of diabetes including product terms testing for the genotype-specific effect modification of dietary whole grain . Dietary intake of whole grains was assessed by a vali date d FFQ . The TCF7L2 rs7903146 T-allele was associated with type 2 diabetes ( hazard ratio=1.51 ; 95 % CI 1.21 , 1.87 ) and modified the inverse association between whole-grain intake and diabetes risk ( P=0.016 for interaction ) . While whole-grain intake was inversely associated with diabetes risk among rs7903146 CC homozygote carriers ( hazard ratio for 50 g portion per d=0.86 ; 95 % CI 0.75 , 0.99 ) , the T-allele negated the protective effect of whole-grain intake ( hazard ratio among T-allele carriers for 50 g portion per d=1.08 ; 95 % CI 0.96 , 1.23 ) . These data provide evidence that the beneficial effect of whole-grain intake on diabetes risk is modified by TCF7L2 rs7903146 In premenopausal women , elevated C-reactive protein ( CRP ) concentrations have been associated with an increased risk of negative reproductive outcomes . Whole grain consumption has been associated with lower CRP concentrations in older women ; however , less is known about this relationship in younger women . We investigated whether whole grain intake was associated with serum high sensitivity CRP ( hs-CRP ) concentrations in young women . BioCycle was a prospect i ve cohort study conducted at the University of Buffalo from 2005 to 2007 , which followed 259 healthy women aged 18 - 44 y for < or= 2 menstrual cycles . hs-CRP concentrations were measured longitudinally < or= 8 times/cycle with visits st and ardized to menstrual cycle phase . Whole grain intake was estimated by 24-h recalls < or= 4 times/cycle . Servings were defined as 16 g or 125 mL of a 100 % whole grain food . Whole grain intake was inversely associated with hs-CRP concentrations after adjusting for age , race , BMI , illness , and antiinflammatory drug use . Consumers of between 0 and 1 serving/d of whole grains had , on average , 11.5 % lower hs-CRP concentrations ( P = 0.02 ) and consumers of > or= 1 serving/d had 12.3 % lower hs-CRP concentrations ( P = 0.02 ) compared with nonconsumers . Women who consumed > or= 1 serving/d of whole grain had a lower probability of having moderate ( P = 0.008 ) or elevated ( P = 0.001 ) hs-CRP according to the AHA criteria compared with nonconsumers . Given that elevated concentrations of hs-CRP have been linked to adverse reproductive outcomes and pregnancy complications , interventions targeting whole grain consumption may have the potential to improve health status among young women Background : R and omized trials have examined short-term effects of lifestyle interventions for diabetes prevention only among high-risk individuals . Prospect i ve studies have examined the associations between lifestyle factors and diabetes in healthy population s but have not characterized the intervention . We estimated the long-term effects of hypothetical lifestyle interventions on diabetes in a prospect i ve study of healthy women , using the parametric g-formula . Methods : Using data from the Nurses ’ Health Study , we followed 76,402 women from 1984 to 2008 . We estimated the risk of type 2 diabetes under eight hypothetical interventions : quitting smoking , losing weight by 5 % every 2 years if overweight/obese , exercising at least 30 minutes a day , eating less than three servings a week of red meat , eating at least two servings a day of whole grain , drinking two or more cups of coffee a day , drinking five or more grams of alcohol a day , and drinking less than one serving of soda a week . Results : The 24-year risk of diabetes was 9.6 % under no intervention and 4.3 % when all interventions were imposed ( 55 % lower risk [ 95 % confidence interval = 47 to 63 % ] ) . The most effective interventions were weight loss ( 24 % lower risk ) , physical activity ( 19 % ) , and moderate alcohol use ( 19 % ) . Overweight/obese women would benefit the most , with 10.8 percentage point reduction in 24-year risk of diabetes . The validity of these estimates relies on the absence of unmeasured confounding , measurement error , and model misspecification . Conclusion : A combination of dietary and nondietary lifestyle modifications , begun in midlife or later in relatively healthy women , could have prevented at least half of the cases of type 2 diabetes in this cohort of U.S. women |
12,463 | 28,211,296 | Conclusion In summary , the general level of evidence supports the recommendation that the use of medical therapy with Micronized Purified Flavonoid Fraction has beneficial outcomes without serious adverse events .
In the United States , diosmiplex is the only available prescription formulation of Micronized Purified Flavonoid Fraction . | Scope A systematic review of the clinical literature concerning medical management of chronic venous disease with the venoactive therapy Micronized Purified Flavonoid Fraction was conducted in addition to an investigation of the hemodynamics and mechanism of chronic venous disease .
Methods The systematic review of the literature focused on the use of Micronized Purified Flavonoid Fraction ( diosmin ) which has recently become available in the US , in the management of chronic venous disease .
The primary goal was to assess the level of evidence of the role of Micronized Purified Flavonoid Fraction in the healing of ulcers , and secondarily on the improvement of the symptoms of chronic venous disease such as edema .
It is derived from the rinds of oranges and is categorized as a medical food and not as a drug ; and may be a particularly attractive therapy for many chronic venous disease patients because of its favorable safety profile . | Quality of life may be considerably reduced in patients who are suffering from chronic lower limb venous insufficiency , although existing generic quality of life instruments ( NHP , SF-36 or SIP ) can not completely identify their specific complaints . The Chronic Venous Insufficiency Question naire ( CIVIQ ) has been developed by iterative process . First , a pilot group of 20 patients was used to identify a number of important features of quality of life affected by venous insufficiency , other than physical symptoms of discomfort . A second study involving 2,001 subjects was used to reduce the number of items . Subjects were asked to score both the severity of their problems and the importance they attributed to each problem on a 5-point Likert scale . The importance items found in patients with venous insufficiency were subjected to factorial analyses ( PCA , PAF ) . The final version is a 20-item self-administered question naire which explores four dimensions : psychological , physical and social functioning and pain . Internal consistency of the question naire was vali date d for each dimension ( Cronbach 's alpha > 0.820 for three out of four factors ) . Reproducibility was confirmed in a 60 patient test-retest study . Pearson 's correlation coefficients for both the four dimension subscales and for the global score at 2-week intervals were greater than 0.940 . Finally , the question naire was tested in a r and omized clinical trial of 934 patients in order to assess responsiveness and the convergent validity of the instrument , together with the patient 's own quality of life . This study demonstrated that convergence was valid : Pearson 's correlation coefficients between clinical score differences and quality of life score differences were small ( from 0.199–0.564 ) but were statistically different from 0 ( p<0.001 ) . St and ardized response mean ( SRM ) and effect size ( ES ) were calculated to assess sensitivity to change . SRM and ES both demonstrated considerble responsiveness to change ( > 0.80 ) . Reliability , face , content , construct validity and responsiveness were also determined for this specific quality of life question naire relating to venous insufficiency . Results suggest that this question naire may be used with confidence to assess quality of life in clinical trials on chronic venous insufficiency STUDY OBJECTIVE : To determine the prevalence of varicose veins and chronic venous insufficiency ( CVI ) in the general population . DESIGN : Cross sectional survey . SETTING : City of Edinburgh . PARTICIPANTS : Men and women aged 18 - 64 years selected r and omly from age-sex registers of 12 general practice s. MAIN RESULTS : In 1566 subjects examined , the age adjusted prevalence of trunk varices was 40 % in men and 32 % in women ( p < or = 0.01 ) . This sex difference was mostly a result of higher prevalence of mild trunk varices in men . More than 80 % of all subjects had mild hyphenweb and reticular varices . The age adjusted prevalence of CVI was 9 % in men and 7 % in women ( p < or = 0.05 ) . The prevalence of all categories of varices and of CVI increased with age ( p < or = 0.001 ) . No relation was found with social class . CONCLUSIONS : Approximately one third of men and women aged 18 - 64 years had trunk varices . In contrast with the findings in most previous studies , mainly conducted in the 1960s and 1970s , chronic venous insufficiency and mild varicose veins were more common in men than women . No evidence of bias in the study was found to account for this sex difference . Changes in lifestyle or other factors might be contributing to an alteration in the epidemiology of venous disease AIM Epidemiological data show that st and ard compression therapy for leg ulceration in chronic venous insufficiency ( CVI ) often fails to effectively improve patients ' condition . This study assesses the contribution of Daflon 500 mg added to conventional therapy in the healing of hypostatic ulcers of CVI patients . METHODS Patients of about 65 years were included , with ulcers > or = 2 and > or = 10 cm diameter on 1 or 2 limbs , Doppler ankle/arm pressure index > 0.9 , and no recent history of skin graft . Controls ( n=68 ) remained on compression alone while the tested group ( n=82 ) also received Daflon 500 mg 2 tablets/day during 6 months . Treatment could be stopped as soon as the reference ulcer appeared fully healed . Primary endpoints were the rate of healed ulcers and the time to complete healing assessed by planimetry/photography and clinical examination . Variations of the ulcer surface , appearance of the skin , and clinical symptoms of CVI were the secondary criteria . RESULTS Only 7 % of Daflon 500 mg patients necessitated the full 6 month therapy . Whatever the lesion size , from W8 significantly more healed ulcers were observed under Daflon 500 mg ( p=0.004 ) , and the ulcer surface was more reduced ( p=0.012 ) . For large ulcers , the rate of healing was approximately 2-fold higher with Daflon 500 mg , and the percentage of ulcers healed before W24 was significantly higher ( p=0.008 ) . Heavy leg sensation was significantly improved by Daflon 500 mg from W4 ( p < 0.05 ) . No treatment-related side effects were reported and the acceptability was considered excellent by 85 % of Daflon 500 mg patients . CONCLUSION Six months of Daflon 500 mg in addition to compression significantly improve some clinical symptoms and accelerate the healing process in patients with ulcerous complications of CVI , with a good acceptability AIM The Vein Consult Program is an international , observational , prospect i ve survey aim ing to collect global epidemiological data on chronic venous disorders ( CVD ) based on the CEAP classification , and to identify CVD management worldwide . The survey was organized within the framework of ordinary consultations , with general practitioners ( GPs ) properly trained on the use of the CEAP classification . METHODS Screening for CVD was to be performed by enrolling in the survey all consecutive out patients > 18 years whatever the reason for consultation , to record patient 's data and classify them according to the CEAP , from the stage C0s to C6 . The program enrolled 6232 GPs 91545 subjects were analysed . Their mean age was 50.6±16.9 years , younger patients being in the Middle East and older ones in Europe , and the proportion of women was higher than that of men . RESULTS The worldwide prevalence of CVD was 83.6 % : 63.9 % of the subjects ranging C1 to C6 , and 19.7 % being C0s subjects . C0s patients were more frequently men whatever the age and the geographical zone . C1-C3 appeared to be more frequent among women whatever the country but the rate of severe stages ( C4-C6 ) did not differ between men and women . GPs consider CVD subjects as patients eligible to specialist referral beginning from C2 but some geographical disparities were observed . CONCLUSION The VCP survey provides reliable results on CVD global epidemiology and shows that CVD affects a significant part of the population s worldwide , underlining the importance of adequate screening for CVD and training of both GPs and specialist physicians The objective of this study was to evaluate the efficacy of Daflon ® 500 mg ( Dios ) * in venous ulcers . A multicenter , double-blind , r and omized , controlled versus placebo ( Plac ) trial was conducted , with stratification according to the size of ulcer ( ≤ 10 cm and > 10 cm ) . The protocol called for a two-month treatment with Dios ( one tablet = 450 mg micronized purified Diosmin ) or a placebo , two tablets/day , in addition to compression therapy . Evaluations were performed every fifteen days , from DO to D60 . The primary endpoint , in accordance with Alex and er House group requirements were : percentage of patients with complete ulcer healing , ie , comparison between Dios and Plac group at D60 , and comparison of survival curves in each group between DO and D60 ( log rank test ) . Secondary endpoints included ulcer surface area assessed by computerized plani metric measurements , qualitative evaluation of ulcers , and symptoms . The patients were 105 men and women ranging in age from eighteen to eighty-five years , with st and ard compression stocking , who were undergoing st and ardized local care of ulcer and had no significant arterial disease ( ankle/arm systolic pressure index > 0.8 ) . Fifty-three patients received Dios , and 52 received Plac . The 2 groups were well matched for age ( m ±1 SD = seventy-one ±eleven years ) , gender , ulcer size , and associated disorders . Among patients with ulcer size ≤ 10 cm ( Dios = 44 , Plac = 47 ) a significantly larger number of patients had a complete ulcer healing at two months in the Dios group ( n = 14 ) in comparison with the Plac group ( n = 6 ) ( 32 % vs 13 % , P = 0.028 ) with a signifi cantly shorter time duration of healing ( P = 0.037 ) . No difference was shown for the secondary criteria , except for sensation of heavy legs ( P = 0.039 ) and a less atonic aspect of ulcer ( P = 0.030 ) in favor of Dios . Among the 14 patients with ulcer size > 10 cm ( Dios = 9 , Plac = 5 ) , subjected to a descriptive analysis only , no ulcer healed . This study showed that a two-month course of Daflon 500 mg at a daily dose of two tablets , in addition to conventional treatment , is of benefit in patients with venous ulcer ≤ 10 cm by accelerating complete healing OBJECTIVE to evaluate the efficacy of a micronised purified flavonoid fraction ( MPFF ) in the treatment of chronic venous disease ( CVD ) . DESIGN prospect i ve double blind , r and omised , control study . PATIENTS AND METHODS one hundred and one patients with symptomatic CVD were r and omly allocated to treatment for 60 days with either MPFF ( 51 patients ) or placebo ( 50 patients ) 500 mg twice daily . There were 28 men and 73 women , aged 22 - 65 years ( mean age 48 years ) . No difference regarding age , gender , clinical class or duration of symptoms was recorded between the treatment and placebo groups . A global score for evaluation of symptoms was used . Patients were investigated with plethysmography ( foot-volumetry ) and duplex-ultrasonography before and after the treatment period . For statistical comparison Cochran-Mantel-Haenszel test , two-sided Student t-test and covariance analysis were used and p<0.05 was regarded significant . RESULTS improvement of the global score of symptoms was reported by 21 patients in the MPFF group and by 16 in the placebo group ( N.S. ) . For the whole groups , no significant differences were recorded before and after treatment regarding foot-volumetric or ultrasonographic parameters . On the other h and , in patients with edema ( 20 in the MPFF group , 23 in the placebo group ) ultrasonographic reflux time was significantly reduced for those in the treatment group ( p=0.03 ) . This finding did not correlate to clinical symptoms . CONCLUSION in this study , MPFF did not change the symptoms of CVD , except night cramps . A secondary finding was reduced reflux times in patients with oedema , although no ultrasonographic or foot-volumetric parameters changed significantly for the whole group . The role of MPFF in treatment of patients with CVD needs to be further analysed in a large population Chronic venous insufficiency ( CVI ) of the lower limbs is a complex and fluctuating disease by its pathogenic mechanisms and its clinical symptoms . Although symptoms are subjective , they affect the quality of life and socio-professional activity of many patients . This is why convincing demonstration of therapeutic activity of a venotropic drug should be carried out according to strict methodology . Only r and omized double-blind controlled trials versus placebo ( no reference drugs being available ) could demonstrate the activity on condition that they are set up in a protocol , the statistical design of which , is adapted and defined " a priori " . Inclusion , non inclusion and judgement criteria must be rigorous , taking into account many exogenous and endogenous factors which could have influence on the severity or the change in CVI and on the comparability of groups at the beginning and at the end of the study . Thus , the main risk factors of CVI ( heredity , obesity , obstetrical and gynecological history , estroprogestogen treatment , profession , environment , etc . ) and the season when the patient is recruited should be taken into account . With respect to all these restraints on methodology , the venotrotopic activity of a flavonoid Daflon 500 mg ( 2 tablets daily ) was demonstrated in 200 patients ( 174 women , 26 men ) with organic CVI ( n = 83 ) or functional CVI ( n = 117 ) treated for two months in two double-blind r and omized trials versus placebo . The venotropic activity of Daflon 500 mg , was shown by a significant reduction of CVI signs and symptoms , whether organic or functional , and a significant improvement in venous hemodynamics according to plethysmographic parameters . Good acceptability was observed after medium and long term trials OBJECTIVE To assess the efficacy of a micronized purified flavonoid fraction ( Daflon 500 mg = Dios ) in venous leg ulcer healing , in addition to compression therapy and st and ardized local care . DESIGN Double-blind , multicentre , r and omized , parallel groups , controlled versus placebo trial ; stratification according to ulcer size . SUBJECTS 107 patients , with venous ulcer of the leg for at least 3 months , and accepting b and aging therapy . RESULTS 105 patients ( Dios = 53 , placebo = 52 ) were available for an intention to treat ( ITT ) analysis . Age ( mean + /- SD , 71+/-11 years ) , gender ( M = 33 , F = 74 ) and ulcer size were evenly distributed among both groups . 99 patients completed the protocol ( Dios = 51 , placebo = 48 ) . Among the 91 patients with ulcer size < or = 100 cm ( Dios = 44 , placebo = 47 ) , a significantly higher number of patients had complete ulcer healing at 2 months in the Dios group ( n = 14 ) in comparison to the placebo group ( n = 6 ) after ITT analysis ( 32 vs. 13 % , p = 0.028 ) and after per protocol analysis ( 32 vs. 14 % , p = 0.048 ) , and a shorter time duration of healing ( p = 0.037 ) . Among the 14 patients with ulcer size > 10 cm ( Dios = 9 , placebo = 5 ) , no ulcer healed . CONCLUSION This study showed that a 2-month course of purified micronized flavonoid fraction ( 2 tablets/day ) , in addition to conventional treatment , is of benefit in patients by accelerating complete healing of venous leg ulcers which are < or = 10 cm in diameter In 3 controlled clinical trials , double blind versus placebo , the activity of Daflon 500 mg , a new micronised flavonoid fraction , has been evaluated on venous tone using venous plethysmography . A double-blind , r and omized cross-over Phase II pharmaco- clinical trial has shown that Daflon 500 mg is statistically more effective than placebo on pathological legs , as well as normal legs . In this study , which included 20 patients suffering from post-thrombotic syndrome , Daflon 500 mg decreased : 1 ) venous capacity ( p less than 0.001 ) ; 2 ) venous distensibility ( p less than 0.001 ) ; 3 ) venous outflow time , measured by the two parameters total emptying venous time ( p less than 0.001 ) and T2p ( p less than 0.001 ) . These modifications have been observed 2 hours after administration without any significant change in T50 outflow , cardiad index , capillary filtration index , blood pressure , cardiac or respiratory rate . The same acute effect of increasing venous tone has been demonstrated in another pharmaco clinical trial , 1 and 2 hours after ingestion in 3 groups of 10 women suffering from venous insufficiency : group I without varicose , group II during pregnancy and group III with a post-thrombotic syndrome . Finally , in a Phase III clinical trial , in 2 parallel groups of 20 patients each with functional chronic venous insufficiency , Daflon 500 mg has been compared to placebo . It was then demonstrated after 1 and 2 months treatment an improvement in the functional symptoms and edema accompanied by a statistically significant increase of the venous tone . ( ABSTRACT TRUNCATED AT 250 WORDS AIM to study the effect on plasma vascular endothelial growth factor ( VEGF ) levels of oral purified flavonoid fraction treatment for sixty days in patients with chronic venous disease ( CVD ) . MATERIAL AND METHODS twenty patients < < CEAP > > ( clinical stage 2 - 4 ) with chronic venous disease were included . Duplex ultrasonography was used to assess the venous disease . Patients were treated for 60 days with Daflon(R ) 500 mg twice daily . Blood was collected from a foot vein immediately before starting treatment and within one week of stopping treatment . Plasma VEGF levels were determined using a s and wich ELISA method . RESULTS VEGF levels decreased in patients with stage C4 CVD after treatment with purified micronised flavonoid fraction treatment ( 98 pg/ml to 57 pg/ml ) . The levels of VEGF in patients with skin changes were significantly higher ( 98 pg/ml ) than those with normal skin ( 9 pg/ml p=<0.001 Wilcoxon ) . CONCLUSIONS plasma VEGF levels were much higher in patients who have skin changes of CVD . Plasma VEGF protein decreases in patients with CVD-induced dermatologic changes following treatment with purified micronised flavonoid fraction OBJECTIVES Leukocyte trapping due to leukocyte-endothelial activation has been implicated as the cause of lipodermatosclerosis and ulceration in patients with chronic venous disease . We investigated endothelial activity in normal controls and patients subjected to short-term venous hypertension . METHODS Twenty-five normal volunteers and 30 patients with chronic venous disease divided into two groups : varicose veins with skin changes ( LDS , n = 15 ) ; and varicose veins without skin changes ( VVs , n = 15 ) were studied . Blood sample s were taken from a foot vein before and after experimental venous hypertension . Plasma levels of ELAM-1 ( endothelial leukocyte adhesion molecule-1 ) , ICAM-1 ( intercellular adhesion molecule-1 ) , VCAM-1 ( vascular cell adhesion molecule-1 ) , and von Willebr and factor ( vWf ) was measured by an ELISA . RESULTS There was a significant rise in the plasma concentration of ELAM-1 , ICAM-1 and VCAM-1 in patients and normal controls in response to venous hypertension . Basal levels of plasma VCAM-1 and vWf were higher in patients with LDS compared to patients with VVs . The magnitude of rise of VCAM-1 was greater in patients with LDS compared to patients with VVs ( p = 0.01 , Mann-Whitney U-test ) . There was no difference in the basal levels or in the magnitude of change in plasma ICAM-1 and ELAM-1 between the two patient groups . CONCLUSION Venous hypertension results in endothelial activation which may aid endothelial-leukocyte adhesion . Patients with LDS exhibit increased VCAM-1 , which is a counterlig and for receptors expressed by monocytes and lymphocytes signifying that these cells may be more important in the development of skin changes The RELIEF study ( Reflux assEssment and quality of life improvement with micronized Flavonoids in chronic venous insufficiency [ CVI ] ) is a prospect i ve , controlled , multicenter , international study performed in patients with or without venous reflux . This study was conducted between March 1997 and December 1998 in 23 countries worldwide with the participation of more than 10,000 patients suffering from CVI . The European countries , the subject of this report , were represented by the Czech and Slovak Republics , Hungary , Pol and , Russia , and Spain . The principal aims of the study were : 1 . To vali date the first quality -of-life scale specific to chronic venous insufficiency ( CMVIQ ) in different language s and to assess the evolution of quality of life in patients suffering from CVI , with or without venous reflux , treated with micronized purified flavonoid fraction ( MPFF * ) ( 1,000 mg/day ) . 2 . To collect international epidemiologic data on venous reflux assessed with pocket Doppler and photoplethysmography . 3 . To assess the evolution of symptoms and signs with a specific emphasis on edema through vali date d Leg-O-Meter measurement ( heaviness , pain , cramps , sensation of swelling , edema ) in patients suffering from CVI and treated with MPFF , 1,000 mg/day , during 6 months . The first country-by-country statistical analysis and the European consoli date d analysis are now available . The CIVIQ question naires adapted to each participating country have been vali date d with highly significant validity and reproducibility ( p<0.0001 ) . All dimensions have demonstrated a highly significant and evolving improvement during the study . The results show several interesting findings concerning the epidemiologic data and , of these , two were particularly interesting : - More than 50 % of patients suffering from CVI ( class 0 to 4 of the CEAP classification ) were reflux-free , which means that they were suffering from functional CVI . Patient distribution between the different classes of the CEAP classification changed in a statistically significant manner after 6 months ' treatment with MPFF ; the number of patients in the more severe classes decreased to the benefit of the less severe classes . Symptoms such as pain , leg heaviness , sensation of swelling , and cramps were significantly improved ( p=0.0001 ) . This was associated with a significant decrease in edema , when present , measured by leg circumferences with the Leg-O-Meter ( p=0.0001 ) . In conclusion , the European results of the RELIEF study showed the perfect validity and reproducibility of CIVIQ question naire adaptations , and the positive progression of quality -of-life scores on MPFF treatment . This progression was paralleled by clinical improvement of patients reflected not only by assessment of CVI symptoms and signs but also by evolution of the CEAP classification A double-blind , placebo-controlled trial was carried out to assess the effectiveness of a new synthetic bioflavonoid , hidrosmin , in patients with chronic venous insufficiency of the lower limbs . Fifty-seven patients , showing varicose veins and ankle swelling and suffering from local pain and heaviness of the legs , were allocated at r and om to receive treatment for 45 days with 1 capsule 3-times daily of either 200 mg hidrosmin ( 30 patients ) or placebo ( 27 patients ) . Pain and heavy legs were assessed using rating scales ; swelling was assessed by a photographic method . The results showed that hidrosmin produced a significant clinical improvement in all of the parameters evaluated ; compared with placebo , there was a marked reduction in the main subjective symptoms accompanied by a 10 % reduction in swelling . Apart from 1 patient who complained of epigastric pain , there were no reports of adverse events during the study period AIM The aim was to investigate the effect of micronized purified flavonoid fraction ( MPFF ; Daflon ® 500 mg , Laboratoires Servier , France ) versus placebo , on pain and quality of life ( QoL ) in patients with symptomatic chronic venous disease ( CVD ) . METHODS A large r and omized , double-blind , placebo-controlled , parallel-group study was conducted to evaluate treatment effects on vesperal oedema using water displacement volumetry ( WDV ) . Other criteria were leg pain\heaviness assessed by Visual Analog Scale ( VAS ) and Quality Of Life Question naire ( CIVIQ-20 ) . Study treatments were administered once a day for 4 months . The tolerance to the study treatments was assessed based on spontaneously reported adverse events , coded using the MedDRA dictionary . The present post-hoc analysis focuses on the subgroup of symptomatic patients having a baseline VAS>4 cm . RESULTS The main study included 1137 patients classified C3 or C4 according to CEAP classification , with 592 in the symptomatic subgroup : 296 r and omized to MPFF and 296 to placebo . Patient demographics and medical history were well-balanced at baseline . The main study was inconclusive on WDV for method ological reasons . In the symptomatic subgroup , MPFF treatment was associated with a greater reduction in VAS score than on placebo treatment ( between-group difference = -0.5 cm ; P=0.031 ) and greater improvement in CIVIQ score ( between-group difference = 3.1 % ; P=0.040 ) . CONCLUSION A 4-month treatment with MPFF significantly reduced leg pain/heaviness and improved QOL when compared to placebo and was well tolerated OBJECTIVES The goals of this study were to document the prevalence of varicose veins , skin trophic changes , and venous symptoms in a sample of the general population of France , to document their main risk factors , and to assess relationships between them . METHODS This cross-sectional epidemiologic study was carried out in the general population of 4 locations in France : Tarentaise , Grenoble , Nyons , and Toulon . R and om sample s of 2000 subjects per location were interviewed by telephone , and a sub- sample of subjects completed medical interviews and underwent physical examination , and the presence of varicose veins , trophic changes , and venous symptoms was recorded . RESULTS Prevalence of varicose veins , skin trophic changes , and venous symptoms was not statistically different in the 4 locations . In contrast , sex-related differences were found : varicose veins were found in 50.5 % of women versus 30.1 % of men ( P < .001 ) ; trophic skin changes were found in 2.8 % of women versus 5.4 % of men ( P = NS ) , and venous symptoms were found in 51.3 % of women 51.3 % versus 20.4 % of men ( P < .001 ) . Main risk factors for varicose veins were age and family history in both sexes , and pregnancy in women . Female sex was a significant factor only for non-saphenous varicose veins . Varicose veins , age , and pitting edema were the most significant risk factors for trophic skin changes . The risk factors for venous symptoms were female sex , varicose veins , and prolonged sitting or st and ing . A negative relationship with age was found in women . CONCLUSION Our results show a high prevalence of chronic venous disorders of the lower limbs in the general population of France , with no significant geographic variations . They also provide interesting insights regarding the association of varicose veins , skin trophic changes , and venous symptoms Venous leg ulcers ( VLUs ) affect millions of patients worldwide and are a tremendous financial burden on our health care system . The hallmark of venous disease of the lower extremities is venous hypertension , and compression is the current mainstay of treatment . However , many patients are non-compliant , partly because of the complexity of the dressings and the difficulties with application and removal . The aim of our study was to test an effective compression dressing regimen for patients with VLUs who require changing the ulcer primary dressing twice daily . We used two layers of a latex-free tubular elastic b and age for compression . The primary endpoint of our study was increased wound-healing rate and our secondary endpoint was complete wound closure . All active study subjects had positive healing rates at week 4 and week 8 . Two subjects achieved complete wound closure by week 8 . We conclude that compression with a latex-free tubular elastic b and age can be safely used in patients with VLUs requiring frequent dressing changes . This type of compression allows for daily inspection of wounds , dressing changes at home , flexibility in the context of clinical trials , and is a compromise for patients who are intolerant to compression dressings |
12,464 | 21,182,379 | The effectiveness of JCs in supporting evidence -based decision making is not clear . | BACKGROUND Journal clubs ( JCs ) are a common form of interactive education in health care aim ing to promote the uptake of research evidence into practice , but their effectiveness has not been established .
OBJECTIVE This systematic review aim ed to determine whether the JC is an effective intervention in supporting clinical decision making . | OBJECTIVES : Several studies have evaluated whether evidence -based medicine ( EBM ) training courses can improve skills such as literature search ing and critical appraisal but to date , few data exist on whether teaching EBM skills and providing evidence -based re sources result in change in behavior or clinical outcomes . This study was conducted to evaluate whether a multifaceted EBM intervention consisting of teaching EBM skills and provision of electronic evidence re sources changed clinical practice . DESIGN : Before/after study . SETTING : The medical inpatient units at a district general hospital . PARTICIPANTS : Thirty-five attending physicians and 12 medicine residents . INTERVENTION : A multicomponent EBM intervention was provided including an EBM training course of seven 1-hour sessions , an EBM syllabus and textbook , and provision of evidence -based re sources on the hospital network . MEASUREMENTS AND MAIN RESULTS : The primary outcome of the study was the quality of evidence in support of therapies initiated for the primary diagnoses in 483 consecutive patients admitted during the month before and the month after the intervention . Patients admitted after implementation of the EBM intervention were significantly more likely to receive therapies proven to be beneficial in r and omized controlled trials ( 62 % vs 49 % ; P=.016 ) . Of these trial-proven therapies , those offered after the EBM intervention were significantly more likely to be based on high- quality r and omized controlled trials ( 95 % vs 87 % ; P=.023 ) . CONCLUSIONS : A multifaceted intervention design ed to teach and support EBM significantly improved evidence -based practice patterns in a district general hospital This critical review examines the efficacy of communication interventions for improving communication outcomes in adolescents with acquired brain injury . Five articles were included in this review . Studies included four Level 1 design s ( i.e. , one r and omized controlled trial ( RCT ) , one single subject crossover design , one single subject multiple baseline design , one single subject design ) , and one Level 3 design ( i.e. , single group preposttest design ) . Overall , the results of this review revealed suggestive evidence that communication interventions are effective at improving communication outcomes for adolescents with acquired brain injury . Clinical implication s and future research recommendations are also discussed Objective To determine whether fellowship training in critical care medicine with critical appraisal exercises improves the ability and confidence of fellows to evaluate the medical literature . Design Prospect i ve , interventional pilot study . Setting Multidisciplinary critical care medicine training program at a large university hospital . InterventionFellows were given three didactic sessions covering study design , analysis , and critical appraisal techniques . During the course of the year , each fellow was required to review one article from the literature and present a critique of this article to the group and faculty ( Journal Club ) . Fellows were guided in the preparation of this presentation by one of the critical care medicine faculty . Finally , a written analysis and critique of the article was performed by each fellow . Measurements and Main Results A test was given to each fellow at the beginning and end of the academic year . This test consisted of two pairs of articles on therapy for acute lung injury . For the pretest , each fellow was assigned , at r and om , one pair of articles . Fellows were given 1 hr to review both articles and to fill out a six-point test to assess their ability and confidence to appraise each article . At the end of the year , each fellow was tested on the opposite pair , the tests were grade d in a blinded fashion and the results of each test were compared . Six fellows completed both pre- and posttests . These paired results were analyzed separately , whereas results for another six fellows were conducted as an unpaired analysis . Mean scores increased both for the paired analysis ( 4.1 ± 0.7 vs. 5.1 ± 0.5;p = .015 ) and for the unpaired analysis ( 4.3 ± 0.6 vs. 5.0 ± 0.5;p = .012 ) . Self-reported confidence in critical appraisal also increased ( 2.5 ± 0.5 vs. 3.9 ± 0.7;p = .004 and 2.6 ± 0.5 vs. 3.9 ± 0.6;p < .001 , respectively ) . Conclusion Critical appraisal exercises used in the training of critical care medicine fellows appear to improve both ability and confidence to appraise relevant medical literature Background Attitudes and barriers to implementing EBM have been examined extensively , but scant evidence exists regarding the impact of EBM teaching on primary care physicians ’ point of care behavior . Objective Gaining insight into behavioral and attitudinal changes of facilitators and participants during a multifaceted EBM educational intervention . Design , setting , and participants A qualitative study on primary care physicians and facilitators from a large HMO selected from the intervention arm of a parallel controlled trial using purpose ful sampling . We conducted focus groups with 13 facilitators and 17 physicians and semi-structured interviews with 10 facilitators and 11 physicians . Results Both facilitators and participants believed EBM enhanced the quality of their practice . The intervention affected attitudes and knowledge , but had little impact on physicians ’ ability to utilize pre-appraised re sources at the point of care . Using EBM re sources during consultation was perceived to be a complex task and impractical in a busy setting . Conversely , a positive impact on using medication data bases was noted . Medication data bases were perceived as easy to use during consultations in which the benefits outweighed the barriers . The intervention prompted physicians to write down clinical questions more frequently and to search for answers at home . Conclusions This study underlines the need not only to enhance EBM skills , but also to improve the ease of use of EBM re sources at the point of care . Tasks should be simplified by tailoring evidence -based information retrieval systems to the busy clinical schedule . Participants ’ recommendations to establish an HMO decision support service should be considered STUDY OBJECTIVES To compare the performance of an evidence -based medicine ( EBM ) approach and a traditional approach to teaching critical appraisal skills to emergency medicine residents . METHODS This was a prospect i ve , case-controlled trial of 32 emergency medicine residents ( 16 control and 16 intervention ) . Intervention residents were exposed to a monthly , 1-hour journal club using an EBM approach to critical appraisal over the course of 1 year . Control residents were exposed to a traditional , unstructured journal club , also monthly . Both groups were given a factitious article to evaluate in an essay format before and after the 12-month study period . The Wilcoxon rank sum test was used to compare mean improvement in test scores for each group . RESULTS The mean improvement in test scores was 1.80 for the control group and 1.53 for the intervention group ; these values were not significantly different ( P = .90 ) . The difference in mean change in test score between the 2 groups was.27 points . CONCLUSION Compared with a traditional approach , an EBM approach to teaching critical appraisal did not appear to improve the critical appraisal skills of emergency medicine residents . However , because of the small number of subjects studied , small differences in critical appraisal skill improvement can not be ruled out OBJECTIVE To investigate whether a limited teaching intervention , based on principles of adult education , could change residents ' literature reading attitudes , behaviors , and knowledge . DESIGN The educational intervention supplemented an ongoing bimonthly journal club . The effects on residents were studied prospect ively before and four months following the intervention . SETTING A community hospital internal medicine training program . PARTICIPANTS All 14 residents : six in the first year , and four each in the second and third years of training . INTERVENTION A one-hour seminar incorporating principles of adult education , including the use of multiple teaching modalities . The content was based on the critical literature reading guidelines published by the McMaster group . Reinforcement of learning objectives was achieved by learner participation , written assignments , active feedback , and follow-up in subsequent journal clubs . RESULTS Residents improved their performances on objective testing of critical appraisal knowledge by 60 % ( p = 0.02 ) . They reported improved ability to appraise original research articles critically ( p = 0.01 ) and reported spending more useful time reading . Unaffected were the total time spent reading journals , the reasons for reading them , and the perceived value of journals in " keeping up " with advances in medical knowledge . CONCLUSION Journal clubs are important to residents , and their effectiveness in teaching critical appraisal and promoting reading of the literature may be augmented by applying principles of adult education BACKGROUND We performed a prospect i ve controlled trial of a monthly journal club to determine if it would increase pediatric residents ' knowledge of clinical epidemiology and biostatistics . METHODS Intervention residents received two didactic sessions before the journal club started . Eight monthly journal club sessions followed . Pediatric residents at another institution served as controls . Intervention and control residents completed a pre- and post-test on clinical epidemiology and biostatistics . RESULTS Neither the intervention nor the control group showed a significant change in test scores over the 9-month period . CONCLUSION A more intensive and more structured approach is needed to effectively teach clinical epidemiology and biostatistics to residents Background A discipline which critically looks at the evidence for practice should itself be critically examined . Credible evidence for the effectiveness of training in evidence -based healthcare ( EBHC ) is essential . We attempted to summarise the current knowledge on evaluating the effectiveness of training in EBHC while identifying the gaps . Methods A working group of EBHC teachers developed a conceptual framework of key areas of EBHC teaching and practice in need of evidence mapped to appropriate methods and outcomes . A literature search was conducted to review the current state of research in these key areas . Studies of training interventions that evaluated effectiveness by considering learner , patient or health system outcomes in terms of knowledge , skills , attitude , judgement , competence , decision-making , patient satisfaction , quality of life , clinical indicators or cost were included . There was no language restriction . Results Of 55 articles review ed , 15 met the inclusion criteria : six systematic review s , three r and omised controlled trials and six before-after studies . We found weak indications that undergraduate training in EBHC improves knowledge but not skills , and that clinical ly integrated postgraduate teaching improves both knowledge and skills . Two r and omised controlled trials reported no impact on attitudes or behaviour . One before-after study found a positive impact on decision-making , while another suggested change in learners ' behaviour and improved patient outcome . We found no studies assessing the impact of EBHC training on patient satisfaction , health-related quality of life , cost or population -level indicators of health . Conclusions Literature evaluating the effectiveness of training in EBHC has focused on short-term acquisition of knowledge and skills . Evaluation design s were method ologically weak , controlled trials appeared inadequately powered and systematic review s could not provide conclusive evidence owing to weakness of study design An investigation was made as to whether studies have found journal clubs for physicians in training to be effective for improving patient . care , teaching critical appraisal skills , improving reading habits , increasing knowledge of clinical epidemiology and biostatistics , and increasing the use of medical literature in clinical practice . A literature search was undertaken using 10 data bases and retrieval systems and h and search es of journals , conference proceedings and personal files . The rigor of studies meeting the inclusion criteria was analyzed using a protocol based on methods established by the Cochrane Collaboration . One r and omized controlled trial found an improvement in knowledge of clinical epidemiology and biostaristics , reading habits , and the use of medical literature in practice , but no improvement in critical appraisal skills . Six less method ologically rigorous studies found possible improvement in critical appraisal skills . It is concluded that journal clubs may improve knowledge of clinical epidemiology and biostatistics , reading habits , and the use of medical literature in practice . A multi-center , r and omized controlled trial of journal clubs is needed to assess whether journal clubs improve critical appraisal skills This study sought to identify the attitudes of family practice residents toward journal clubs and the effect that preparing a journal club session has on the resident 's view of the medical literature . Residents from Valley Medical Center were prospect ively assessed over a three-year period . Residents selected the improvement of critical appraisal skills as the most important journal club goal . However , they reported that their journal club experiences did not improve their opinions of the journals selected . The results are discussed in the context of recent trends in journal clubs OBJECTIVE To determine the effectiveness of different types of interventions in improving health professional performance and health outcomes . DATA SOURCES MEDLINE , SCI SEARCH , CINAHL and the Research and Development Re source Base in CME were search ed for trials of educational interventions in the health care professions published between 1970 and 1993 inclusive . STUDY SELECTION Studies were selected if they provided objective measurements of health professional performance or health outcomes and employed r and om or quasi-r and om allocation methods in their study design s to assign individual subjects or groups . Interventions included such activities as conferences , outreach visits , the use of local opinion leaders , audit and feedback , and reminder systems . DATA EXTRACTION Details extracted from the studies included the study design ; the unit of allocation ( e.g. , patient , provider , practice , hospital ) ; the characteristics of the targeted health care professionals , educational interventions and patients ( when appropriate ) ; and the main outcome measure . DATA SYNTHESIS The inclusion criteria were met by 102 trials . Areas of behaviour change included general patient management , preventive services , prescribing practice s , treatment of specific conditions such as hypertension or diabetes , and diagnostic service or hospital utilization . Dissemination-only strategies , such as conferences or the mailing of unsolicited material s , demonstrated little or no changes in health professional behaviour or health outcome when used alone . More complex interventions , such as the use of outreach visits or local opinion leaders , ranged from ineffective to highly effective but were most often moderately effective ( result ing in reductions of 20 % to 50 % in the incidence of inappropriate performance ) . CONCLUSION There are no " magic bullets " for improving the quality of health care , but there are a wide range of interventions available that , if used appropriately , could lead to important improvements in professional practice and patient outcomes The journal club is an established teaching modality in many house-staff training programs . To determine if a journal club improves house-staff reading habits , knowledge of epidemiology and biostatistics , and critical appraisal skills , we r and omized 44 medical interns to receive either a journal club or a control seminar series . A test instrument developed by the Delphi method was administered before and after the interventions ( mean , five journal club sessions ) . By self-report , 86 % of the house staff in the journal club group improved their reading habits vs 0 % in the control group . Knowledge scores increased more in the journal club group than in the control group , and a trend was found toward more knowledge gained as more sessions were attended . Ability to appraise critically a test article increased slightly in each group , but there was no significant difference between the groups . We conclude that a journal club is a powerful motivator of critical house-staff reading behavior and can help teach epidemiology and biostatistics to physicians-in-training |
12,465 | 28,707,202 | Although there was heterogeneity in the neuropsychological measures used to assess executive functioning , tests could be grouped into the subcomponents they assessed .
Inhibition appears relatively spared from the effects of chemotherapy , whereas impairments in shifting and updating are more commonly found following chemotherapy . | Purpose Women with breast cancer have reported adverse cognitive effects following chemotherapy .
Evidence is mixed on whether executive functioning is particularly impaired in women treated with chemotherapy , in part due to the wide range of tasks used to measure executive processes .
We performed a systematic review of the published literature to evaluate whether some subcomponents of executive functioning are more vulnerable to impairment than others among breast cancer survivors who had been treated with chemotherapy . | PURPOSE Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration . Whether chemotherapy has any long-term effects on cognition is largely unknown , yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the improved survival . We investigated whether cyclophosphamide , methotrexate , and fluorouracil ( CMF ) chemotherapy for breast cancer is associated with worse cognitive performance more than 20 years after treatment . PATIENTS AND METHODS This case-cohort study compared the cognitive performance of patients with breast cancer who had a history of adjuvant CMF chemotherapy treatment ( six cycles ; average time since treatment , 21 years ; n = 196 ) to that of a population -based sample of women never diagnosed with cancer ( n = 1,509 ) . Participants were between 50 and 80 years of age . Exclusion criteria were ever use of adjuvant endocrine therapy , secondary malignancy , recurrence , and /or metastasis . RESULTS The women exposed to chemotherapy performed significantly worse than the reference group on cognitive tests of immediate ( P = .015 ) and delayed verbal memory ( P = .002 ) , processing speed ( P < .001 ) , executive functioning ( P = .013 ) , and psychomotor speed ( P = .001 ) . They experienced fewer symptoms of depression ( P < .001 ) , yet had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance . CONCLUSION Survivors of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago perform worse , on average , than r and om population controls on neuropsychological tests . The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy . This study suggests that cognitive deficits following breast cancer diagnosis and subsequent CMF chemotherapy can be long lasting Background Cognitive problems in breast cancer patients are common after systemic treatment , particularly chemotherapy . An increasing number of fMRI studies show altered brain activation in breast cancer patients after treatment , suggestive of neurotoxicity . Previous prospect i ve fMRI studies administered a single cognitive task . The current study employed two task paradigms to evaluate whether treatment-induced changes depend on the probed cognitive domain . Methods Participants were breast cancer patients scheduled to receive systemic treatment ( anthracycline-based chemotherapy + /- endocrine treatment , n = 28 ) , or no systemic treatment ( n = 24 ) and no-cancer controls ( n = 31 ) . Assessment took place before adjuvant treatment and six months after chemotherapy , or at similar intervals . Blood oxygen level dependent ( BOLD ) activation and performance were measured during an executive functioning task and an episodic memory task . Group-by-time interactions were analyzed using a flexible factorial design . Results Task performance did not differ between patient groups and did not change over time . Breast cancer patients who received systemic treatment , however , showed increased parietal activation compared to baseline with increasing executive functioning task load compared to breast cancer patients who did not receive systemic treatment . This hyperactivation was accompanied by worse physical functioning , higher levels of fatigue and more cognitive complaints . In contrast , in breast cancer patients who did not receive systemic treatment , parietal activation normalized over time compared to the other two groups . Conclusions Parietal hyperactivation after systemic treatment in the context of stable levels of executive task performance is compatible with a compensatory processing account of hyperactivation or maintain adequate performance levels . This over-recruitment of brain regions depends on the probed cognitive domain and may represent a response to decreased neural integrity after systemic treatment . Overall these results suggest different neurobehavioral trajectories in breast cancer patients depending on treatment type Objective : To assess patterns of regional brain activation in response to varying working memory loads shortly after mild traumatic brain injury ( MTBI ) . Background : Many individuals complain of memory difficulty shortly after MTBI . Memory performance in these individuals can be normal despite these complaints . Methods : Brain activation patterns in response to a working memory task ( auditory n-back ) were assessed with functional MRI in 12 MTBI patients within 1 month of their injury and in 11 healthy control subjects . Results : Brain activation patterns differed between MTBI patients and control subjects in response to increasing working memory processing loads . Maximum intensity projections of statistical parametric maps in control subjects showed bifrontal and biparietal activation in response to a low processing load , with little additional increase in activation associated with the high load task . MTBI patients showed some activation during the low processing load task but significantly increased activation during the high load condition , particularly in the right parietal and right dorsolateral frontal regions . Task performance did not differ significantly between groups . Conclusion : MTBI patients differed from control subjects in activation pattern of working memory circuitry in response to different processing loads , despite similar task performance . This suggests that injury-related changes in ability to activate or to modulate working memory processing re sources may underlie some of the memory complaints after MTBI PURPOSE We previously evaluated fatigue , menopausal symptoms , and cognitive dysfunction in patients receiving adjuvant therapy for breast cancer and matched healthy women . Here we report assessment of these women 1 and 2 years later . PATIENTS AND METHODS Patients without relapse and controls were evaluated by the Functional Assessment of Cancer Treatment-General Quality of Life question naire , with subscales for fatigue and endocrine symptoms , and by the High Sensitivity Cognitive Screen . RESULTS There were 104 , 91 , and 83 patients and 102 , 81 , and 81 controls assessed at baseline and at 1 and 2 years , respectively . Median Functional Assessment of Cancer Treatment-Fatigue scores ( range , 0 to 52 ) for patients improved from 31 ( on chemotherapy ) to 43 and 45 at 1 and 2 years , respectively , but were stable in controls ( 46 to 48 ) . Median Functional Assessment of Cancer Treatment-Endocrine Symptoms scores ( range , 0 to 72 ) for patients improved from 57 ( on chemotherapy ) to 59 and 61 at 1 and 2 years , respectively , and were stable in controls ( 64 to 65 ) . Differences between patients and controls remained significant for these scales . The incidence of moderate-severe cognitive dysfunction by the High Sensitivity Cognitive Screen decreased in patients from 16 % ( on chemotherapy ) to 4.4 % and 3.8 % and in controls from 5 % to 3.6 % and 0 % at 1 and 2 years , respectively . There were minimal differences between estrogen receptor-positive patients who started hormonal therapy ( mainly tamoxifen ) after chemotherapy and estrogen receptor-negative patients who did not . Differences in quality of life between patients and controls were significant only at baseline . CONCLUSION Fatigue , menopausal symptoms , and cognitive dysfunction are important adverse effects of chemotherapy that improve in most patients . Hormonal treatment has minimal impact on them PURPOSE To examine the impact of age and cognitive reserve on cognitive functioning in patients with breast cancer who are receiving adjuvant treatments . PATIENTS AND METHODS Patients with breast cancer exposed to chemotherapy ( n = 60 ; mean age , 51.7 years ) were evaluated with a battery of neuropsychological and psychological tests before treatment and at 1 , 6 , and 18 months after treatment . Patients not exposed to chemotherapy ( n = 72 ; mean age , 56.6 years ) and healthy controls ( n = 45 ; mean age , 52.9 years ) were assessed at matched intervals . RESULTS Mixed-effects modeling revealed significant effects for the Processing Speed and Verbal Ability domains . For Processing Speed , a three-way interaction among treatment group , age , and baseline cognitive reserve ( P < .001 ) revealed that older patients with lower baseline cognitive reserve who were exposed to chemotherapy had lower performance on Processing Speed compared with patients not exposed to chemotherapy ( P = .003 ) and controls ( P < .001 ) . A significant group by time interaction for Verbal Ability ( P = .01 ) suggested that the healthy controls and no chemotherapy groups improved over time . The chemotherapy group failed to improve at 1 month after treatment but improved during the last two follow-up assessment s. Exploratory analyses suggested a negative effect of tamoxifen on Processing Speed ( P = .036 ) and Verbal Memory ( P = .05 ) in the no-chemotherapy group . CONCLUSION These data demonstrated that age and pretreatment cognitive reserve were related to post-treatment decline in Processing Speed in women exposed to chemotherapy and that chemotherapy had a short-term impact on Verbal Ability . Exploratory analysis of the impact of tamoxifen suggests that this pattern of results may be due to a combination of chemotherapy and tamoxifen PURPOSE To prospect ively examine alterations in working memory ( WM ) -associated brain activation related to breast cancer and treatment by using functional magnetic resonance imaging . PATIENTS AND METHODS Patients treated with chemotherapy ( CTx+ ; n = 16 ) or without chemotherapy ( CTx- ; n = 12 ) and healthy controls ( n = 15 ) were scanned during an n-back task at baseline ( after surgery but before radiation , chemotherapy , and /or antiestrogen treatment ) , 1 month after completion of chemotherapy ( M1 ) , and 1 year later ( Y1 ) , or at yoked intervals for CTx- and controls . SPM5 was used for all image analyses , which included cross-sectional between-group and group-by-time interaction and longitudinal within-group analyses , all using a statistical threshold of 0.001 . RESULTS At baseline , patients with cancer showed increased bifrontal and decreased left parietal activation compared with controls . At M1 , both cancer groups showed decreased frontal hyperactivation compared with controls , with increased hyperactivation at Y1 . These cross-sectional findings were confirmed by group-by-time interaction analyses , which showed frontal activation decreases from baseline to M1 in patients compared with controls . Within-group analyses showed different patterns of longitudinal activation change by treatment group ( CTx+ or CTx- ) , with prominent alterations in the frontal lobes bilaterally . CONCLUSION Significant frontal lobe hyperactivation to support WM was found in patients with breast cancer . Superimposed on this background , patients showed decreased frontal activation at M1 , with partial return to the previously abnormal baseline at Y1 . These functional changes correspond to frontal lobe regions where we previously reported structural changes in this cohort and provide prospect i ve , longitudinal data that further eluci date mechanisms underlying cognitive effects related to breast cancer and its treatment The aim of this study is to use functional magnetic resonance imaging ( fMRI ) to prospect ively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer . Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer . We hypothesized that pre-treatment factors , unrelated to chemotherapy per se , might increase vulnerability to post-treatment fatigue and cognitive dysfunction . Patients treated with ( n = 28 ) or without chemotherapy ( n = 37 ) and healthy controls ( n = 32 ) were scanned coincident with pre- and one-month post-chemotherapy during a verbal working memory task ( VWMT ) and assessed for fatigue , worry , and cognitive dysfunction . fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function . The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response , characterized by higher spatial variance in executive network activity , than the non-chemotherapy group . Also , the chemotherapy group reported greater post-treatment fatigue than the other groups . Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints , while treatment group , age , hemoglobin , worry , and mean executive network activity levels did not predict these outcomes . Pre-treatment neural inefficiency ( indexed by high spatial variance ) in the executive network , which supports attention and working memory , was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se . This executive network compromise could be a pre-treatment neuromarker of risk , indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction Adjuvant chemotherapy is associated with improvements in long-term cancer survival . However , reports of cognitive impairment following treatment emphasize the importance of underst and ing the long-term effects of chemotherapy on brain functioning . Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning . This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer . Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to underst and how brain networks support specific cognitive functions . Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging ( fMRI ) session before chemotherapy , 1 month after , and 1 year after the completion of chemotherapy . Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus ( IPS ) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex ( PCC ) to examine connectivity in the default mode network . Results showed decreased functional connectivity 1 month after chemotherapy that partially returned to baseline at 1 year in the dorsal attention network . Decreased connectivity was seen in the default mode network at 1 month and 1 year following chemotherapy . In addition , increased subjective memory complaints were noted at 1 month and 1 year post-chemotherapy . These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment In the present study , we sought to investigate which brain structures are recruited in planning tasks of increasing complexity . For this purpose , a parametric self-paced pseudo-r and omized event-related functional MRI version of the Tower of London task was design ed . We tested 22 healthy subjects , enabling assessment of imaging results at a second ( r and om effects ) level of analysis . Compared with baseline , planning activity was correlated with increased blood oxygenation level-dependent ( BOLD ) signal in the dorsolateral prefrontal cortex , striatum , premotor cortex , supplementary motor area , and visuospatial system ( precuneus and inferior parietal cortex ) . Task load was associated with increased activity in these same regions . In addition , increasing task complexity was correlated with activity in the left anterior prefrontal cortex , a region supposed to be specifically involved in third-order higher cognitive functioning Studies suggest that adjuvant chemotherapy for early stage breast cancer ( BC ) is associated with cognitive impairment related to attention , memory , and visuospatial functioning . However , other studies have failed to confirm that relationship . We report one of the first longitudinal , controlled studies of cognitive effects of chemotherapy in older post-menopausal women . Sixty-one post-menopausal women with non-metastatic BC were administered neuropsychological tests before adjuvant therapy ( Time1 ) , six months after treatment ( Time2 ) , and at a final 6-month follow-up ( Time3 ) . Thirty women were treated with chemotherapy ; thirty-one women who received no chemotherapy were controls . Cognitive domains measured included motor , language , attention/concentration/working memory , visuospatial , and memory ( verbal and visual ) . Time-by-treatment interaction was significant in the motor domain ( P = 0.007 ) with poorer performance in women treated with chemotherapy . For the other domains , scores did not significantly vary over time by group . In post-menopausal women , chemotherapy was not associated with changes in cognitive function in areas reported by BC survivors : attention , memory , and information processing . Motor slowing in women treated with chemotherapy could be secondary to peripheral neuropathy rather than an indication of more general declines in cognitive processing . Future studies should control for the independent effects of slowed motor functioning when looking to study possible chemotherapy related cognitive processing deficits OBJECTIVES To report on the longitudinal cognitive functioning of older women receiving adjuvant chemotherapy for breast cancer . DESIGN Neuropsychological and functional status testing were performed before chemotherapy and 6 months after chemotherapy . SETTING Cancer center . PARTICIPANTS Thirty-one patients aged 65 and older with Stage I to III breast cancer . Of the 31 patients enrolled , three refused post-testing , and 28 were evaluable . MEASUREMENTS The following domains of cognitive function were examined : attention ; verbal memory ; visual memory ; and verbal , spatial , psychomotor , and executive functions . RESULTS Participants had a mean age of 71 ( range 65 - 84 ) : 39 % Stage I , 50 % Stage II , and 11 % Stage III . The number of scores 2 st and ard deviations ( SDs ) below the norm were calculated for each patient before and 6 months after chemotherapy ; 14 ( 50 % ) had no change , 11 ( 39 % ) worsened , and three ( 11 % ) improved ( P=.05 ) . Seven patients ( 25 % ) experienced a decline in cognitive function , defined as a 1-SD decline from pre- to post-testing in two or more neuropsychological domains . Exploratory analyses revealed no significant difference between functional status , comorbidity , and depression scale scores and change in overall quality -of-life scores before and after chemotherapy . CONCLUSION In this cohort of older women receiving adjuvant chemotherapy , a subset experienced a decline in cognitive function from before chemotherapy to 6 months after chemotherapy . Further prospect i ve study is needed to confirm these observations and to identify the subgroup at special risk OBJECTIVE A number of cross-sectional studies have reported reduced cognitive function in cancer patients receiving chemotherapy compared with other cancer patients and healthy controls , suggesting that chemotherapy could be associated with cognitive side-effects . Recently published prospect i ve studies question this hypothesis , but it is still unclear whether cancer patients should regard cognitive problems as a potential risk when receiving chemotherapy . METHODS In the present study we examine whether cancer patients ( n=34 ) receiving chemotherapy differed in cognitive changes during treatment compared with cardiac patients ( n=12 ) and healthy controls ( n=12 ) tested at 3 - 4 months interval . RESULTS Our results showed no differences with respect to changes in cognitive performance over time between cancer patients in chemotherapy , cardiac patients , and healthy controls . In addition , the number of individuals showing reliable decline or improvement on cognitive tests did not differ between groups . CONCLUSION Taken together , our results do not support a hypothesis of cognitive side-effects of st and ard-dose chemotherapy in breast cancer patients It is believed widely that chemotherapy‐induced cognitive impairment occurs in a subgroup of patients with breast cancer . However , recent reports have provided no evidence that chemotherapy affects cognition . In this study , the authors question ed whether cognitive compromise in patients with breast cancer is attributable to chemotherapy . In addition , the effects of therapy‐induced menopause and of the erythropoiesis‐stimulating factor darbepoetin α on cognitive performance were assessed BACKGROUND Studies on cognitive functioning in breast cancer patients point out that a subset of women exhibit chemotherapy-related neuropsychological impairment . Thereby , high-dose therapy may elevate the risk of cognitive dysfunctions . The primary purpose of the study was to evaluate the impact of high-dose versus st and ard-dose chemotherapy on the late neuropsychological outcome in r and omized assigned high-risk breast cancer survivors . Next to focusing prevalence , function specificity and extent of cognitive impairment , the question as to whether doses-dependent group differences occur was investigated . PATIENTS AND METHODS Twenty-four high-dose and 23 st and ard-dose patients 5 years , on average , after treatment underwent a comprehensive neuropsychological assessment . In addition , 29 early-stage breast cancer patients matched for age , education and time since treatment were recruited as a comparison group . RESULTS Global cognitive impairment was observed in 8 % of high-dose versus 13 % of st and ard-dose compared with 3 % of early-stage breast cancer patients . Compared with normative data , all patient groups performed worse on one attention subtest measuring the simple reaction time ( P < 0.001 in each case ) . By contrast , no significant between-group differences on the late neuropsychological outcome were found . CONCLUSIONS Five years after treatment , st and ard-dose patients were slightly , but not significantly , more impaired in cognitive performance than high-dose patients BACKGROUND Although high-dose chemotherapy is rapidly gaining acceptance as a treatment option for a number of cancers , the long-term toxic effects of such therapy are a concern . Cognitive deficits ( e.g. , problems with memory and concentration ) are not uncommon after chemotherapy , but they have not been documented systematic ally . In this study , we assessed the prevalence of cognitive deficits in a group of patients with high-risk breast cancer who were r and omly assigned to receive either high-dose or st and ard-dose adjuvant chemotherapy plus tamoxifen , and we investigated whether high-dose chemotherapy impaired cognitive functioning more than st and ard-dose chemotherapy . METHODS Cognitive functioning was evaluated by use of a battery of neuropsychologic tests . In addition , patients were interviewed with regard to cognitive problems , health-related quality of life , anxiety , and depression . Results from patients who received adjuvant systemic therapy were compared with results from patients who had early stage breast cancer not treated with such therapy ( control patients ) . RESULTS The study population consisted of 34 patients treated with high-dose chemotherapy plus tamoxifen , 36 patients treated with st and ard-dose chemotherapy plus tamoxifen , and 34 control patients . For all patients , the average time since the completion of last nonhormonal therapy was 2 years . Cognitive impairment was found in 32 % of the patients treated with high-dose chemotherapy , in 17 % of the patients treated with st and ard-dose chemotherapy , and in 9 % of the control patients . In comparison with the control patients , patients treated with high-dose chemotherapy appeared to have an 8.2-times higher risk of cognitive impairment ( odds ratio ; 95 % confidence interval [ CI ] = 1.8 - 37.7 ) ; in comparison with the patients who received st and ard-dose chemotherapy , this risk of impairment was 3.5-times higher ( 95 % CI = 1.0 - 12.8 ) . CONCLUSION High-dose chemotherapy appears to impair cognitive functioning more than st and ard-dose chemotherapy . Central nervous system toxicity may be a dose-limiting factor in high-dose chemotherapy regimens ABSTRACT The primary aim of the current study was to examine whether neurocognitive functioning among breast cancer survivors ( BCS ) exposed to systemic adjuvant chemotherapy differs from that seen among BCS who did not receive chemotherapy . The performance of each of these BCS groups was compared to a demographically matched comparison group without history of breast cancer , a group not included in the majority of previous cognitive functioning studies . We also sought to explore whether usage of the anti-estrogen drug tamoxifen , a common component of breast cancer treatment , was related to neurocognitive functioning . Finally , we wished to examine the relationship between subjective report of cognitive functioning and objective performance on neurocognitive measures among BCS . Fifty-three survivors of breast cancer ( all between 2–5 years after diagnosis and initial surgical removal of cancerous tissue ) and 19 healthy non-BCS comparison subjects were administered a comprehensive neurocognitive battery , and measures of mood , energy level , and self-reported cognitive functioning . Those BCS who received adjuvant chemotherapy performed significantly worse in the domains of verbal learning , visuospatial functioning , and visual memory than BCS treated with surgery only . Those who received both chemotherapy and tamoxifen showed the greatest compromise . Although patients who received chemotherapy ( with and without tamoxifen ) performed worse than those treated with surgery only on several domains , neither group was significantly different from demographically matched comparison subjects without a history of breast cancer . Finally , we found no relationship between subjective cognitive complaints and objective performance , although cognitive complaints were associated with measures of psychological distress and fatigue . We highlight ways in which these data converge with other recent studies to suggest that systemic chemotherapy , especially in combination with tamoxifen , can have adverse yet subtle effects on cognitive functioning A number of patients who have undergone adjuvant ( CMF ) chemotherapy for operative primary breast carcinoma have reported impaired cognitive function , sometimes even years after completion of therapy . The possible role of cytostatic treatment as a causative factor has scarcely been investigated . The objective of the current study was to examine the late effects on neuropsychologic functioning of CMF adjuvant chemotherapy given to patients with breast carcinoma The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen . We performed a population -based study in the county of North Jutl and , Denmark , including 120 women aged < 60 years who received adjuvant chemotherapy with seven cycles of cyclophosphamide , epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006 . They were compared with an aged-matched group of 208 women without previous cancer selected r and omly from the same population . Data were collected before start of adjuvant treatment and after 6 months by neuropsychological tests and question naires to evaluate cognitive function , quality of life and psychological distress . Neuropsychological tests did not reveal any differences in cognitive function between breast cancer patients after chemotherapy and healthy controls . Patients rated their own cognitive functions as improved after 6 months , and patients , who did not receive adjuvant medical treatment , reached the same level as controls within 6 months . Patients receiving chemotherapy or tamoxifen were up to three times more likely than controls to rate themselves as impaired at 6 months . Our results do not support that adjuvant chemotherapy is associated with cognitive side effects in breast cancer patients Numerous studies have shown that there are acute cognitive side-effects of chemotherapy for breast cancer . Presumably , patients are more concerned about chronic treatment effects . This report from a prospect i ve longitudinal study compares cognitive functioning in 56 breast cancer patients 1 year after chemotherapy to that of 56 healthy individuals . Neuropsychological test scores were combined into verbal memory , visual memory , working memory , and processing speed scores , as well as an overall summary score , and analyzed using multi-level growth modeling . Frequency of cognitive decline was assessed using regression-based change scores . There was significant rebound in the overall summary score from end of treatment to 1-year follow-up as well as a substantial reduction in the frequency of cognitive decline . However , more than one-third of the breast cancer patients who showed cognitive decline immediately following completion of chemotherapy showed persistent cognitive decline 1 year later . Furthermore , recovery was not seen in all cognitive domains . In fact , the rebound was significant only for working memory . Longer multi-site studies are recommended to explore the risk factors for and the permanence of these longer-term cognitive effects Repeat administrations of the Wisconsin Card Sorting Test ( WCST ) are a common clinical practice to assess changes in cognitive functions of individuals recovering from traumatic brain injury ( TBI ) . Yet , little is even known about the performance of healthy individuals on repeat administrations of the test . The present study compared the effects of repeat administration of the WCST in normal individuals and survivors of traumatic brain injury . Normal participants were administered the WCST twice , with a 5-month interval between testings and the findings were compared to the data from patients with TBI tested twice . Normal controls only modestly improved their performance on repeat testing . In contrast , using a reliability of change ( RC ) index , TBI survivors demonstrated clinical ly meaningful gains in performance |
12,466 | 21,151,770 | Collectively , these studies suggest that specific mind-body practice s may help alleviate pain and enhance physical function in adults suffering from osteoarthritis of the knee . | Osteoarthritis of the knee is a major cause of disability among adults worldwide .
Important treatment options include nonpharmacologic therapies , and especially symptom management strategies in which patients take an active role .
Among these , mind-body therapies may have particular promise for alleviating the distressful symptoms associated with osteoarthritis of the knee .
However , systematic review s are lacking .
The objective of this paper is to review English- language articles describing clinical studies evaluating the effects of patient-driven mind-body therapies on symptoms of knee osteoarthritis . | BACKGROUND Stress can affect health . There is a growing need for the evaluation and application of professional stress management options , i.e , stress reduction . Mind/body medicine serves this goal , e.g , by integrating self-care techniques into medicine and health care . Tai Chi ( TC ) can be classified as such a mind/body technique , potentially reducing stress and affecting physical as well as mental health parameters , which , however , has to be examined further . MATERIAL / METHODS We conducted a prospect i ve , longitudinal pilot study over 18 weeks for the evaluation of subjective and objective clinical effects of a Yang style TC intervention in young adults ( beginners ) by measuring physiological ( blood pressure , heart rate , saliva cortisol ) and psychological ( SF-36 , perceived stress , significant events ) parameters , i.e , direct or indirect indicators of stress and stress reduction , in a non-r and omised/-controlled , yet non-selected cohort ( n=21 ) by pre-to-post comparison and in follow-up . SF-36 values were also compared with the age-adjusted norm population , serving as an external control . Additionally , we measured diurnal cortisol profiles in a cross-sectional sub- study ( n=2 + 2 , pre-to-post ) , providing an internal r and om control sub- sample . RESULTS Only nine participants completed all measurements . Even so , we found significant ( p<0.05 ) reductions of saliva cortisol ( post and follow-up ) , which seems to be an indicator of general stress reduction . A significant decrease in perceived mental stress ( post ) proved even highly significant ( p<0.01 ) in the follow-up , whereas physical stress perception declined to a much lesser degree . Significant improvements were also detected for the SF-36 dimensions general health perception , social functioning , vitality , and mental health/psychological well-being . Thus , the summarized mental health measures all clearly improved , pointing towards a predominantly psychological impact of TC . CONCLUSIONS Subjective health increased , stress decreased ( objective ly and subjectively ) during TC practice . Future studies should confirm this observation by rigorous methodology and by further combining physical and psychological measurements with basic research , thereby also gaining knowledge of autoregulation and molecular physiology that possibly underlies mind/body medicine Background : Dance and yoga have been shown to produce improvements in psychological well-being . Purpose : The aim of this study was to examine some of the psychological and neuroendocrine responses to these activities . Methods : Sixty-nine healthy college students participated in one of three 90-min classes : African dance ( n = 21 ) , Hatha yoga ( n = 18 ) , or a biology lecture as a control session ( n = 30 ) . Before and after each condition participants completed the Perceived Stress Scale ( PSS ) , completed the Positive Affect and Negative Affect Schedule , and provided a saliva sample for cortisol . Results : There were significant reductions in PSS and negative affect ( ps < .0001 ) and Time × Treatment interactions ( ps < .0001 ) such that African dance and Hatha yoga showed significant declines , whereas there was no significant change in biology lecture . There was no significant main effect for positive affect ( p = .53 ) , however there was a significant interaction effect ( p < .001 ) such that positive affect increased in African dance , decreased in biology lecture , and did not change significantly in Hatha yoga . There was a significant main effect for salivary cortisol ( p < .05 ) and a significant interaction effect ( p < .0001 ) such that cortisol increased in African dance , decreased in Hatha yoga , and did not change in biology . Changes in cortisol were not significantly related to changes in psychological variables across treatments . There was 1 significant interaction effect ( p = .04 ) such that change in positive affect and change in cortisol were negatively correlated in Hatha yoga but positively correlated in African dance and biology . Conclusions : Both African dance and Hatha yoga reduced perceived stress and negative affect . Cortisol increased in African dance and decreased in Hatha yoga . Therefore , even when these interventions produce similar positive psychological effects , the effects may be very different on physiological stress processes . One factor that may have particular salience is the amount of physiological arousal produced by the intervention PURPOSE Tai Chi exercise , an ancient Chinese martial art , has drawn more and more attention for its health benefits . The purpose of the study was to identify the effects of a Sun-style Tai Chi exercise on arthritic symptoms ( joint pain and stiffness ) , motivation for performing health behaviors , and the performance of health behaviors among older women with osteoarthritis . METHODS Total of 72 women with the mean age of 63 years old were recruited from out patients clinic or public health centers according to the inclusion criteria and assigned r and omly to either the Tai Chi exercise group or the control . A Sun-style Tai Chi exercise has been provided three times a week for the first two weeks , and then once a week for another 10 weeks . In 12 weeks of study period , 22 subjects in the Tai Chi exercise group and 21 subjects in the control group completed the posttest measure with the dropout rate of 41 % . Outcome variables included arthritic symptoms measured by K-WOMAC , motivation for health behavior , and health behaviors . RESULTS At the completion of the 12 week Tai Chi exercise , the Tai Chi group perceived significantly less joint pain ( t=-2.19 , p=0.03 ) and stiffness ( t=-2.24 , p=0.03 ) , perceived more health benefits ( t=2.67 , p=0.01 ) , and performed better health behaviors ( t=2.35 , p=0.02 ) , specifically for diet behavior ( t=2.06 , p=0.04 ) and stress management ( t=2.97 , p=0.005 ) . CONCLUSION A Sun-style Tai Chi exercise was found as beneficial for women with osteoarthritis to reduce their perceived arthritic symptoms , improve their perception of health benefits to perform better health behaviors The present study aim ed at assessing the effects of a set of yoga practice s on normal adults ( n = 37 ) , children ( n = 86 ) , and patients with rheumatoid arthritis ( n = 20 ) . An equal number of normal adults , children , and patients with rheumatoid arthritis who did not practice yoga were studied under each category , forming respective control groups . Yoga and control group subjects were assessed at baseline and after varying intervals , as follows , adults after 30 days , children after 10 days and patients after 15 days , based on the duration of the yoga program , which they attended , which was already fixed . H and grip strength of both h and s , measured with a grip dynamometer , increased in normal adults and children , and in rheumatoid arthritis patients , following yoga , but not in the corresponding control groups , showing no re-test effect . Adult female volunteers and patients showed a greater percentage improvement than corresponding adult males . This gender-based difference was not observed in children . Hence yoga practice improves h and grip strength in normal persons and in patients with rheumatoid arthritis , though the magnitude of improvement varies with factors such as gender and age Background : Mindfulness-based stress reduction ( MBSR ) proposes a systematic program for reduction of suffering associated with a wide range of medical conditions . Studies suggest improvements in general aspects of well-being , including quality of life ( QoL ) , coping and positive affect , as well as decreased anxiety and depression . Methods : A quasi-experimental study examined effects of an 8-week MBSR intervention among 58 female patients with fibromyalgia ( mean , 52 ± 8 years ) who underwent MBSR or an active social support procedure . Participants were assigned to groups by date of entry , and 6 subjects dropped out during the study . Self-report measures were vali date d German inventories and included the following scales : visual analog pain , pain perception , coping with pain , a symptom checklist and QoL. Pre- and postintervention measurements were made . Additionally , a 3-year follow-up was carried out on a subgroup of 26 participants . Results : Pre- to postintervention analyses indicated MBSR to provide significantly greater benefits than the control intervention on most dimensions , including visual analog pain , QoL subscales , coping with pain , anxiety , depression and somatic complaints ( Cohen d effect size , 0.40–1.10 ) . Three-year follow-up analyses of MBSR participants indicated sustained benefits for these same measures ( effect size , 0.50–0.65 ) . Conclusions : Based upon a quasi-r and omized trial and long-term observational follow-up , results indicate mindfulness intervention to be of potential long-term benefit for female fibromyalgia patients There is growing evidence that yoga may offer a safe and cost-effective intervention for Type 2 Diabetes mellitus ( DM 2 ) . However , systematic review s are lacking . This article critically review s the published literature regarding the effects of yoga-based programs on physiologic and anthropometric risk profiles and related clinical outcomes in adults with DM 2 . We performed a comprehensive literature search using four computerized English and Indian scientific data bases . The search was restricted to original studies ( 1970–2006 ) that evaluated the metabolic and clinical effects of yoga in adults with DM 2 . Studies targeting clinical population s with cardiovascular disorders that included adults with comorbid DM were also evaluated . Data were extracted regarding study design , setting , target population , intervention , comparison group or condition , outcome assessment , data analysis and presentation , follow-up , and key results , and the quality of each study was evaluated according to specific predetermined criteria . We identified 25 eligible studies , including 15 uncontrolled trials , 6 non-r and omized controlled trials and 4 r and omized controlled trials ( RCTs ) . Overall , these studies suggest beneficial changes in several risk indices , including glucose tolerance and insulin sensitivity , lipid profiles , anthropometric characteristics , blood pressure , oxidative stress , coagulation profiles , sympathetic activation and pulmonary function , as well as improvement in specific clinical outcomes . Yoga may improve risk profiles in adults with DM 2 , and may have promise for the prevention and management of cardiovascular complications in this population . However , the limitations characterizing most studies preclude drawing firm conclusions . Additional high- quality RCTs are needed to confirm and further eluci date the effects of st and ardized yoga programs in population s with DM 2 Objectives . This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer out patients undergoing adjuvant radiotherapy at a cancer center . Methods . Eighty-eight stage II and III breast cancer out patients are r and omly assigned to receive yoga ( n = 44 ) or brief supportive therapy ( n = 44 ) prior to radiotherapy treatment . Assessment s include diurnal salivary cortisol levels 3 days before and after radiotherapy and self-ratings of anxiety , depression , and stress collected before and after 6 weeks of radiotherapy . Results . Analysis of covariance reveals significant decreases in anxiety ( P < .001 ) , depression ( P = .002 ) , perceived stress ( P < .001 ) , 6 a.m. salivary cortisol ( P = .009 ) , and pooled mean cortisol ( P = .03 ) in the yoga group compared with controls . There is a significant positive correlation between morning salivary cortisol level and anxiety and depression . Conclusion . Yoga might have a role in managing self-reported psychological distress and modulating circadian patterns of stress hormones in early breast cancer patients undergoing adjuvant radiotherapy Context Yoga combines exercise with achieving a state of mental focus through breathing . In the United States , 1 million people practice yoga for low back pain . Contribution The authors recruited patients who had a recent primary care visit for low back pain and r and omly assigned 101 to yoga or conventional exercise or a self-care book . Patients in the yoga and exercise groups reported good adherence at 26 weeks . Compared with self-care , symptoms were milder and function was better with yoga . The exercise group had intermediate outcomes . Symptoms improved between 12 and 26 weeks only with yoga . Implication s Yoga was a more effective treatment for low back pain than a self-care book . The Editors Most treatments for chronic low back pain have modest efficacy at best ( 1 ) . Exercise is one of the few proven treatments for chronic low back pain ; however , its effects are often small , and no form has been shown to be clearly better than another ( 2 - 5 ) . Yoga , which often couples physical exercise with breathing , is a popular alternative form of mindbody therapy . An estimated 14 million Americans practice d yoga in 2002 ( 6 ) , including more than 1 million who used it as a treatment for back pain ( 7 , 8) . Yoga may benefit patients with back pain simply because it involves exercise or because of its effects on mental focus . We found no published studies in western biomedical literature that evaluated yoga for chronic low back pain ; therefore , we design ed a clinical trial to evaluate its effectiveness and safety for this condition . Methods Study Design and Setting This r and omized , controlled trial compared the effects of yoga classes with conventional exercise classes and with a self-care book in patients with low back pain that persisted for at least 12 weeks . The study was conducted at Group Health Cooperative , a nonprofit , integrated health care system with approximately 500000 enrollees in Washington State and Idaho . The Group Health Cooperative institutional review board approved the study protocol , and all study participants gave oral informed consent before the eligibility screening and written consent before the baseline interview and r and omization . Patients Patients from Group Health Cooperative were recruited for 12-week sessions of classes that were conducted between June and December 2003 . We mailed letters describing the study to 6913 patients between 20 and 64 years of age who had visited a primary care provider for treatment of back pain 3 to 15 months before the study ( according to electronic visit records ) . We also advertised the study in the health plan 's consumer magazine . Patients were informed that we were comparing 3 approaches for the relief of back pain and that each was design ed to help reduce the negative effects of low back pain on people 's lives . A research assistant telephoned patients who returned statements of interest to assess their eligibility . After we received their signed informed consent forms , eligible patients were telephoned again for collection of baseline data and r and omization to treatment . We excluded individuals whose back pain was complicated ( for example , sciatica , previous back surgery , or diagnosed spinal stenosis ) , potentially attributable to specific underlying diseases or conditions ( for example , pregnancy , metastatic cancer , spondylolisthesis , fractured bones , or dislocated joints ) , or minimal ( rating of less than 3 on a bothersomeness scale of 0 to 10 ) . We also excluded individuals who were currently receiving other back pain treatments or had participated in yoga or exercise training for back pain in the past year , those with a possible disincentive to improve ( such as patients receiving workers ' compensation or those involved in litigation ) , and those with unstable medical or severe psychiatric conditions or dementia . Patients who had contraindications ( for example , symptoms consistent with severe disk disease ) or schedules that precluded class participation , those who were unwilling to practice at home , or those who could not speak or underst and English were also excluded . R and omization Protocol Participants were r and omly assigned to participate in yoga or exercise classes or to receive the self-care book . We r and omly generated treatment assignments for each class series by using a computer program with block sizes of 6 or 9 . A research er who was not involved in patient recruitment or r and omization placed the assignments in opaque , sequentially numbered envelopes , which were stored in a locked filing cabinet until needed for r and omization . Interventions The yoga and exercise classes developed specifically for this study consisted of 12 weekly 75-minute classes design ed to benefit people with chronic low back pain . In addition to attending classes held at Group Health facilities , participants were asked to practice daily at home . Participants received h and outs that described home practice s , and yoga participants received auditory compact discs to guide them through the sequence of postures with the appropriate mental focus ( examples of postures are shown in the Appendix Figure ) . Study participants retained access to all medical care provided by their insurance plan . Appendix Figure . Yoga postures Yoga We chose to use viniyoga , a therapeutically oriented style of yoga that emphasizes safety and is relatively easy to learn . Our class instructor and a senior teacher of viniyoga , who has + written a book about its therapeutic uses ( 9 ) , design ed the yoga intervention for patients with back pain who did not have previous yoga experience . Although all the sessions emphasized use of postures and breathing for managing low back symptoms , each had a specific focus : relaxation ; strength-building , flexibility , and large-muscle movement ; asymmetric poses ; strengthening the hip muscles ; lateral bending ; integration ; and customizing a personal practice . The postures were selected from a core of 17 relatively simple postures , some with adaptations ( Appendix Table ) , and the sequence of the postures in each class was performed according to the rudiments of viniyoga ( 9 ) . Each class included a question - and -answer period , an initial and final breathing exercise , 5 to 12 postures , and a guided deep relaxation . Most postures were not held but were repeated 3 or 6 times . Exercise Because we could not identify a clearly superior form of therapeutic exercise for low back pain from the literature , a physical therapist design ed a 12-session class series that was 1 ) different from what most participants would have probably experienced in previous physical therapy sessions ( to maximize adherence ) and 2 ) similar to the yoga classes in number and length . We included a short educational talk that provided information on proper body mechanics , the benefits of exercise and realistic goal setting , and overcoming common barriers to developing an exercise routine ( for example , fear ) . Each session began with the educational talk ; feedback from the previous week ; simple warm-ups to increase heart rate ; and repetitions of a series of 7 aerobic exercises and 10 strengthening exercises that emphasized leg , hip , abdominal , and back muscles . Over the course of the 12-week series , the number of repetitions of each aerobic and strength exercise increased from 8 to 30 in increments of 2 . The strengthening exercises were followed by 12 stretches for the same muscle groups ; each stretch was held for 30 seconds . Classes ended with a short , unguided period of deep , slow breathing . Self-Care Book Participants were mailed a copy of The Back Pain Helpbook ( 10 ) , an evidence -based book that emphasized such self-care strategies as adoption of a comprehensive fitness and strength program , appropriate lifestyle modification , and guidelines for managing flare-ups . Although we did not provide any instructions for using the book , many of the chapters concluded with specific action items . Outcome Measures Interviewers who were masked to the treatment assignments conducted telephone interviews at baseline and at 6 , 12 , and 26 weeks after r and omization . The baseline interview collected information regarding sociodemographic characteristics , back pain history , and the participant 's level of knowledge about yoga and exercise . Participants were asked to describe their current pain and to rate their expectations for each intervention . The primary outcomes were back-related dysfunction and symptoms , and the primary time point of interest was 12 weeks . We used the modified Rol and Disability Scale ( 11 ) to measure patient dysfunction by totaling the number of positive responses to 23 questions about limitations of daily activities that might arise from back pain . This scale has been found to be valid , reliable , and sensitive to change ( 12 - 14 ) ; research ers estimate that the minimum clinical ly significant difference on the Rol and scale ranges from 2 to 3 points ( 13 , 15 ) . Participants rated how bothersome their back pain had been during the previous week on an 11-point scale , in which 0 represented not at all bothersome and 10 represented extremely bothersome ; a similar measure demonstrated substantial construct validity in earlier research ( 13 ) . Estimates of the minimum clinical ly significant difference on the bothersomeness scale were approximately 1.5 points ( 16 , 17 ) . Secondary outcome measures were general health status , which we assessed by conducting the Short Form-36 Health Survey ( 18 ) ; degree of restricted activity as determined by patient responses to 3 questions ( 19 ) ; and medication use . After all outcomes data were collected , we asked questions related to specific interventions ( for example , Did you practice at home ? ) . At the 12-week interview , we asked class participants about any pain or substantial discomfort they experienced as a result of the classes . We assessed adherence to the home practice recommendations by asking class participants to complete weekly home practice logs and by asking about home practice during the follow-up Our previous study has demonstrated that 6 weeks of Tai Chi exercise significantly improves knee pain and stiffness in elderly with knee osteoarthritis . This study also examine the effects of Tai Chi exercise on gait kinematics , physical function , pain , and pain self-efficacy in elderly with knee osteoarthritis . In this prospect i ve , pretest-posttest clinical trial , 40 men and women ( 64.4+/-8.3 years ) diagnosed with knee osteoarthritis participated in 6 weeks of instructed Tai Chi training , 1 hour/session , 2 sessions/week . The following measures were taken at baseline and the conclusion of the intervention : ( a ) gait kinematics including stride length , stride frequency , and gait speed quantified using video analysis , ( b ) physical function , ( c ) knee pain , and ( d ) pain self-efficacy . Data were analyzed using repeated MANCOVA , MANOVA , ANOVA and Wilcoxon tests . After 6 weeks of Tai Chi exercise , stride length ( p=0.023 ; 1.17+/-0.17 vs. 1.20+/-0.14 m ) , stride frequency ( p=0.014 ; 0.91+/-0.08 vs. 0.93+/-0.08 strides/s ) , and consequently gait speed ( p<0.025 ; 1.06+/-0.19 vs. 1.12+/-0.15 m/s ) increased in the participants . Physical function was significantly improved ( p<0.001 ) and knee pain was significantly decreased ( p=0.002 ) , while no change was observed in pain self-efficacy . In conclusion , these findings support that Tai Chi is beneficial for gait kinematics in elderly with knee osteoarthritis , and a longer term application is needed to substantiate the effect of Tai Chi as an alternative exercise in management of knee osteoarthritis OBJECTIVES The American College of Rheumatology ( ACR ) Guidelines for the medical management of osteoarthritis ( OA ) emphasize the use of nonpharmacologic interventions including exercise . Implementation of an exercise program can be difficult for patients , and little is known about the benefits of alternative therapies such as yoga . The aim of this pilot study was to assess the feasibility of using yoga in the tradition of B.K.S. Iyengar to treat the symptoms of osteoarthritis of the knee . DESIGN Participants were instructed in modified Iyengar yoga postures during 90-minute classes once weekly for 8 weeks . SUBJECTS Participants met ACR criteria for osteoarthritis of the knee and completed a medical history and physical examination , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , Arthritis Impact Measurement Scale 2 ( AIMS 2 ) , Patient Global Assessment ( GA ) by Visual Analog Scale ( VAS ) , Physician GA by VAS , and 50-foot Walk Time before and following an 8-week course of yoga instruction . Eleven ( 11 ) subjects enrolled , nine completed at least one session and seven ( six of whom were obese ) had data from pre- and post-course time points available for analysis . RESULTS Statistically significant reductions in WOMAC Pain , WOMAC Physical Function , and AIMS 2 Affect were observed when participants ' status were compared to their pre-course status . WOMAC Stiffness , AIMS 2 Symptoms , Social and Role , Physician GA , and Patient GA measured trends in improvement of symptoms . No adverse events from treatment were reported . CONCLUSIONS This pilot study suggests that yoga may provide a feasible treatment option for previously yoga-naive , obese patients > 50 years of age and offers potential reductions in pain and disability caused by knee OA . Future studies should compare yoga to other nonpharmacologic interventions for knee OA , such as patient education or quadriceps-strengthening exercises OBJECTIVE The aim of this study was to investigate the effectiveness of a qigong training program in reducing stress in hospital staff . METHODS Subjects were r and omly assigned to a 6-week intervention of either qigong practice ( n = 16 ) or a waiting list ( n = 21 ) . The primary measure of stress was the Perceived Stress Scale . Secondary measures included the Short Form 36 ( SF-36 ) quality -of-life measure and a 100-mm analog pain scale . RESULTS The qigong group demonstrated a statistically significant reduction of perceived stress compared to the control group ( p = 0.02 ) . On the Social Interaction subscale of the SF-36 , the qigong group demonstrated greater improvement compared to controls ( p = 0.04 ) . Within-groups analyses demonstrated that the qigong group ( p = 0.03 ) , but not the control group , experienced a significant reduction of pain intensity . A regression analysis demonstrated an association between higher baseline stress levels and greater improvement within the qigong group ( R(2 ) = 0.34 ; p = 0.02 ) . CONCLUSIONS These results suggest that short-term exposure to qigong was effective in reducing stress in hospital staff . Further studies are needed to evaluate the possible effectiveness of qigong in reducing pain and in improving quality of life Low back pain is a significant public health problem and one of the most commonly reported reasons for the use of Complementary Alternative Medicine . A r and omized control trial was conducted in subjects with non‐specific chronic low back pain comparing Iyengar yoga therapy to an educational control group . Both programs were 16 weeks long . Subjects were primarily self‐referred and screened by primary care physicians for study of inclusion /exclusion criteria . The primary outcome for the study was functional disability . Secondary outcomes including present pain intensity , pain medication usage , pain‐related attitudes and behaviors , and spinal range of motion were measured before and after the interventions . Subjects had low back pain for 11.2±1.54 years and 48 % used pain medication . Overall , subjects presented with less pain and lower functional disability than subjects in other published intervention studies for chronic low back pain . Of the 60 subjects enrolled , 42 ( 70 % ) completed the study . Multivariate analyses of outcomes in the categories of medical , functional , psychological and behavioral factors indicated that significant differences between groups existed in functional and medical outcomes but not for the psychological or behavioral outcomes . Univariate analyses of medical and functional outcomes revealed significant reductions in pain intensity ( 64 % ) , functional disability ( 77 % ) and pain medication usage ( 88 % ) in the yoga group at the post and 3‐month follow‐up assessment s. These preliminary data indicate that the majority of self‐referred persons with mild chronic low back pain will comply to and report improvement on medical and functional pain‐related outcomes from Iyengar yoga therapy OBJECTIVES To assess the feasibility and safety of using the health-promoting traditional Chinese exercise , known as Baduanjin , in treating knee osteoarthritis ( OA ) . SUBJECTS Twenty-eight ( 28 ) female patients who met the American College of Rheumatology criteria for osteoarthritis of the knee signed the informed consent and were r and omized into the Baduanjin group ( n=14 ) and the control group ( n=14 ) . Eleven ( 11 ) patients in the Baduanjin group and 10 patients in the control group completed the trial . INTERVENTION The Baduanjin group patients exercised following taped comm and s in the community entertainment room during 30-minute classes five times a week for 8 weeks , whereas the control group received no treatment . OUTCOME MEASURES Indicators that include knee pain , stiffness , physical disability , general health , quadriceps strength , and aerobic ability were measured using the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , the Medical Outcomes Study Short Form-36 ( SF-36 ) , the 6-Minute Walk Test ( 6-MWT ) , and the Isokinetic Strength of the Knee Extensors ( ISKE ) . RESULTS Compared with the control group , the participants in the Baduanjin group had statistically significant improvements in percentage changes of the WOMAC pain subscale ( -61.8+/-35.7 % versus 44.6+/-102.8 % ; p=0.006 ) , the WOMAC stiffness subscale ( -53.4+/-46.1 % versus 135.8+/-386.7 % ; p=0.029 ) , the WOMAC physical function subscale ( -7.4+/-81.9 % versus 140.5+/-151.9 % ; p=0.024 ) , 6-MWT ( 11.9+/-7.5 % versus 1.6+/-13.0 % ; p=0.036 ) , and Peak Torque of the ISKE ( 15.1+/-33.7 % versus -16.1+/-16.6 % ; p=0.016 ) . The SF-36 's General Health , Social Function , and Mental Health subscales had no significant changes between those in the Baduanjin and control groups . As such , no adverse events from treatment were reported . CONCLUSIONS This study suggested that the Baduanjin exercise provided a safe and feasible treatment option for patients with knee OA , as well as offered reductions in pain , stiffness , and disability , which helped improve the patients ' quadriceps strength and aerobic ability OBJECTIVES This study aim ed to verify whether techniques of yoga with and without the addition of Tui Na might improve pain and the negative impact of fibromyalgia ( FMS ) on patients ' daily life . DESIGN Forty ( 40 ) FMS women were r and omized into two groups , Relaxing Yoga ( RY ) and Relaxing Yoga plus Touch ( RYT ) , for eight weekly sessions of stretching , breathing , and relaxing yogic techniques . RYT patients were further su bmi tted to manipulative techniques of Tui Na . OUTCOME MEASURE Outcome measures comprised the Fibromyalgia Impact Question naire ( FIQ ) , pain threshold at the 18 FMS tender points , and a verbal graduation of pain assessed before treatment and on the followup . The visual analog scale ( VAS ) for pain was assessed before and after each session and on the follow-up . RESULTS Seventeen ( 17 ) RYT and 16 RY patients completed the study . Both RY and RYT groups showed improvement in the FIQ and VAS scores , which decreased on all sessions . The RYT group showed lower VAS and verbal scores for pain on the eighth session , but this difference was not maintained on the follow-up . Conversely , RY VAS and verbal scores were significantly lower just on the follow-up . CONCLUSIONS These study results showed that yogic techniques are valid therapeutic methods for FMS . Touch addition yielded greater improvement during the treatment . Over time , however , RY patients reported less pain than RYT . These results suggest that a passive therapy may possibly decrease control over FMS symptoms OBJECTIVE The aim of this study was to compare the effect of a short-term intensive residential yoga program with physical exercise ( control ) on pain and spinal flexibility in subjects with chronic low-back pain ( CLBP ) . DESIGN This was a wait-list , r and omized controlled study . SETTING The study was conducted at a residential integrative health center in Bangalore , South India . SUBJECTS Eighty ( 80 ) subjects ( females , n = 37 ) with CLBP , who consented were r and omly assigned to receive yoga or physical exercise if they satisfied the selection criteria . INTERVENTION The intervention consisted of a 1-week intensive residential yoga program comprised of asanas ( physical postures ) design ed for back pain , pranayamas ( breathing practice s ) , meditation , and didactic and interactive sessions on philosophical concepts of yoga . The control group practice d physical exercises under a trained physiatrist and also had didactic and interactive sessions on lifestyle change . Both of the groups were matched for time on intervention and attention . OUTCOME MEASURES Pain-related outcomes were assessed by the Oswestry Disability Index ( ODI ) and by spinal flexibility , which was assessed using goniometer at pre and post intervention . Data were analyzed using repeated measures analysis of variance ( RMANOVA ) . RESULTS Data conformed to a Gaussian distribution . There was a significant reduction in ODI scores in the yoga group compared to the control group ( p = 0.01 ; effect size 1.264 ) . Spinal flexibility measures improved significantly in both groups but the yoga group had greater improvement as compared to controls on spinal flexion ( p = 0.008 ; effect size 0.146 ) , spinal extension ( p = 0.002 ; effect size 0.251 ) , right lateral flexion ( p = 0.059 ; effect size 0.006 ) ; and left lateral flexion ( p = 0.006 ; effect size 0.171 ) . CONCLUSIONS Seven ( 7 ) days of a residential intensive yoga-based lifestyle program reduced pain-related disability and improved spinal flexibility in patients with CLBP better than a physical exercise regimen Objective : To evaluate the effects of tai chi consisting of group and home-based sessions in elderly subjects with knee osteoarthritis . Design : A r and omized , controlled , single-blinded 12-week trial with stratification by age and sex , and six weeks of follow-up . Setting : General community . Participants : Forty-one adults ( 709 / 9.2 years ) with knee osteoarthritis . Interventions : The tai chi programme featured six weeks of group tai chi sessions , 40 min/session , three times a week , followed by another six weeks ( weeks 7 -12 ) of home-based tai chi training . Subjects were requested to discontinue tai chi training during a six-week follow-up detraining period ( weeks 13 - 18 ) . Subjects in the attention control group attended six weeks of health lectures following the same schedule as the group-based tai chi intervention ( weeks 0 -6 ) , followed by 12 weeks of no activity ( weeks 7 - 18 ) . Main outcome measures : Knee pain measured by visual analogue scale , knee range of motion and physical function measured by Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) were recorded at baseline and every three weeks throughout the 18-week study period . Data were analysed using a mixed model ANOVA . Results : The six weeks of group tai chi followed by another six weeks of home tai chi training showed significant improvements in mean overall knee pain ( P = 0.0078 ) , maximum knee pain ( P = 0.0035 ) and the WOMAC subscales of physical function ( P = 0.0075 ) and stiffness ( P = 0.0206 ) compared to the baseline . No significant change of any outcome measure was noted in the attention control group throughout the study . The tai chi group reported lower overall pain and better WOMAC physical function than the attention control group at weeks 9 and 12 . All improvements disappeared after detraining Objective : To evaluate the effects of Tai Chi Qigong training on the quality of life and physical function of patients with osteoarthritis of the knee . Design : A preliminary , single-blind , r and omized controlled trial . Setting : General community , performed at Hwaseong City Health Center . Participants : Forty-four elderly subjects ( mean age , 69.1 ± 5.4 years ) with knee osteoarthritis . Intervention : The patients were r and omized ( 2:1 ) to : ( 1 ) an eight-week Tai Chi Qigong training programme or ( 2 ) a waiting list control group . The programme involved eight weeks of group Tai Chi Qigong sessions , with 60 minutes per session twice a week . Main outcome measures : The primary outcome was quality of life measured with the Short Form 36 ( SF-36 ) at baseline and week 8 . Secondary outcomes included the Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) and 6-m walking time . Results : The training group had statistically significant improvements in the quality of life ( changes of SF-36 , Qigong versus control : 21.6 ± 16.8 versus 9.8 ± 13.6 , P<0.05 ) and 6-m walking test ( change in walking time , Qigong versus control : —1.6 ± 1.7 versus —0.2 ± 0.8 s , P<0.01 ) . The WOMAC scores in the training group were markedly improved , although the differences were not statistically significant . Conclusions : Tai Chi Qigong training appears to have beneficial effects in terms of the quality of life and physical functioning of elderly subjects with knee osteoarthritis . However , more rigorous trials are needed to confirm the efficacy of this training for patients with osteoarthritis of the knee OBJECTIVE To determine the effects of T'ai Chi training on arthritis self-efficacy , quality of life indicators , and lower extremity functional mobility in older adults with osteoarthritis . DESIGN A prospect i ve , r and omized , controlled clinical trial . Intervention length was 12 weeks , with outcomes measured before and after intervention using blinded testers . Group ( T'ai Chi vs Control ) x time ( 2 x 2 ) mixed factorial ANOVA . SETTING Allied Health Sciences Center at Springfield College , Springfield , MA PARTICIPANTS : A total of 33 community-dwelling participants ( mean age 68 ) diagnosed with lower extremity osteoarthritis and having no prior T'ai Chi training longer than 2 weeks . INTERVENTION T'ai Chi training included two 1-hour T'ai Chi classes per week for 12 weeks . MEASUREMENTS Arthritis self-efficacy ( Arthritis Self-Efficacy Scale ) , quality of life indicators ( Arthritis Impact Measurement Scale ) , functional outcomes ( one-leg st and ing balance , 50-foot walking speed , time to rise from a chair ) . RESULTS T'ai Chi participants experienced significant ( P < .05 ) improvements in self-efficacy for arthritis symptoms , total arthritis self-efficacy , level of tension , and satisfaction with general health status . CONCLUSIONS A moderate T'ai Chi intervention can enhance arthritis self-efficacy , quality of life , and functional mobility among older adults with osteoarthritis . T'ai Chi training is a safe and effective complementary therapy in the medical management of lower extremity osteoarthritis PURPOSE The purpose of this r and omized pilot study was to evaluate a possible design for a 6-week modified hatha yoga protocol to study the effects on participants with chronic low back pain . PARTICIPANTS Twenty-two participants ( M = 4 ; F = 17 ) , between the ages of 30 and 65 , with chronic low back pain ( CLBP ) were r and omized to either an immediate yoga based intervention , or to a control group with no treatment during the observation period but received later yoga training . METHODS A specific CLBP yoga protocol design ed and modified for this population by a certified yoga instructor was administered for one hour , twice a week for 6 weeks . Primary functional outcome measures included the forward reach ( FR ) and sit and reach ( SR ) tests . All participants completed Oswestry Disability Index ( ODI ) and Beck Depression Inventory ( BDI ) question naires . Guiding questions were used for qualitative data analysis to ascertain how yoga participants perceived the instructor , group dynamics , and the impact of yoga on their life . ANALYSIS To account for drop outs , the data were divided into better or not categories , and analyzed using chi-square to examine differences between the groups . Qualitative data were analyzed through frequency of positive responses . RESULTS Potentially important trends in the functional measurement scores showed improved balance and flexibility and decreased disability and depression for the yoga group but this pilot was not powered to reach statistical significance . Significant limitations included a high dropout rate in the control group and large baseline differences in the secondary measures . In addition , analysis of the qualitative data revealed the following frequency of responses ( 1 ) group intervention motivated the participants and ( 2 ) yoga fostered relaxation and new awareness/learning . CONCLUSION A modified yoga-based intervention may benefit individuals with CLB , but a larger study is necessary to provide definitive evidence . Also , the impact on depression and disability could be considered as important outcomes for further study . Additional functional outcome measures should be explored . This pilot study supports the need for more research investigating the effect of yoga for this population CONTEXT Despite the growing popularity of qigong in the West , few well-controlled studies using a sham master to assess the clinical efficacy of qigong have been conducted . OBJECTIVE To study the effect of qigong on treatment-resistant patients with late-stage complex regional pain syndrome type I. DESIGN Block-r and om placebo-controlled clinical trial . SETTING Pain Management Center at New Jersey Medical School . PATIENTS 26 adult patients ( aged 18 to 65 years ) with complex regional pain syndrome type I. INTERVENTIONS The experimental group received qi emission and qigong instruction ( including home exercise ) by a qigong master . The control group received a similar set of instructions by a sham master . The experimental protocol included 6 forty-minute qigong sessions over 3 weeks , with reevaluation at 6 and 10 weeks . Assessment included comprehensive medical history , physical exam , psychological evaluation , necessary diagnostic testing . Symptom Check List 90 , and the Carleton University Responsiveness to Suggestion Scale . MAIN OUTCOME MEASURES Thermography , swelling , discoloration , muscle wasting , range of motion , pain intensity rating , medication usage , behavior assessment ( activity level and domestic disability ) , frequency of pain awakening , mood assessment , and anxiety assessment . RESULTS 22 subjects completed the protocol . Among the genuine qigong group , 82 % reported less pain by the end of the first training session compared to 45 % of control patients . By the last training session , 91 % of qigong patients reported analgesia compared to 36 % of control patients . Anxiety was reduced in both groups over time , but the reduction was significantly greater in the experimental group than in the control group . CONCLUSIONS Using a credible placebo to control for nonspecific treatment effects , qigong training was found to result in transient pain reduction and long-term anxiety reduction . The positive findings were not related to preexperimental differences between groups in hypnotizability . Future studies of qigong should control for possible confounding influences and perhaps use clinical disorders more responsive to psychological intervention Evidence indicates that low energy expenditure protocol s derived from traditional Chinese medicine may benefit patients with cardiac impairment ; therefore , the authors carried out a r and omized controlled trial to test a 16-week medically assisted qi gong training program for the physical rehabilitation of patients with stable chronic atrial fibrillation and preserved left ventricular function . Functional capacity variation was evaluated using the 6-minute walk test , which was performed at baseline , at the end of the intervention , and after 16 weeks . Thirty men and 13 women ( mean age , 68+/-8 years ) were r and omized to the intervention protocol or to a wait-list control group . Qi gong training was well tolerated and , compared with baseline , trained patients walked an average 114 meters more ( 27 % ) at the end of treatment ( P<.001 ) and 57 meters more ( 13.7 % ) 16 weeks later ( P=.008 ) . Control subjects showed no variation in functional capacity . These results seem promising and deserve confirmation with further research Osteoarthritis ( OA ) is a common , chronic condition that affects most older adults . Adults with OA must deal with pain that leads to limited mobility and may lead to disability and difficulty maintaining independence . A longitudinal , r and omized clinical trial pilot study was conducted to determine whether Guided Imagery ( GI ) with Progressive Muscle Relaxation ( PMR ) would reduce pain and mobility difficulties of women with OA . Twenty-eight older women with OA were r and omly assigned to either the treatment or the control group . The treatment consisted of listening twice a day to a 10-to-15-minute audiotaped script that guided the women in GI with PMR . Repeated- measures ANOVA revealed a significant difference between the two groups in the amount of change in pain and mobility difficulties they experienced over 12 weeks . The treatment group reported a significant reduction in pain and mobility difficulties at week 12 compared to the control group . Members of the control group reported no differences in pain and non-significant increases in mobility difficulties . The results of this pilot study justify further investigation of the effectiveness of GI with PMR as a self-management intervention to reduce pain and mobility difficulties associated with OA The objective of our study was to assess the efficacy of external qigong therapy ( EQT ) , a traditional Chinese medicine practice , in reducing pain and improving functionality of patients with knee osteoarthritis ( OA ) . One hundred twelve adults with knee OA were r and omized to EQT or sham treatment ( control ) ; 106 completed treatment and were analyzed . Two therapists performed EQT individually , five to six sessions in 3 weeks . The sham healer mimicked EQT for the same number of sessions and duration . Patients and examining physician were blinded . Primary outcomes were Western Ontario MacMaster ( WOMAC ) pain and function ; other outcomes included McGill Pain Question naire , time to walk 15 m , and range of motion squatting . Results of patients treated by the two healers were analyzed separately . Both treatment groups reported significant reduction in WOMAC scores after intervention . Patients treated by healer 2 reported greater reduction in pain ( mean improvement −25.7 ± 6.6 vs. −13.1 ± 3.0 ; p < 0.01 ) and more improvement in functionality ( −28.1 ± 9.7 vs. −13.2 ± 3.4 ; p < 0.01 ) than those in sham control and reduction in negative mood but not in anxiety or depression . Patients treated by healer 1 experienced improvement similar to control . The results of therapy persisted at 3 months follow-up for all groups . Mixed-effect models confirmed these findings with controlling for possible confounders . EQT might have a role in the treatment of OA , but our data indicate that all EQT healers are not equivalent . The apparent efficacy of EQT appears to be dependent on some quality of the healer . Further study on a larger scale with multiple EQT healers is necessary to determine the role ( if any ) of EQT in the treatment of OA and to identify differences in EQT techniques The r and omized clinical trial is the method of choice for comparing the effects of alternative care options , both in its own right and as the cornerstone of systematic review s of the subject . Errors in such trials , therefore , have major consequences for health care . This paper provides a brief introduction to the major sources of such errors , whether they be systematic or chance errors . It addresses selection bias , due to either biased entry in or biased exclusion from the trial , bias in assessing outcomes , and biases due to contamination or co-intervention . R and om errors , including type I and type II errors , are discussed along with ways in which they can be minimized . Small clinical trials , in particular , provide a major problem not only by themselves , but also if they become incorporated in systematic review s without appropriate consideration of the phenomenon of publication bias Study Design . A r and omized , controlled , multicenter trial : 1-year follow-up . Objective . To compare the effectiveness of qigong and exercise therapy in subjects with long-term nonspecific neck pain . Summary of Background Data . The evidence for the benefit of treatment programs focusing on persons with long-term , nonspecific neck pain is conflicting . Several studies have shown support for exercise therapy , but the efficacy of qigong has not been scientifically evaluated . Methods . A total of 122 patients were r and omly assigned to receive either qigong ( n = 60 ) or exercise therapy ( n = 62 ) . Most of them were women ( 70 % ) , and the mean age was 44 years . A maximum of 12 treatments were given over a period of 3 months . Neck pain frequency and intensity , neck disability ( NDI ) , grip strength , and cervical range of motion were recorded before and immediately after , at 6 months , and at 12 months after the treatment period . Changes in outcome variables were analyzed and dichotomized as improved or unchanged/deteriorated . Results . Clinical and demographic characteristics were similar among groups at baseline . No differences were found between the 2 interventions : qigong and exercise therapy . Both groups significantly improved immediately after treatment and this was maintained at the 6- and 12-month follow-ups in 5 of 8 outcome variables : average neck pain in the most recent week , current neck pain ( with exception for immediately after treatment period ) , neck pain diary , NDI , and cervical range of motion in rotation . Conclusion . These results indicate that treatments including supervised qigong or exercise therapy result ing in reduced pain and disability can be recommended for persons with long-term nonspecific neck pain This study aim ed to assess the efficacy of a 12-week Baduanjin qigong training program in preventing bone loss for middle-aged women . An experimental design was adopted , and subjects were assigned r and omly into an experimental group ( n = 44 ) and a control group ( n = 43 ) . The experimental group received a 12-week Baduanjin qigong training program , whereas the control group did not . Interleukin-6 ( IL-6 ) and bone mineral density ( BMD ) were measured before and after the intervention . The results showed significant differences in IL-6 ( t = -5.19 , p < 0.000 ) and BMD ( t = 1.99 , p = 0.049 ) between the groups . Baduanjin reduced IL-6 and maintained BMD in the experimental group . In conclusion , this study demonstrates promising efficacy of Baduanjin in preventing bone loss commonly occurring in middle-aged women . Thus , Baduanjin is valuable for promoting and maintaining the health status of middle-aged women OBJECTIVE To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis ( OA ) result in measurable clinical benefits . METHODS A r and omized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA . Participants were r and omly allocated for 12 weeks to hydrotherapy classes ( n = 55 ) , Tai Chi classes ( n = 56 ) , or a waiting list control group ( n = 41 ) . Outcomes were assessed 12 and 24 weeks after r and omization and included pain and physical function ( Western Ontario and McMaster Universities Osteoarthritis Index ) , general health status ( Medical Outcomes Study Short Form 12 Health Survey [ SF-12 ] , version 2 ) , psychological well-being , and physical performance ( Up and Go test , 50-foot walk time , timed stair climb ) . RESULTS At 12 weeks , compared with controls , participants allocated to hydrotherapy classes demonstrated mean improvements ( 95 % confidence interval ) of 6.5 ( 0.4 , 12.7 ) and 10.5 ( 3.6 , 14.5 ) for pain and physical function scores ( range 0 - 100 ) , respectively , whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 ( -0.8 , 11.1 ) and 9.7 ( 2.8 , 16.7 ) , respectively . Both class allocations achieved significant improvements in the SF-12 physical component summary score , but only allocation to hydrotherapy achieved significant improvements in the physical performance measures . All significant improvements were sustained at 24 weeks . In this almost exclusively white sample , class attendance was higher for hydrotherapy , with 81 % attending at least half of the available 24 classes , compared with 61 % for Tai Chi . CONCLUSION Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older , sedentary individuals with chronic hip or knee OA Regular exercise has been shown to benefit its practitioners and prevent and control diseases . Muscle/Tendon Change Classic ( MTCC ) qigong , characterized by simple , slow , and full-body exercise , is appropriate for the middle-age population . This study aims to evaluate the effect of the MTCC qigong program in improving physical status for middle-aged women . A quasi-experimental design was used . The experimental group ( n = 37 ) received an 8-week MTCC qigong program , whereas the control group ( n = 34 ) received none . Physiological parameters of muscular performance , body composition , and bone strength were measured before and after the program . The average age was 49 ± 4.13 years for the experimental group and 50 ± 4.74 years for the control group . The demographic characteristics were homogeneous between the two groups . There were statistically significant differences between the two groups in muscular endurance , body fat , waist-to-hip ratio , and body mass index at the completion of 8-week MTCC qigong program . The MTCC qigong could improve muscle endurance and body composition but not bone strength for middle-aged women , thereby demonstrating the qigong practice has certain health-preserving effects on women in this stage of life This study was design ed to investigate the efficacy of Qigong as a non-pharmacological treatment of hypertension and evaluate the contribution of Qigong in the blood pressure ( BP ) reduction of essential hypertension patients . Fifty-eight patients volunteered to participate in this study and were r and omly divided into either a Qigong group ( n = 29 ) , or a wait list control group ( n = 29 ) . In response to 10 weeks of Qigong , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and rate pressure product ( RPP ) were decreased significantly . There was a significant reduction of norepinephrine , epinephrine , cortisol , and stress level by the Qigong . These results suggest that Qigong may reduce BP and catecholamines via stabilizing the sympathetic nervous system . Therefore , Qigong is an effective nonpharmacological modality to reduce BP in essential hypertensive OBJECTIVE Twelve forms of Sun-style tai chi exercise have been developed specifically to reduce the symptoms and improve the physical functioning of arthritic patients , and this r and omized study examined the changes in symptoms and physical characteristics in older women with osteoarthritis ( OA ) at the completion of a 12-week tai chi exercise program . METHODS Seventy-two patients with OA were r and omly assigned into 2 groups . Due to a 41 % overall dropout rate , 22 experimental subjects and 21 controls completed pre- and post-test measures over a 12 week interval . Outcome variables were physical symptoms and fitness , body mass index , cardiovascular functioning , and perceived difficulties in physical functioning . The independent t test was used to examine group differences . RESULTS The homogeneity test confirmed that there were no significant group differences in demographic data and pretest measures . Mean comparisons of the change scores revealed that the experimental group perceived significantly less pain ( t = -2.19 , p = 0.034 ) and stiffness ( t = -2.13 , p = 0.039 ) in their joints , and reported fewer perceived difficulties in physical functioning ( t = -2.81 , p = 0.008 ) , while the control group showed no change or even deterioration in physical functioning after 12 weeks . In the physical fitness test , there were significant improvements in balance ( t = 3.34 , p = 0.002 ) and abdominal muscle strength ( t = 2.74 , p = 0.009 ) for the tai chi exercise group . No significant group differences were found in flexibility and upper-body or knee muscle strength in the post-test scores . CONCLUSION Older women with OA were able to safely perform the 12 forms of Sun-style tai chi exercise for 12 weeks , and this was effective in improving their arthritic symptoms , balance , and physical functioning . A longitudinal study with a larger sample size is now needed to confirm the potential use of tai chi exercise in arthritis management OBJECTIVE Yoga and relaxation techniques have traditionally been used by nonmedical practitioners to help alleviate musculoskeletal symptoms . The objective of this study was to collect controlled observations of the effect of yoga on the h and s of patients with osteoarthritis ( OA ) . METHODS Patients with OA of the h and s were r and omly assigned to receive either the yoga program or no therapy . Yoga techniques were supervised by one instructor once/week for 8 weeks . Variables assessed were pain , strength , motion , joint circumference , tenderness , and h and function using the Stanford H and Assessment question naire . RESULTS The yoga treated group improved significantly more than the control group in pain during activity , tenderness and finger range of motion . Other trends also favored the yoga program . CONCLUSION This yoga derived program was effective in providing relief in h and OA . Further studies are needed to compare this with other treatments and to examine longterm effects OBJECTIVE This study aim ed to assess the usefulness of two interventions in a group rehabilitation medicine setting to determine strategies and exercise guidelines for long-term care of the HIV/AIDS population with human immunodeficiency virus ( HIV ) and /or acquired immunodeficiency syndrome ( AIDS ) . DESIGN This was a r and omized clinical trial investigating the effects of tai chi ( TC ) and aerobic exercise ( EX ) on functional outcomes and quality of life ( QOL ) in patients with AIDS . SETTING Two outpatient infectious disease clinics in a mid-atlantic state were the setting . SUBJECTS AND INTERVENTION Thirty-eight ( 38 ) subjects with advanced HIV ( AIDS ) were r and omized to one of three groups : TC , EX , or control . Experimental groups exercised twice weekly for 8 weeks . OUTCOME MEASURES The primary outcomes included QOL as measured by the Medical Outcomes Short Form ( MOS-HIV ) and Spirituality Well-Being Scale ( SWB ) . Functional measures included the functional reach ( FR ) for balance , sit and reach ( SR ) for flexibility , and sit-up ( SU ) test for endurance . The physical performance test ( PPT ) was used to determine overall function , and the Profile of Mood States ( POMS ) was used to evaluate psychologic changes . To consider the patients ' explanations for these measurements , qualitative data were collected from subjects ' journals , focus groups , and nonparticipant observation . RESULTS Thirty-eight ( 38 ) subjects were included in data analysis : 13 in the TC group , 13 in the EX group , and 12 in the control group . Results of analysis of covariance showed significant changes in the exercise groups in overall functional measures ( p < 0.001 ) . The MOS-HIV showed a significant difference on the subscale of overall health ( p = 0.04 ) . The POMS showed significant main effect for time in confusion-bewilderment ( p = 0.000 ) and tension-anxiety ( p = 0.005 ) . Three dominant themes emerged from the qualitative data , including : positive physical changes , enhanced psychologic coping , and improved social interactions . CONCLUSIONS This study shows that TC and EX improve physiologic parameters , functional outcomes , and QOL . Group intervention provides a socialization context for management of chronic HIV disease . This study supports the need for more research investigating the effect of other types of group exercise for this population . This study sets the stage for a larger r and omized controlled trial to examine the potential short- and long-term effects of group exercise that may prove beneficial in the management of advanced HIV disease . Further research is warranted to evaluate additional exercise interventions that are accessible , safe , and cost-effective for the HIV population The present study investigates the effectiveness of Erikson hypnosis and Jacobson relaxation for the reduction of osteoarthritis pain . Participants reporting pain from hip or knee osteoarthritis were r and omly assigned to one of the following conditions : ( a ) hypnosis ( i.e. st and ardized eight-session hypnosis treatment ) ; ( b ) relaxation ( i.e. st and ardized eight sessions of Jacobson 's relaxation treatment ) ; ( c ) control ( i.e. waiting list ) . Overall , results show that the two experimental groups had a lower level of subjective pain than the control group and that the level of subjective pain decreased with time . An interaction effect between group treatment and time measurement was also observed in which beneficial effects of treatment appeared more rapidly for the hypnosis group . Results also show that hypnosis and relaxation are effective in reducing the amount of analgesic medication taken by participants . Finally , the present results suggest that individual differences in imagery moderate the effect of the psychological treatment at the 6 month follow-up but not at previous times of measurement ( i.e. after 4 weeks of treatment , after 8 weeks of treatment and at the 3 month follow-up ) . The results are interpreted in terms of psychological processes underlying hypnosis , and their implication s for the psychological treatment of pain are discussed Purpose . To evaluate the effect of a 7-week Qigong intervention on subjects with Fibromyalgia Syndrome ( FMS ) . Methods . The study was a controlled r and omized study with repeated measures . Fifty-seven FMS female subjects were r and omly assigned to an intervention group ( n = 29 ) or a waiting-list control group ( n = 28 ) . After completion of the experimental part , the control group received the same intervention . Collection of data was made at pre- and post-treatment and at 4-month follow-up for both groups . Results . During the experimental part of the study , significant improvements were found for the intervention group , at post-treatment , regarding different aspects of pain and psychological health and distress . Almost identical results were found for the combined group . At 4-month follow-up , the majority of these results were either maintained or improved . Conclusion . The overall results show that Qigong has positive and reliable effects regarding FMS . A high degree of completion , 93 % , and contentment with the intervention further support the potential of the treatment . The results of the study are encouraging and suggest that Qigong intervention could be a useful complement to medical treatment for subjects with FMS Study Design . The effectiveness and efficacy of Iyengar yoga for chronic low back pain ( CLBP ) were assessed with intention-to-treat and per- protocol analysis . Ninety subjects were r and omized to a yoga ( n = 43 ) or control group ( n = 47 ) receiving st and ard medical care . Participants were followed 6 months after completion of the intervention . Objective . This study aim ed to evaluate Iyengar yoga therapy on chronic low back pain . Yoga subjects were hypothesized to report greater reductions in functional disability , pain intensity , depression , and pain medication usage than controls . Summary of Background Data . CLBP is a musculoskeletal disorder with public health and economic impact . Pilot studies of yoga and back pain have reported significant changes in clinical ly important outcomes . Methods . Subjects were recruited through self-referral and health professional referrals according to explicit inclusion /exclusion criteria . Yoga subjects participated in 24 weeks of biweekly yoga classes design ed for CLBP . Outcomes were assessed at 12 ( midway ) , 24 ( immediately after ) , and 48 weeks ( 6-month follow-up ) after the start of the intervention using the Oswestry Disability Question naire , a Visual Analog Scale , the Beck Depression Inventory , and a pain medication-usage question naire . Results . Using intention-to-treat analysis with repeated measures ANOVA ( group × time ) , significantly greater reductions in functional disability and pain intensity were observed in the yoga group when compared to the control group at 24 weeks . A significantly greater proportion of yoga subjects also reported clinical improvements at both 12 and 24 weeks . In addition , depression was significantly lower in yoga subjects . Furthermore , while a reduction in pain medication occurred , this was comparable in both groups . When results were analyzed using per- protocol analysis , improvements were observed for all outcomes in the yoga group , including agreater trend for reduced pain medication usage . Although slightly less than at 24 weeks , the yoga group had statistically significant reductions in functional disability , pain intensity , and depression compared to st and ard medical care 6-months postintervention . Conclusion . Yoga improves functional disability , pain intensity , and depression in adults with CLBP . There was also a clinical ly important trend for the yoga group to reduce their pain medication usage compared to the control group BACKGROUND / AIMS Rheumatoid arthritis ( RA ) is a serious health problem result ing in significant morbidity and disability . Tai Chi may be beneficial to patients with RA as a result of effects on muscle strength and ' mind-body ' interactions . To obtain preliminary data on the effects of Tai Chi on RA , we conducted a pilot r and omized controlled trial . Twenty patients with functional class I or II RA were r and omly assigned to Tai Chi or attention control in twice-weekly sessions for 12 weeks . The American College of Rheumatology ( ACR ) 20 response criterion , functional capacity , health-related quality of life and the depression index were assessed . RESULTS At 12 weeks , 5/10 patients ( 50 % ) r and omized to Tai Chi achieved an ACR 20 % response compared with 0/10 ( 0 % ) in the control ( p = 0.03 ) . Tai Chi had greater improvement in the disability index ( p = 0.01 ) , vitality subscale of the Medical Outcome Study Short Form 36 ( p = 0.01 ) and the depression index ( p = 0.003 ) . Similar trends to improvement were also observed for disease activity , functional capacity and health-related quality of life . No adverse events were observed and no patients withdrew from the study . CONCLUSION Tai Chi appears safe and may be beneficial for functional class I or II RA . These promising results warrant further investigation into the potential complementary role of Tai Chi for treatment of RA |
12,467 | 20,838,825 | Prophylactic CSF administration reduces the time to neutrophil recovery and length of hospitalization , but has no impact on documented infections or outcome . | R and omized controlled trials ( RCT ) investigating administration of colony-stimulating factors ( CSF ) during or after chemotherapy in acute myeloid leukemia ( AML ) patients have not been systematic ally review ed . | The optimal induction for older adults with acute myeloid leukemia ( AML ) is unknown . Several anthracyclines have been proposed , but the data remain equivocal . Additionally , few prospect i ve trials of priming with hematopoietic growth factors to cycle leukemia cells prior to induction chemotherapy have been conducted . Three hundred and sixty-two older adults with previously untreated AML were r and omized to either daunorubicin , idarubicin or mitoxantrone with a st and ard dose of cytarabine as induction therapy . In addition , 245 patients were also r and omized to receive granulocyte-macrophage colony-stimulating factor ( GM-CSF ) or placebo beginning 2 days prior to induction chemotherapy and continuing until marrow aplasia . No difference was observed in the disease-free overall survival or in toxicity among patients receiving any of the 3 induction regimens or among those receiving growth factor or placebo for priming . However , the complete remission rate for the first 113 analyzable patients , who did not participate in the priming study and started induction therapy 3 to 5 days earlier than those who did , was significantly higher ( 50 % versus 38 % ; P = .03 ) . None of the anthracyclines is associated with improved outcome in older adults . Priming with hematopoietic growth factor did not improve response when compared with placebo . Furthermore , delaying induction therapy in older adults may lead to a lower complete remission rate The role of glycosylated recombinant human granulocyte colony-stimulating factor ( G-CSF ) in the induction treatment of older adults with acute myeloid leukemia ( AML ) is still uncertain . In this trial , a total of 722 patients with newly diagnosed AML , median age 68 years , were r and omized into 4 treatment arms : ( A ) no G-CSF ; ( B ) G-CSF during chemotherapy ; ( C ) G-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes ; and ( D ) G-CSF during and after chemotherapy . The complete remission ( CR ) rate was 48.9 % in group A , 52.2 % in group B , 48.3 % in group C , and 64.4 % in group D. Analysis according to the 2 x 2 factorial design indicated that the CR rate was significantly higher in patients who received G-CSF during chemotherapy ( 58.3 % for groups B + D vs 48.6 % for groups A + C ; P = .009 ) , whereas no significant difference was observed between groups A + B and C + D ( 50.6 % vs 56.4 % , P = .12 ) . In terms of overall survival , no significant differences were observed between the various groups . Patients who received G-CSF after chemotherapy had a shorter time to neutrophil recovery ( median , 20 vs 25 days ; P < .001 ) and a shorter hospitalization ( mean , 27.2 vs 29.7 days ; P < .001 ) . We conclude that although priming with G-CSF can improve the CR rate , the use of G-CSF during and /or after chemotherapy has no effect on the long-term outcome of AML in older patients Older age is a poor prognosis factor in acute myeloid leukemia ( AML ) . This double-blind trial was design ed to test the hypothesis that granulocyte colony-stimulating factor ( G-CSF ) used as supportive care could improve the treatment of elderly AML patients . Two hundred thirty-four patients 55 or more years of age with a morphologic diagnosis of de novo or secondary AML , French-American-British ( FAB ) M0-M7 , excluding M3 , were r and omly assigned to a st and ard induction regimen ( daunorubicin at 45 mg/m2 intravenously [ IV ] on days 1 through 3 and Ara-C at 200 mg/m2 IV continuous infusion on days 1 through 7 ) plus either placebo or G-CSF ( 400 microg/m2 IV over 30 minutes once daily ) . Results are reported here for 211 central ly confirmed cases of non-M3 AML . The two groups were well balanced in demographic , clinical , and hematological parameters , with median ages of 68 years in the G-CSF and 67 years in the placebo groups . The complete response ( CR ) rate was not significantly better in the G-CSF group : 50 % in the placebo and 41 % in the G-CSF group ( one-tailed P = .89 ) . Median overall survival was also similar , 9 months ( 95 % confidence interval [ CI ] , 7 to 10 months ) in the placebo and 6 months ( 95 % CI , 3 to 8 months ) in the G-CSF arms ( P = .71 ) . We found a significant 15 % reduction in the time to neutrophil recovery in the G-CSF group ( P = .014 ) . G-CSF had no impact on recovery from thrombocytopenia ( P = .80 ) or duration of first hospitalization ( P = .27 ) . When infection complications were evaluated , G-CSF had a beneficial effect on the duration but not on incidence of infection . G-CSF patients had fewer days with fever and shorter duration of antibiotic use . However , there was no difference in the frequency of total documented infections or in the number of fatal infections ( 19 % placebo v 20 % G-CSF ) . In this study of elderly AML patients , G-CSF improved clinical parameters of duration of neutropenia and antibiotic use , but did not change CR rate or survival or shorten hospitalization The role of granulocyte colony stimulating factor ( G‐CSF ) as supportive therapy following intensive induction chemotherapy for acute myeloid leukaemia ( AML ) in adults was investigated in a r and omized trial . G‐CSF ( Lenograstim , 263 μg/d ) or placebo was administered from day 8 after the end of chemotherapy until neutrophil recovery to 0·5 × 109/l ( or for up to 10 d ) . Eight hundred and three patients were entered . Neutrophil recovery was quicker with G‐CSF ( P < 0·0001 ) , but this did not lead to differences in the number , severity or duration of infections . There were no substantial supportive care savings , although G‐CSF patients spent 2 d less in hospital ( P = 0·01 ) . Complete remission ( CR ) rates were similar between arms ( 73 % G‐CSF , 75 % placebo , P = 0·5 ) , as were reasons for failure ( induction death : P = 0·7 ; resistant disease : P = 0·5 ) and , for remitters , 5‐year disease‐free survival ( 34 % vs. 38 % , P = 0·3 ) . Overall survival at 5 years was 29 % with G‐CSF vs. 36 % with placebo ( P = 0·10 ) . Both CR rate ( P = 0·006 ) and overall survival ( P = 0·006 ) were worse with G‐CSF in patients aged < 40 years , but this may be a chance effect . There is some evidence from this trial of an adverse effect of G‐CSF but these data need to be viewed in the context of the evidence from the other trials A r and omized treated/non-treated study of rG.CSF ( 5 micrograms/kg/d , d.i.v . ) in patients with acute myelogenous leukemia was conducted to assess its efficacy on fever ( > or = 38 degrees C ) or documented infection after induction therapy . Of 95 patients enrolled , 46 patients were evaluable for safety and 43 for efficacy in the treated group of 47 patients while 37 of 48 patients were eligible for data analysis in the untreated group . Mare patients showed a recovery in the blood neutrophil count ( to > 1,000/microliters ) during rG.CSF treatment ( 14 days ) than in the non-treated group ( p = 0.039 ) while the number of febrile patients and duration of fever did not significantly differ between the two groups . The treatment with rG.CSF enabled an early recovery in neutrophil count in the patients with neutropenia and overt signs of infection after induction therapy , but there was no hastened allevistion of symptoms of infection in these patients Pre clinical data suggest that retinoids , eg , all-trans retinoic acid ( ATRA ) , lower concentrations of antiapoptotic proteins such as bcl-2 , possibly thereby improving the outcome of anti-acute myeloid leukemia ( AML ) chemotherapy . Granulocyte colony-stimulating factor ( G-CSF ) has been considered to be potentially synergistic with ATRA in this regard . Accordingly , we r and omized 215 patients with newly diagnosed AML ( 153 patients ) or high-risk myelodysplastic syndrome ( MDS ) ( refractory anemia with excess blasts [ RAEB ] or RAEB-t , 62 patients ) to receive fludarabine + ara-C + idarubicin ( FAI ) alone , FAI + ATRA , FAI + G-CSF , or FAI + ATRA + G-CSF . Eligibility required one of the following : age over 71 years , a history of abnormal blood counts before M.D. And erson ( MDA ) presentation , secondary AML/MDS , failure to respond to one prior course of chemotherapy given outside MDA , or abnormal renal or hepatic function . For the two treatment arms containing ATRA , ATRA was given 2 days ( day-2 ) before beginning and continued for 3 days after completion of FAI . For the two treatment arms including G-CSF , G-CSF began on day-1 and continued until neutrophil recovery . Patients with white blood cell ( WBC ) counts > 50,000/microL began ATRA on day 1 and G-CSF on day 2 . Events ( death , failure to achieve complete remission [ CR ] , or relapse from CR ) have occurred in 77 % of the 215 patients . Reflecting the poor prognosis of the patients entered , the CR rate was only 51 % , median event-free survival ( EFS ) time once in CR was 36 weeks , and median survival time was 28 weeks . A Cox regression analysis indicated that , after accounting for patient prognostic variables , none of the three adjuvant treatment combinations ( FAI + ATRA , FAI + G , FAI + ATRA + G ) affected survival , EFS , or EFS once in CR compared with FAI . Similarly , there were no significant effects of either ATRA ignoring G-CSF , or of G-CSF ignoring ATRA . As previously found , a diagnosis of RAEB or RAEB-t rather than AML was insignificant . There were no indications that the effect of ATRA differed according to cytogenetic group , diagnosis ( AML or MDS ) , or treatment schedule . Logistic regression analysis indicated that , after accounting for prognosis , addition of G-CSF + /- ATRA to FAI improved CR rate versus either FAI or FAI + ATRA , but G-CSF had no effect on the other outcomes . We conclude that addition of ATRA + /- G-CSF to FAI had no effect on CR rate , survival , EFS , or EFS in CR in poor prognosis , newly diagnosed AML or high-risk MDS The optimum chemotherapy schedule for reinduction of patients with high-risk acute myeloid leukemia ( relapsed , resistant/refractory , or adverse genetic disease ) is uncertain . The MRC AML ( Medical Research Council Acute Myeloid Leukemia ) Working Group design ed a trial comparing fludarabine and high-dose cytosine ( FLA ) with st and ard chemotherapy comprising cytosine arabinoside , daunorubicin , and etoposide ( ADE ) . Patients were also r and omly assigned to receive filgrastim ( G-CSF ) from day 0 until neutrophil count was greater than 0.5 x 10(9)/L ( or for a maximum of 28 days ) and all-trans retinoic acid ( ATRA ) for 90 days . Between 1998 and 2003 , 405 patients were entered : 250 were r and omly assigned between FLA and ADE ; 356 to G-CSF versus no G-CSF ; 362 to ATRA versus no ATRA . The complete remission rate was 61 % with 4-year disease-free survival of 29 % . There were no significant differences in the CR rate , deaths in CR , relapse rate , or DFS between ADE and FLA , although survival at 4 years was worse with FLA ( 16 % versus 27 % , P = .05 ) . Neither the addition of ATRA nor G-CSF demonstrated any differences in the CR rate , relapse rate , DFS , or overall survival between the groups . In conclusion these findings indicate that FLA may be inferior to st and ard chemotherapy in high-risk AML and that the outcome is not improved with the addition of either G-CSF or ATRA Summary . To investigate the efficacy and safety of granulocyte colony‐stimulating factor ( G‐CSF ) in patients with acute myelogenous leukaemia , a multicentre r and omized study was performed . From October 1993 to September 1996 , 270 patients with newly diagnosed acute myelogenous leukaemia were r and omized to G‐CSF or control groups after remission induction therapy . The G‐CSF group received G‐CSF ( Filgrastim ) from 48 h after the completing chemotherapy until the absolute neutrophil count exceeded 1·5 × 109/l . The control group did not receive G‐CSF unless severe infection occurred . There were 245 evaluable patients ( 120 and 125 in the G‐CSF and control groups respectively ) . The complete remission rate was similar in the G‐CSF and control groups ( 80·8 % versus 76·8 % ) , as was the 5‐year probability of disease‐free survival ( 34·5 % versus 33·6 % ) and overall survival ( 42·7 % versus 35·6 % ) . Neutrophil recovery was significantly faster in the G‐CSF group than in the control group ( 12 d versus 18 d , P = 0·0001 ) . The median duration of febrile neutropenia was significantly shorter in the G‐CSF group than in the control group ( 3 d versus 4 d , P = 0·0001 ) . In conclusion , prophylactic administration of G‐CSF after remission induction therapy for acute myelogenous leukaemia is safe and useful even in patients without infection on completing chemotherapy A total of 110 patients , aged 64 years or over , with de novo acute myeloid leukaemia ( AML ) and white blood cell counts < 50 × 109/l were treated with 3 d of cytarabine 1 g/m2 twice daily , mitoxantrone 12 mg/m2 and etoposide 200 mg/m2 , r and omized with or without the addition of granulocyte‐macrophage colony‐stimulating factor ( GM‐CSF ) 200 μg/m2 . The primary aim was to evaluate the effect of GM‐CSF on the remission rate . Secondary aims included comparison of duration of remission , survival and infectious complications and the impact of maintenance therapy with thioguanine . Complete remission ( CR ) was achieved by 64 % of patients without GM‐CSF , and by 65 % of patients who received GM‐CSF , the median remission duration was 13 vs. 6 months , the median overall survival ( OS ) was 14 vs. 9 months , the mean time to neutrophil recovery was 25 vs. 17 d ( P = 0·03 ) and the number of positive blood cultures was 46 vs. 39 ( P = 0·05 ) respectively . The impact of thioguanine remains unanswered since only 30 patients remained in CR after consolidation therapy . We conclude that induction therapy is feasible with acceptable toxicity in elderly patients with AML , albeit with a high relapse rate and short OS . GM‐CSF prior to , and in combination with , induction treatment reduced the time to neutrophil recovery and the number of neutropenic septicaemia cases but did not improve the OS of AML in the elderly PURPOSE To assess the value of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) for induction treatment of acute myeloid leukemia ( AML ) , both for priming of leukemic cells and for acceleration of hematopoietic recovery . PATIENTS AND METHODS GM-CSF was administered 5 micrograms/kg/d by continuous intravenous ( i.v . ) infusion during induction therapy with daunorubicin ( DNR ) ( days 1 to 3 ) and cytarabine ( ARA-C ) ( days 1 to 7 ) . A total of 102 patients were r and omized onto four arms , as follows : ( 1 ) GM-CSF 24 hours before and during chemotherapy ( arm + /- ) ; ( 2 ) GM-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes ( PMNs ) ( arm -/+);(3 ) GM-CSF before , during , and after chemotherapy ( arm + /+ ) ; or ( 4 ) no GM-CSF ( arm -/- ) . Stopping rules were applied in case of an initial WBC count greater than 30 x 10(9)/L or a secondary increase of circulating blast cells . Analyses were performed according to the intention-to-treat principle . RESULTS The complete remission ( CR ) rates were 77 % ( arm -/- ) , 72 % ( arm + /- ) , 48 % ( arm -/+ ) , and 46 % ( arm + /+ ) . Patients r and omized to receive GM-CSF after induction ( arms -/+ and + /+ ) had a significantly lower CR rate ( P = .008 ) and a trend toward accelerated recovery of neutrophils , but no fewer infections or induction deaths . The lower CR rate appeared to be related to an increased resistance rate , with persistent leukemia . The main side effects of GM-CSF were fluid retention and hypotension . CONCLUSION GM-CSF administered during induction treatment of AML with a DNR/Ara-C combination did not provide any clinical benefit . Furthermore , there was a significant decrease in the CR rate with more persistent leukemia when GM-CSF was administered during the hypoplastic phase after the chemotherapy courses The Australian Leukaemia Study Group ( ALSG ) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia ( AML ) intensified with high-dose cytarabine , and therefore improve response rates and survival . Patients were r and omised to receive lenograstim ( glycosylated recombinant human G-CSF ) 5 μg per kg body weight subcutaneously daily from day 8 after starting chemotherapy , or no cytokine , following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1 , 3 , 5 , and 7 , together with idarubicin 9 or 12 mg/m2 on days 1 , 2 , and 3 , plus etoposide 75 mg/m2 on days 1 to 7 inclusive . Patients had untreated AML , and were aged 16 to 60 years . Overall , 54 evaluable patients were r and omised to receive lenograstim and 58 to no cytokine . Patients in the lenograstim arm had a significantly shorter duration of neutropenia < 0.5 × 109/l compared to patients in the no cytokine arm ( median 18 vs 22 days ; P = 0.0005 ) , and also shorter duration of total leucopenia < 1.0 × 109/l ( 17 vs 19 days ; P = 0.0002 ) , as well as a reduction in duration of treatment with therapeutic intravenous antibiotics ( 20 vs 24 days ; P = 0.015 ) and a trend to reduced number of days with fever > 38.0 ° C ( 9 vs 12 days ; P = 0.18 ) . There were no differences between the two groups in platelet recovery , red cell or platelet transfusions , or non-haematological toxicities . For patients achieving CR after their first induction course , a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm , from a median of 40.5 days to a median of 36 days ( P = 0.082 ) . The overall complete response rates to chemotherapy were similar , 81 % in the lenograstim arm vs 75 % for the no cytokine arm ( P = 0.5 ) , and there was no significant difference in the survival duration s. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine , result ing in an improvement in a number of clinical ly important parameters with no major adverse effects In this prospect i ve r and omized multicenter trial 93 patients , median age 72 years , with RAEB-t ( n=25 ) and myelodysplastic syndrome (MDS)-AML ( n=68 ) were allocated to a st and ard induction chemotherapy regimen ( TAD 2 + 7 ) with or without addition of granulocyte – macrophage-CSF ( GM-CSF ) . The overall complete remission ( CR ) rate was 43 % with no difference between the arms . Median survival times for all patients , CR patients , and non-CR patients were 280 , 550 , and 100 days , respectively , with no difference between the arms . Response rates were significantly better in patients with serum lactate dehydrogenase ( S-LDH ) levels ⩽9.5 μkat/l , bone marrow cellularity ⩽70 % , and WBC counts < 4.0 × 109/l , but S-LDH was the only variable independently associated with response by logistic regression analysis . Cox 's regression analysis identified four significant prognostic factors for survival : bone marrow cellularity , S-LDH , cytogenetic risk group ( International Prognostic Scoring System ) , and age . Only bone marrow cellularity ( P=0.01 ) and S-LDH ( P=0.0003 ) retained statistical significance in the log-rank test . Severe adverse events were significantly more common in the GM-TAD arm ( P=0.01 ) . Thus , addition of GM-CSF to chemotherapy showed no clinical benefit in terms of response but carried an increased risk for side effects . We present a clinical ly useful tool to predict response to chemotherapy and survival in elderly patients with transforming MDS , favoring patients with features of less proliferative disease The treatment of adult patients greater than 55 to 70 years of age with acute myelogenous leukemia ( AML ) is associated with a treatment-related mortality of approximately 25 % . This prospect i ve , double-blind r and omized study was design ed to see if the use of granulocyte-macrophage colony stimulating factor ( GM-CSF ; yeast-derived ) could shorten the period of neutropenia and to determine any effect this would have on therapy-related morbidity and mortality . A total of 124 patients entered this study . Induction consisted of st and ard daunorubicin and cytarabine . A day-10 bone marrow was examined ; if this was aplastic without leukemia , patients received blinded placebo or GM-CSF from day 11 until neutrophil recovery . Patients who entered complete remission received the identical study medication ( blinded GM-CSF or placebo ) in consolidation that they had received during induction . The overall complete remission rate was 52 % ; 60 % for the GM-CSF arm and 44 % for the placebo arm ( P = .08 ) . Median times to neutrophil recovery were significantly shortened on the GM-CSF arm . The overall treatment-related toxicity from start of GM-CSF/placebo was reduced on the GM-CSF arm ( P = .049 ) . Similarly , the infectious toxicity was significantly reduced on the GM-CSF arm ( P = .015 ) . The median survival for all patients was 10.6 months in the GM-CSF group and 4.8 months in the placebo arm ( P = .048 ) . It appears that GM-CSF is safe and efficacious for adult patients greater than 55 to 70 years of age with AML ; its major impact is in reducing the duration of neutropenia and therapy-related mortality and morbidity . This may result in a better response rate The safety and efficacy of filgrastim as an adjunct to acute myeloid leukemia ( AML ) induction and consolidation therapy was assessed in this prospect i ve double-blind , r and omized , placebo-controlled , multicenter trial . A total of 521 consecutive de novo AML patients aged 16 or more years were r and omized to receive filgrastim ( 5 microg/kg/d subcutaneously ) or placebo after st and ard induction as well as consolidation chemotherapy . Blinded study drug was given from 24 hours after chemotherapy until the absolute neutrophil count was > /=1.0 x 10(9)/L for 3 consecutive days . The overall complete remission rate was 68 % . After a median follow-up of 24 months ( range 5 to 40 ) the median disease-free survival was 10 months ( 95 % confidence interval [ CI ] , 8.7 to 10.8 ) and the median overall survival was 13 months ( 95%CI , 12.2 to 14.6 ) . These did not differ between treatment groups . Patients receiving filgrastim experienced neutrophil recovery 5 days earlier after induction 1 than those receiving placebo ( P < .0001 ) . This was accompanied by reductions in the duration of fever ( 7 v 8.5 days ; P = .009 ) , parenteral antibiotic use ( 15 v 18.5 days ; P = .0001 ) , and hospitalization ( 20 v 25 days ; P = .0001 ) . Similar reductions were seen after induction 2 and the consolidation courses . There was a significant reduction in the number of patients requiring systemic antifungal therapy in the filgrastim group during induction treatment ( 34 % v 43 % ; P = .04 ) . In conclusion , filgrastim is safe in that it had no negative impact on the prognosis of the AML patients . In addition , it effectively reduced the duration of neutropenia , leading to significant clinical benefits by reducing the duration of fever ; requirement for parenteral anti-infectives , specifically amphotericin B ; and the duration of hospitalization We previously reported the results of a double-blind , placebo-controlled study of Filgrastim in patients with de novo AML undergoing induction and consolidation chemotherapy . The study demonstrated that Filgrastim was effective and well tolerated and had no impact on complete remission or survival . We now report follow-up data on these patients , assessing long-term effects with emphasis on prognostic indicators . After a median follow-up of 7 years , 434 ( 83 % ) patients were dead , 73 ( 14 % ) were alive , and 14 ( 3 % ) were lost to follow-up . The proportions of deaths were similar in the Filgrastim ( 83 % ) and placebo ( 84 % ) groups . No differences in median time to death ( 1.04 years Filgrastim , 1.13 years placebo ; P=0.97 ) or median disease-free survival ( 0.86 years Filgrastim , 0.79 years placebo ; P=0.52 ) were evident . Proportional hazard modeling identified age , performance status , and French-American-British subtype as independent predictors for survival ( P<0.001 , P=0.005 , and P=0.036 , respectively ) , whereas cytogenetic status was not ( P=0.118 ) . Filgrastim had no effect on overall survival in any of these subgroup analyses as none of the treatment comparisons were statistically significant . These findings indicate that Filgrastim can be effectively used to support patients with AML undergoing induction and consolidation chemotherapy without worsening long-term disease outcome A multicenter , r and omized , double-blind controlled study was performed to evaluate the efficacy and safety of recombinant human granulocyte colony-stimulating factor ( rG.CSF ) in reducing infectious morbidity and neutropenia induced by consolidation chemotherapy for acute myeloid leukemia ( AML ) . One hundred and twenty-four eligible patients were r and omized to receive either rG.CSF ( 5 micrograms/kg/d d.i.v . ; 59 patients ) or placebo ( 65 patients ) for 14 days from the day after chemotherapy . All of them were included in the safety analysis , while 57 patients receiving rG.CSF and 64 patients receiving placebo were included in the efficacy analysis . The duration of neutropenia as well as the incidence of fever and febrile neutropenia , and frequency of antibiotic therapy required , were all significantly reduced in the rG.CSF group . No serious adverse reactions were encountered ; there was no significant difference between the two groups in terms of incidence of adverse events . These results demonstrate that rG.CSF is beneficial to alleviate neutropenic episodes induced by consolidation chemotherapy in patients with AML BACKGROUND Intensive chemotherapy for acute myelogenous leukemia ( AML ) continues to yield low rates of complete remission and survival among patients over the age of 65 years . Infection-related mortality is particularly high among these patients during the period of neutropenia that follows chemotherapy . We determined the effect of lenograstim ( glycosylated recombinant human granulocyte colony-stimulating factor ) on mortality at eight weeks ( the main end point ) and the rate of complete remission among patients with AML who were 65 years old or older . METHODS After induction chemotherapy with daunorubicin ( 45 mg per square meter of body-surface area per day for 4 days ) and cytarabine arabinoside ( 200 mg per square meter per day for 7 days ) , 173 patients with newly diagnosed AML were r and omly assigned on day 8 to receive either lenograstim ( 5 micrograms per kilogram of body weight per day ) or placebo , starting on day 9 , until there was neutrophil recovery or a treatment failure , or for a maximum of 28 days . Salvage chemotherapy was also followed by lenograstim or placebo . Patients with a complete remission received two consolidation courses of chemotherapy without lenograstim or placebo . RESULTS The mortality rate at eight weeks was similar in the lenograstim and placebo groups ( 23 and 27 percent , respectively ; P = 0.60 ) , as was the incidence of severe infections . The median duration of neutropenia ( absolute neutrophil count < or = 1000 per cubic millimeter ) was shorter in the lenograstim group ( 21 days , as compared with 27 days in the placebo group ; P < 0.001 ) . Eight percent of the patients in both groups had regrowth of AML cells . The rate of complete remission was significantly higher in the lenograstim group ( 70 percent , as compared with 47 percent in the placebo group ; P = 0.002 ) . Overall survival , however , was similar in the two groups ( P = 0.76 ) . CONCLUSIONS The administration of lenograstim after chemotherapy for AML did not decrease the mortality rate at eight weeks among patients over the age of 65 years . The patients who received lenograstim had a significantly higher rate of complete remission than those who received placebo . Nevertheless , the overall survival in the two groups did not differ significantly PURPOSE Ten years after the first clinical studies , the clinical impact of myeloid growth factors in acute myeloid leukemia is still unclear . One of the objectives of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques ( GOELAM ) 2 trial was to evaluate the benefit of granulocyte colony-stimulating factor ( GCSF ) given only after the two courses of intensive consolidation chemotherapy ( ICC ) used to maintain complete remission ( CR ) . PATIENTS AND METHODS One hundred ninety-four patients who were in CR after induction treatment were r and omly assigned to receive G-CSF ( 100 patients ) or no G-CSF ( 94 patients ) after two courses of ICC ( ICC 1 , high-dose cytarabine plus mitoxantrone ; ICC 2 , amsacrine plus etoposide ) . G-CSF ( filgrastim ) was administered from the day after chemotherapy until granulocyte recovery at a daily dose of 5 microg/kg . RESULTS In the G-CSF group , the median duration of neutropenia ( < 0.5 x 10(9)/L ) was dramatically reduced , both after ICC 1 ( 12 v 19 days , P < .001 ) and after ICC 2 ( 20 v 28 days , P < .001 ) . The median duration of hospitalization was also significantly shorter in the G-CSF group ( 24 v 27 days after ICC 1 , P < .001 ; 29 v 34 days after ICC 2 , P < . 001 ) . The median duration of intravenous antibiotics was significantly reduced after ICC 1 and ICC 2 , and the median duration of antifungal therapy was significantly reduced after ICC 1 . However , the incidence of microbiologically documented infections , the toxic death rate , the 2-year disease-free survival , and the 2-year overall survival were not affected by G-CSF administration . Moreover , the median interval between ICC1 and ICC2 was reduced by only 2 days , and the number of patients undergoing ICC2 was not increased in the G-CSF arm . CONCLUSION G-CSF should be administered routinely after ICC to reduce the duration of neutropenia and hospitalization . However , G-CSF did not seem to significantly increase the feasibility of this two-course program or modify overall outcome BACKGROUND Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia ( AML ) . METHODS In a multicenter r and omized trial , we assigned patients ( age range , 18 to 60 years ) with newly diagnosed AML to receive cytarabine plus idarubicin ( cycle 1 ) and cytarabine plus amsacrin ( cycle 2 ) with granulocyte colony-stimulating factor ( G-CSF ) ( 321 patients ) or without G-CSF ( 319 ) . G-CSF was given concurrently with chemotherapy only . Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect . The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups . RESULTS After induction chemotherapy , the rates of response were not significantly different in the two groups . After a median follow-up of 55 months , patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF ( 42 percent vs. 33 percent at four years , P=0.02 ) , owing to a reduced probability of relapse ( relative risk , 0.77 ; 95 percent confidence interval , 0.61 to 0.99 ; P=0.04 ) . G-CSF did not significantly improve overall survival ( P=0.16 ) . Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis , the 72 percent of patients with st and ard-risk AML benefited from G-CSF therapy ( overall survival at four years , 45 percent , as compared with 35 percent in the group that did not receive G-CSF [ relative risk of death , 0.75 ; 95 percent confidence interval , 0.59 to 0.95 ; P=0.02 ] ; disease-free survival , 45 percent vs. 33 percent [ relative risk , 0.70 ] ; 95 percent confidence interval , 0.55 to 0.90 ; P=0.006 ) . CONCLUSIONS Sensitization of leukemic cells with growth factors is a clinical ly applicable means of enhancing the efficacy of chemotherapy in patients with AML In a multicenter trial , 259 young adults ( 15–49 years ) with newly diagnosed acute myeloid leukemia ( AML ) were first r and omized to receive a timed-sequential induction regimen given either alone ( 135 patients ) or concomitantly with granulocyte – macrophage colony-stimulating factor ( GM-CSF ) ( 124 patients ) . Patients reaching complete remission ( CR ) were then r and omized to compare a timed-sequential consolidation to a postremission chemotherapy including four cycles of high-dose cytarabine followed by maintenance courses . In the appropriate arm , GM-CSF was given concurrently with chemotherapy during all cycles of consolidation . CR rates were significantly better in the GM-CSF arm ( 88 vs 78 % , P<0.04 ) , but did not differ after salvage . Patients receiving GM-CSF had a higher 3-year event-free survival ( EFS ) estimate ( 42 vs 34 % ) , but GM-CSF did not impact on overall survival . Patients with intermediate-risk cytogenetics benefited more from GM-CSF therapy ( P=0.05 ) in terms of EFS than patients with other cytogenetics . This was also confirmed when considering only patients following the second r and omization , or subgroups defined by a prognostic index based on cytogenetics and the number of courses required for achieving CR . Priming of leukemic cells with hematopoietic growth factors is a means of enhancing the efficacy of chemotherapy in younger adults with AML We investigated whether GM-CSF given concomitantly with chemotherapy ( CT ) and thereafter , improves the outcome of adults with de novo AML by increasing the efficacy of CT and reducing infections . CT included Ara-C , daunorubicin and etoposide ( DAV ) for induction and early consolidation therapy and one cycle with high-dose ( patients aged < or = 50 years ) or intermediate dose Ara-C ( patients aged > 50 years)/daunorubicin for late consolidation therapy . Eight patients were r and omized after DAVI to receive either GM-CSF ( E. coli , 250 micrograms/m2/day , s.c . ) or placebo starting 48 h prior to DAVII and the subsequent courses and given throughout CT until the absolute neutrophil count had recovered to > 500/microliters . The CR rate was 81 % in the GM-CSF and 79 % in the placebo group ( p = 0.57 ; Fisher 's exact test ) . The probability of relapse-free survival at 41 months after a median follow-up of 35 months was 42 % in the GM-CSF and 41 % in the placebo group ( p = 0.89 ; log rank test ) . GM-CSF did not shorten the period of neutropenia < or = 500/microliters , while it prolonged the duration of thrombocytopenia < or = 25,000/microliters . The incidence and severity of infections as well as the non-hematological toxicity were similar in both groups . In summary , in this r and omized trial GM-CSF as an adjunct to AML therapy was feasible . For the present GM-CSF does not have a significant effect on treatment outcome PURPOSE The hematopoietic growth factors ( HGFs ) introduced into induction chemotherapy ( CT ) of acute myeloid leukemia ( AML ) might be of benefit to treatment outcome by at least two mechanisms . HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT . HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality . MATERIAL S AND METHODS We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor ( GM-CSF ; 5 microg/kg ) in a prospect i ve r and omized study of factorial design ( yes or no GM-CSF during CT , and yes or no GM-CSF after CT ) in patients aged 15 to 60 years ( mean , 42 ) with newly diagnosed AML . GM-CSF was applied as follows : during CT only ( + /- , n = 64 assessable patients ) , GM-CSF during and following CT ( + /+ , n = 66 ) , no GM-CSF ( -/- , n = 63 ) , or GM-CSF after CT only ( -/+ , n = 60 ) . RESULTS The complete response ( CR ) rate was 77 % . At a median follow-up time of 42 months , probabilities of overall survival ( OS ) and disease-free survival ( DFS ) at 3 years were 38 % and 37 % in all patients . CR rates , OS , and DFS did not differ between the treatment groups ( intention-to-treat analysis ) . Neutrophil recovery ( 1.0 x 10(9)/L ) and monocyte recovery were significantly faster in patients who received GM-CSF after CT ( 26 days v 30 days ; neutrophils , P < .001 ; monocytes , P < .005 ) . Platelet regeneration , transfusion requirements , use of antibiotics , frequency of infections , and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities . More frequent side effects ( eg , fever and fluid retention ) were noted in GM-CSF-treated patients predominantly related to the use of GM-CSF during CT . CONCLUSION Priming of AML cells to the cytotoxic effects of CT by the use of GM-CSF during CT or accelerating myeloid recovery by the use of GM-CSF after CT does not significantly improve treatment outcome of young and middle-aged adults with newly diagnosed AML |
12,468 | 20,091,544 | The titration ( low dose ) regimen had fewer adverse effects than the block-replace ( high dose ) regimen and was no less effective .
Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism . | BACKGROUND Antithyroid drugs are widely used in the therapy of hyperthyroidism .
There are wide variations in the dose , regimen or duration of treatment used by health professionals .
OBJECTIVES To assess the effects of dose , regimen and duration of antithyroid drug therapy for Graves ' hyperthyroidism . | BACKGROUND The effect of supplementation with a fixed combination of antioxidants ( vitamins C and E , beta-carotene and selenium ) was monitored on the speed of attaining euthyroidism in a group of patients with Graves ' disease , treated with methimazole . METHODS The activity of glutathione peroxidase in whole blood and the concentrations of selenium , pituitary and thyroid hormones in serum were measured , prior to commencement of therapy and after 30 and 60 days . RESULTS Patients who received supplementation with antioxidants in addition to therapy with methimazole ( Group A , n=29 ) attained euthyroidism faster than the patients treated with only methimazole ( Group B , n=28 ) . The concentration of selenium in the serum of patients in Group A increased significantly during treatment ( p<0.001 ) , while there was no statistically significant change in the patients in Group B. The concentration of selenium in the serum between the groups differed statistically significantly 30 days ( p<0.05 ) and 60 days ( p<0.01 ) after the commencement of therapy . Activity of glutathione peroxidase in whole blood increased during treatment in both groups of patients . However , a statistically more significant increase occurred in Group A compared to Group B , 30 days after the commencement of therapy ( p<0.01 ) . CONCLUSION The results of the study clearly indicate that supplementation with antioxidants in the treatment of Graves ' disease is justified , particularly those containing selenium We compared the effects of high and low dosages of antithyroid drugs in 113 patients with Graves ' hyperthyroidism . The patients were r and omly divided into 2 groups . In group A , 65 patients received either methimazole ( MMI ) : 60 + /- 14.5 mg/day ( mean + /- SD ) ; range 40 - 100 mg/day , or propylthiouracil ( PTU ) : 693 + /- 173 mg/day ; range 500 - 1200 mg/day . These high doses were maintained throughout treatment with later addition of 50 - 75 micrograms T3 daily . Forty eight patients ( group B ) were treated with lower doses of MMI or PTU without thyroid hormone addition . The maintenance dose of MMI was 13.6 + /- 7 mg/day ( range 5 - 25 mg/day ) and that of PTU was 180 + /- 58 mg/day ( range 100 - 300 mg/day ) . The treatment period was 15.1 + /- 4.2 ( range 10 - 30 ) months for group A and 13.5 + /- 2.2 ( range 12 - 20 ) months for group B. Remission occurred in 75.4 % patients from group A and in 41.6 % patients from group B ( P less than 0.001 ) . The mean follow-up was 42 + /- 14 months ( 17 - 81 months ) . The free T4 index ( FT4I ) in group A remained below the normal range during treatment . The mean FT4I , obtained during the course of treatment , of patients who went into remission from group A was significantly ( P less than 0.001 ) lower than in relapsed patients ( 4.8 vs. 6.5 ) . Moreover , there was an inverse correlation between mean FT4I and maintenance daily dose of either MMI ( r = -0.567 ; P less than 0.001 ) , or PTU ( r = -0.379 ; P less than 0.01 ) . A fall in microsomal antibody ( MCHA ) titer occurred mainly in remission patients , and was more significant ( P less than 0.05 ) in group A patients . In contrast , 11 ( 7 from group B ) of the 16 patients with an increase of microsomal antibody levels relapsed . The frequency of negative tests of thyroid-stimulating antibody was higher in group A patients ( 71 % ) than in group B ( 29 % ) at the end of therapy ( P less than 0.01 ) . No correlation was found between thyroid T3 suppressibility and either mean FT4I or thyroid-stimulatory antibody activity during treatment . Our findings show that patients treated with high doses of PTU or MMI throughout treatment have a higher remission rate when compared to those treated with a more conventional regimen . These results support the hypothesis that large antithyroid drug doses may have greater immunosuppressive effects than low dosage regimens . Furthermore , a high dosage regimen could permit the restoration of the immune surveillance mechanisms and , thus , lasting remission of Graves ' disease UNLABELLED Graves ' disease ( GD ) patients treated with antithyroid drugs ( ATD ) have overall relapse rates of 30 - 50 % after ATD discontinuation . Conflicting data have been reported with regard to the usefulness of adding thyroxine ( I-T4 ) during and after ATD treatment . Also , clinicians are still in search of useful factors to predict remission/recurrence after ATD withdrawal . Eighty two consecutive patients were treated with ATD for 15 months , combined with 12 months of I-T4 . Then , patients were r and omized ( placebo-controlled double blind protocol ) to continuing I-T4 versus a placebo for one year . RESULTS I-T4 administration during and after ATD treatment did not affect favorably the outcome , the final recurrence rate being 31 % , in both placebo and I-T4 groups . Two factors were identified as independent and synergistic markers of a significantly increased risk of recurrence after ATD withdrawal : smoking and TSH receptor antibodies ( TSHR-Ab ) remaining positive at the end of ATD . Non smoking patients with a negative TSHR-Ab ( end ATD ) had a low ( 18 % ) recurrence risk , while smoking patients also with a negative TSHR-Ab had a higher ( 57 % ) recurrence risk . Non smoking patients with a positive TSHR-Ab ( end ATD ) had a 86 % recurrence risk . Finally , smoking patients with a positive TSHR-Ab ( end ATD ) all recurred within 6 months . CONCLUSIONS 1 ) T4 administration after ATD withdrawal does not improve recurrence rates ; 2 ) two parameters , smoking and positive TSHR-Ab ( at end ATD ) , were valid -- albeit not absolute-predictors of the risk of recurrence in ATD-treated patients with Graves ' disease BACKGROUND Antithyroid drugs are effective in patients with hyperthyroidism due to Graves ' disease , but the rate of recurrence after treatment is high . In a recent Japanese study , adjunctive treatment with thyroxine ( T4 ) was associated with a recurrence rate 20 times lower than that among patients who received only an antithyroid drug . If these results are confirmed , combined therapy with an antithyroid drug and T4 might become the treatment of choice for all patients with Graves ' hyperthyroidism . METHODS We treated 111 patients ( 89 women and 22 men ) who had Graves ' hyperthyroidism . All patients initially received 40 mg of carbimazole daily for one month . Then one group received carbimazole alone for 17 months ( 52 patients ) , and the other group received carbimazole plus T4 for 17 months and T4 alone for 18 months ( 59 patients ) . In the carbimazole group , the dose was adjusted after one month to maintain a normal serum thyrotropin concentration . In the carbimazole-T4 group , the dose of carbimazole was not changed , but 100 micrograms of T4 per day was added to the regimen and the dose was adjusted to maintain an undetectable serum thyrotropin concentration ( < 0.04 microU per milliliter ) . RESULTS At the time of our analysis , 53 of the 111 patients had completed at least 3 months of follow-up ( median , 12 months ) after carbimazole was withdrawn . Hyperthyroidism recurred in eight patients in each group after a mean ( + /- SD ) of 6 + /- 4 months in the carbimazole group and 7 + /- 4 months in the carbimazole-T4 group . There was no difference between the recurrence rates in the two groups , despite the fact that serum thyrotropin concentrations were undetectable in 73 percent of patients in the carbimazole-T4 group on at least 75 percent of their visits . CONCLUSIONS The administration of T4 to patients with Graves ' disease during carbimazole treatment and after its withdrawal neither delays nor prevents the recurrence of hyperthyroidism OBJECTIVE In Graves ' hyperthyroidism treated with antithyroid drugs ( ATD ) , the overall relapse rate reaches 30 - 50 % following ATD discontinuation . Conflicting results have previously been reported with regard to the usefulness of combining ATD with thyroxine ( l-T4 ) , and thereafter maintaining l-T4 treatment after ATD withdrawal . Also , clinicians are in search of useful parameters to predict the risk of a recurrence of hyperthyroidism after ATD treatment . DESIGN Eighty-two consecutive patients ( 70 women and 12 men ; mean age 36 years ) with a first episode of Graves ' hyperthyroidism were investigated prospect ively ; they were treated with ATD for a total of 15 months , combined with l-T4 ( for at least 12 months ) after they had reached euthyroidism , with the aim of maintaining serum TSH below 2.5 mU/l during the combined therapy . Following ATD discontinuation , the patients were r and omly assigned ( double-blind placebo-controlled trial ) to taking 100 microg/day l-T4 ( vs placebo ) for an additional year . METHODS The following determinations were carried out at initial diagnosis : serum total T4 and tri-iodothyronine ( T3 ) , free T4 and T3 , TSH , TSH-receptor antibodies ( TSHR-Ab ) , thyroid scintigraphy and echography . During ATD treatment , serum free T4 and T3 and TSH concentrations were recorded after 1 ( optional ) , 2 , 4 , 6 , 9 , 12 and 15 months , and echography at the end of ATD treatment . During the r and omized trial , serum free T4 and T3 and TSH concentrations were checked every 3 months ( or until a recurrence ) . TSHR-Ab titers were measured at initial diagnosis , after 6 months with ATD , and at the end of ATD treatment . RESULTS l-T4 administration , both during and after ATD treatment , did not improve the final outcome and recurrence rates were similar in placebo and l-T4-treated patients ( 30 % ) . Two parameters were identified that might be useful to help predict recurrence risks after ATD : ( i ) positive TSHR-Ab ( at the end of ATD treatment ) was significantly associated with a greatly increased recurrence risk ; and ( ii ) despite the relatively small number of patients who were smokers , regular cigarette smoking was shown , for the first time , to be significantly associated with an increased recurrence risk . Also , the deleterious effect of smoking was shown to manifest its impact independently of TSHR-Ab titers at the end of ATD treatment . Thus , compared with the overall 30 % recurrence risk , non-smoking patients with a negative TSHR-Ab ( at the end of ATD ) had a lower ( 18 % ) recurrence risk ; smoking patients with negative TSHR-Ab ( at the end of ATD ) had a 57 % recurrence risk ; non-smoking patients with positive TSHR-Ab ( at the end of ATD ) had a high ( 86 % ) recurrence risk ; the recurrence risk was 100 % in those few patients who both smoked and maintained a positive TSHR-Ab at the end of ATD treatment . CONCLUSIONS The present study confirmed that l-T4 administration during and after ATD withdrawal did not improve remission rate . Two factors , namely positive TSHR-Ab at the end of ATD treatment and regular smoking habits may represent clinical ly useful ( albeit not absolute ) predictors of the risk of recurrence in patients with Graves ' hyperthyroidism treated with ATD . However , due to the relatively small number of smoking patients in the present cohort , this conclusion needs to be confirmed by a larger study CONTEXT Although methimazole ( MMI ) and propylthiouracil ( PTU ) have long been used to treat hyperthyroidism caused by Graves ' disease ( GD ) , there is still no clear conclusion about the choice of drug or appropriate initial doses . OBJECTIVE The aim of the study was to compare the MMI 30 mg/d treatment with the PTU 300 mg/d and MMI 15 mg/d treatment in terms of efficacy and adverse reactions . DESIGN , SETTING , AND PARTICIPANTS Patients newly diagnosed with GD were r and omly assigned to one of the three treatment regimens in a prospect i ve study at four Japanese hospitals . MAIN OUTCOME MEASURES Percentages of patients with normal serum free T(4 ) ( FT4 ) or free T(3 ) ( FT3 ) and frequency of adverse effects were measured at 4 , 8 , and 12 wk . RESULTS MMI 30 mg/d normalized FT4 in more patients than PTU 300 mg/d and MMI 15 mg/d for the whole group ( 240 patients ) at 12 wk ( 96.5 vs. 78.3 % ; P = 0.001 ; and 86.2 % , P = 0.023 , respectively ) . When patients were divided into two groups by initial FT4 , in the group of the patients with severe hyperthyroidism ( FT4 , 7 ng/dl or more , 64 patients ) MMI 30 mg/d normalized FT4 more effectively than PTU 300 mg/d at 8 and 12 wk and MMI 15 mg/d at 8 wk , respectively ( P < 0.05 ) . No remarkable difference between the treatments was observed in patients with initial FT4 less than 7 ng/dl . Adverse effects , especially mild hepatotoxicity , were higher with PTU and significantly lower with MMI 15 mg/d compared with MMI 30 mg/d . CONCLUSIONS MMI 15 mg/d is suitable for mild and moderate GD , whereas MMI 30 mg/d is advisable for severe cases . PTU is not recommended for initial use Objective The study aims to evaluate the efficacy of combination therapy with propylthiouracil ( PTU ) and cholestyramine in the treatment of Graves ’ hyperthyroidism BACKGROUND Antibodies to thyroid-stimulating hormone ( TSH ) receptors that stimulate the thyroid gl and cause hyperthyroidism in patients with Graves ' disease , and their production during antithyroid drug treatment is an important determinant of the course of the disease . One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy . We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole . METHODS AND RESULTS The levels of antibodies to TSH receptors were measured during treatment with methimazole , either alone or in combination with thyroxine , in 109 patients with hyperthyroidism due to Graves ' disease . The patients first received 30 mg of methimazole daily for six months . All were euthyroid after six months , and their mean ( + /- SD ) level of antibodies to TSH receptors decreased from 64 + /- 9 percent to 25 + /- 15 percent ( P less than 0.01 ; normal , 2.9 + /- 1.4 percent ) . Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year . In the thyroxine-treated group , the mean serum thyroxine concentration increased from 108 + /- 16 nmol per liter to 145 + /- 11 nmol per liter ( P less than 0.01 ) , and the level of antibodies to TSH receptors decreased from 28 + /- 10 percent to 10 + /- 3 percent after one month of combination therapy . In the patients who received placebo and methimazole , the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change . Methimazole , but not thyroxine or placebo , was discontinued in each group 1 1/2 years after the beginning of treatment . The level of antibodies to TSH receptors further decreased ( from 6.6 + /- 3.2 percent at the time methimazole was discontinued to 2.1 + /- 1.2 percent one year later ) in the patients who continued to receive thyroxine , but it increased ( from 9.1 + /- 4.8 percent to 17.3 + /- 5.8 percent during the same period ) in the patients who received placebo . One patient in the thyroxine-treated group ( 1.7 percent ) and 17 patients in the placebo group ( 34.7 percent ) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole . CONCLUSIONS The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism Antithyroid drugs are effective in restoring euthyroidism in Graves ' disease , but many patients experience relapse after withdrawal . Prevention of recurrence would therefore be a desirable goal . In a prospect i ve study , patients with successful outcome of 12 to 15 months antithyroid drug therapy were stratified for risk factors and r and omly assigned to receive levothyroxine in a variable thyrotropin (TSH)-suppressive dose for 2 years or no treatment . The levothyroxine group was r and omized to continue or discontinue levothyroxine after 1 year . End points included relapse of overt hyperthyroidism . Of 346 patients with Graves ' disease enrolled 225 were euthyroid 4 weeks after antithyroid drug withdrawal and were r and omly assigned to receive levothyroxine ( 114 patients ) or no treatment ( controls , 111 patients ) . Of those not r and omized , 39 patients showed early relapse within 4 weeks , 61 endogenous TSH suppression , 7 TSH elevation , and 14 had to be excluded . Dropout rate during the study were 13.3 % . Kaplan-Meier analyses showed relapse rates to be similar in the levothyroxine group ( 20 % after 1 year , 32 % after 2 years ) and the r and omized controls ( 18 % , 24 % ) , whereas relapses were significantly more frequent in the follow-up group of patients with endogenously suppressed TSH ( 33 % , 49 % ) . Levothyroxine therapy did not influence TSH-receptor antibody , nor did it reduce goiter size . The best prognostic marker available was basal TSH determined 4 weeks after withdrawal of antithyroid drugs ( posttreatment TSH ) . The study demonstrates that levothyroxine does not prevent relapse of hyperthyroidism after successful restoration of euthyroid function by antithyroid drugs and characterizes posttreatment TSH as a main prognostic marker Forty-nine patients with Graves ' disease were r and omly divided into two groups . One group received propylthiouracil , 150 mg every eight hours , and the other group received propylthiouracil , 450 mg as a single daily dose . All patients ' conditions were evaluated clinical ly anc chemically at two-week intervals . The response to the divided dosage schedule was prompt and predictable , and by ten weeks all but one patient had achieved remission . The group that received the single daily dose regimen responded less favorably , and at ten weeks ten patients had failed to achieve remission ( P less than .001 ) . However , when these patients ' regimens were switched to the every-eight-hour schedule , all but one patient became euthyroid in an additional four weeks Soluble class I major histocompatibility antigens ( sHLA ) , beta 2-microglobulin ( beta 2-M ) , and soluble interleukin-2 receptor ( sIL-2R ) , are secreted by B and T lymphocytes upon activation , and have been used as markers of immune activation in several diseases . Thirty-two Graves ' disease patients were r and omly assigned to three methimazole ( MMI ) regimens of treatment : ( 1 ) low-dose , starting with 45 mg/day , and lowering the dose thereafter to maintain normal serum thyroid hormones ; ( 2 ) MMI 60 mg/day + levothyroxine , and ( 3 ) MMI 30 mg/day + levothyroxine . Serum sHLA , beta 2-M , sIL-2R , TSH receptor antibodies ( TSH-R Ab ) , T3 , and free T4 ( fT4 ) were measured at diagnosis and at weeks 4 , 12 , and 24 ( end of treatment ) . Patients were followed-up after treatment for at least 24 weeks ( 24 to 89 ) . At diagnosis , serum levels of sIL-2R , beta 2-M , sHLA , and TSH-R Ab were elevated . Serum sIL-2R , beta 2-M , sHLA , and TSH-R Ab decreased with treatment . No effect of the varying MMI regimens on these parameters was observed . Soluble IL-2R correlated positively with T3 , fT4 , beta 2-M , sHLA , and TSH-R Ab . Statistically significant , but weak , correlations ( r < 0.35 ) were observed between beta 2-M , sHLA , and TSH-R Ab , between beta 2-M , T3 , and fT4 , and between TSH-R Ab and T3 . Recurrence rates were not associated either with the MMI regimen or any of the parameters studied , with the exception of elevated initial TSH-R Ab levels . Serum sHLA , beta 2-M , and sIL-2R are increased in untreated Graves ' disease , and decrease during treatment . No MMI dose-related differences were observed in these parameters , and in the recurrence rate . Unfortunately , sHLA , beta 2-M , and sIL-2R were not useful predictors of prolonged remission after MMI treatment Although antithyroid drugs ( ATD ) are widely used in the treatment of Graves ' disease , management protocol s , especially treatment duration , remain a subject of debate . The rate of relapse after short‐term regimens of less than 6 months with ATD at decreasing doses is higher than after longer treatments from 12 to 24 months . As no prospect i ve study has provided data on even longer protocol s exceeding 2 years , we conducted a prospect i ve trial to determine potential benefits of a 42‐month treatment compared with an 18‐month treatment Medical treatment of Graves ' disease involves antithyroid drugs with or without the addition of exogenous T4 . There have been conflicting reports as to whether the addition of T4 improves remission rates or delays relapse . To evaluate this issue in a North American population , 199 patients were treated with methimazole until they were euthyroid . They were then r and omized to either methimazole alone in a dose sufficient to normalize TSH ( group 1 ) , or to 30 mg methimazole daily plus sufficient T4 to maintain TSH in the upper normal range ( group 2 ) , or to 30 mg methimazole daily plus sufficient T4 to suppress TSH below 0.6 mIU/L ( group 3 ) . After 18 months , methimazole was stopped , and T4 was continued in groups 2 and 3 . Because not all patients in groups 2 and 3 achieved their target TSH concentration , they were reassigned to group A ( TSH > or = 1.0 ) or group B ( TSH < 1.0 ) , based on the mean TSH achieved during methimazole treatment . One hundred forty-nine patients have been followed for at least 6 months after stopping methimazole ( mean 27 months ) . Fifty-eight percent of patients have relapsed . There were no significant differences in relapse rates after stopping methimazole . Among those patients who did relapse , however , there was a significant difference in the months to relapse after stopping methimazole between groups B and 1 ( group 1 : 3.3 + /- 0.7 , group A : 5.6 + /- 0.8 , group B : 7.4 + /- 1.7 ; P = 0.01 for the comparison between groups B and 1 ) . We conclude that the addition of T4 to methimazole does not improve long-term remission rates in Graves ' disease We present the conclusions of two prospect i ve studies of patients examined at their first manifestation of Graves ' disease and treated with antithyroid drugs ( ATD ) . The purpose of the first study was to investigate the effects of long-term treatment : the patients were given carbimazole in degressive doses without hormone replacement for 18 months , the followed up for 2 to 6 years after drug withdrawal . The second study was design ed to determine the effect of treatment duration on the prognosis : the patients were given an ATD according to the same protocol for a duration r and omly set at either 6 or 18 months , then seen again 2 years after ATD withdrawal . The results showed that after 18 months of treatment at least 50 percent of the patients could be expected to remain in remission for 6 years . Remissions were less frequent when treatment was shorter ( 41.7 percent after the 6 month treatment versus 61.8 percent after the 18 month treatment , with a 2 years ' follow-up ; P less than 0.05 ) . The relapses that occurred came early : 70 percent of them took place within the first post-treatment month . This article also provides evidence of high T3 and /or T4 levels without signs of thyrotoxicosis during the post-treatment clinical course ; these exclusively biochemical relapses spontaneously disappeared and may have been expressing epidoses of active thyroiditis . ( ABSTRACT TRUNCATED AT 250 WORDS A prospect i ve r and omized study was performed in patients with hyperthyroid Graves ' disease ( GD ) in order to compare long ( 18 months ) and short term ( 6 months ) antithyroid drug treatment on the remission rate . A therapeutic protocol was offered to all GD patients who had not been treated for this disease previously . All patients studied who followed the protocol were rechecked 2 yr after treatment was withdrawn , or earlier in the case of relapse . Of the patients having undergone long term treatment , 61.8 % still were in remission 2 yr after treatment withdrawal , whereas only 41.7 % of the patients treated for 6 months were in remission ( P less than 0.05 ) . Such findings clearly establish that treatment duration has a direct beneficial incidence on the remission rate . These results were confirmed by the fact that treatment for 18 months result ed in remission in 7 of 15 patients who had previously relapsed after a 6-month course of therapy . This improvement in relation to treatment duration might be due to the immunosuppressive action of carbimazole . No significant difference was observed between relapse and remission groups , regardless of treatment duration , for HLA ABDr , serum T3 and T4 , and T3/T4 ratio determined before treatment . Only the thyroid-stimulating antibody levels determined at the time of diagnosis and at the end of treatment were higher in the relapse group , a difference that was relevant only globally , due to value scattering . Furthermore , thyroid-stimulating antibody levels at the end of treatment may indicate remission or , conversely , continuance of the pathological process . ( ABSTRACT TRUNCATED AT 250 WORDS In a prospect i ve study to determine which factors would predict remission or relapse , 65 patients with hyperthyroid Graves ' disease were treated for six months with a blocking replacement regimen of carbimazole , 40 mg daily , and triiodothyronine ( T3 ) . They were followed for one year after stopping treatment , by which time 32 ( 49 per cent ) had relapsed . Although the treatment protocol , relapse rate and frequency of the HLA-DR3 antigen in this population were similar to those of a regionally separate Graves ' population investigated previously , the predictive value of HLA-DR3 status together with thyroid stimulating antibody ( TSAB ) levels was strikingly different . In the present study there was no significantly abnormal distribution of any HLA antigen in the relapse group compared with those patients who achieved remission . Thyroid stimulating antibodies were detected in 62 patients ( 95 per cent ) and fell significantly ( p less than 0.05 ) after carbimazole treatment , irrespective of DR3 status or outcome ; TSAB levels only became undetectable in nine patients ( 28 per cent ) who subsequently relapsed and in nine patients ( 30 per cent ) who maintained remission . T3-suppressed 20 min 123I uptake fell equally after treatment in the relapse and remission groups but continued to fall thereafter in the group which maintained remission . In these patients , 123I uptake was significantly lower at the end of the study period than at the end of treatment ( p less than 0.05 ) . Serum free T4 levels were higher before treatment in the patients who later relapsed than in those whose disease remitted ( p less than 0.02 ) . This proved the only significant marker associated with outcome but was of little predictive value in any patient . This study highlights the problem in predicting the outcome of antithyroid drug treatment , since even within the same country under similar conditions , divergent results have been obtained . It appears that the loci controlling the immune response in Graves ' disease are likely to include genes lying outside the HLA-DR region . The results also suggest that the immunological effects of antithyroid drugs are maintained after stopping treatment in those patients whose disease remits Sixty patients with Graves ' disease ( GD ) hyperthyroidism were distributed in two r and omized groups . Patients in group A ( n = 30 ) received carbimazole by a titration regimen , and patients in group B ( n = 30 ) were treated with higher doses of carbimazole plus T4 . Clinical and analytical evaluations were done at baseline , during treatment ( 18.4 + /- 2.6 months ) , and after , until the relapse of hyperthyroidism , or for 4.98 + /- 1.6 yr in patients who did not relapse . There were no differences in clinical parameters , thyroid hormones , or TSH binding inhibitory immunoglobulins ( TBII ) levels between the two groups , either at baseline or at the end of treatment . Serum TSH persisted undetectable in 16 out of 60 patients ( group A : 9 ; group B : 7 ) , after treatment . Relapse occurred in 38 patients ( 63.3 % ) , ( group A : 18 ( 60 % ) vs. group B : 20 ( 66.7 % ) ) . Patients who relapsed had bigger goiters at baseline ( P = 0.02 ) and at the end of treatment ( P = 0.03 ) . Eighty-seven percent ( 14/16 ) of patients with undetectable TSH after therapy relapsed , vs. 54.5 % ( 24/44 ) of those with normal TSH ( P = 0.01 ) . Undetectable TSH at the end of treatment was the only independent variable in the logistic analysis to predict relapse . Treatment modality did not influence the relapse rate . This study has found that , in Spanish patients , the use of high doses of carbimazole with T4 offers no advantages in the treatment of GD hyperthyroidism Antithyroid drugs are commonly used as first-line treatment for Graves ' disease , but the optimum regimen for inducing remission remains unclear . We gave the block-replace regimen of carbimazole plus thyroxine to 100 patients for 6 or 12 months , to determine whether prolonged treatment is associated with fewer relapses . The remission rate one year after cessation of treatment was 59 % with the 6 month course and 65 % with 12 months ; this was not significantly different . We also analysed HLA markers identified by restriction fragment length polymorphisms and could not confirm the recently reported associations of outcome with HLA-DR4 or with an HLA-DQA2 allele . These results show that six months treatment with a block-replace regimen of antithyroid drugs is probably sufficient , in the UK , to achieve maximum remission of Graves ' disease and that there are no HLA markers which clearly predict outcome We evaluated the efficacy of different doses of methimazole ( MMI ) as the initial therapy for Graves ’ disease . Fourteen patients were treated with 15 mg/die of the drug ( group A ) and 14 with 30 mg/die ( group B ) . Blood sample s for T3 , T4 , FT3 and FT4 were obtained before beginning therapy , every 48 h during the first 12 days and on the 45th day of treatment . All these hormonal parameters fell significantly from the 2nd day of therapy in both groups . All the patients , except for one in group B , had normal or subnormal levels of thyroidal hormones on the 45th day of treatment . The comparison between the two groups of regression coefficients over the first 12 days showed no significant differences . The absolute decrease of each examined parameter on day 12 was positively correlated with the relevant pretreatment value . These results demonstrate that doses of MMI ( 15 mg/die ) much lower than those commonly recommended are able to rapidly control thyroidal overproduction as effectively as 30 mg/die Some studies have suggested that increasing the daily dose of anti-thyroid drugs might improve long-term remission rates of Graves ' disease . Therefore , this question was addressed in a prospect i ve multicenter trial involving 18 thyroid clinics in Europe , mostly in iodine-deficient or moderately iodine-sufficient regions . Five hundred and nine patients with Graves ' hyperthyroidism were enrolled in a prospect i ve r and omized trial comparing the remission rates after treatment with methimazole ( MMI ) at two fixed dosages ( 10 vs. 40 mg ) with levothyroxine supplementation . The treatment and follow-up periods lasted 12 months each . Sixty and seven-tenths percent of the recruited patients ( total , 309 ; 153 in the 10 mg , 156 in the 40 mg group ) were finally evaluated , and comparison of the two groups showed that they were well matched with respect to a wide range of variables , including parameters of thyroid function . With 10 mg MMI daily , 68.4 % of the patients were euthyroid after 3 weeks , and 84.9 % after 6 weeks , compared to 83.1 % and 91.6 % , respectively , with the use of 40 mg MMI daily . TSH receptor antibodies decreased similarly in the two groups , 25 % of patients in the 10 mg group , and 30 % in the 40 mg group still being TSH receptor antibodies positive after 12 months . One hundred and ninety six ( 63.4 % ) of the 309 patients achieved remission of Graves ' disease . The two MMI doses were equally effective ; 35.9 % compared to 37.2 % of patients treated with 10 and 40 mg MMI , respectively , had relapses . There was no difference in the length of the time interval between stopping treatment and recurrence between the two groups . However , the rate of adverse drug reactions increased from 39/251 ( 15.5 % ) in the 10 mg group to 67/258 ( 26.0 % ) in the 40 mg group ( P < 0.01 ) . Under conditions of iodine deficiency or borderline sufficient iodine supply , 40 mg MMI daily will render more patients with Graves ' disease euthyroid within the first 6 weeks of treatment than 10 mg daily , but at the expense of an increased rate of adverse reactions . However , patients treated with 40 mg MMI daily for 1 yr have no higher chance of remission than patients treated with 10 mg . It does not appear justified at present to recommend MMI doses higher than required for the control of hyperthyroidism ( with the goal of immunosuppression ) INTRODUCTION Hyperthyroid Graves ' disease ( GD ) is a B-cell-mediated condition caused by TSH receptor antibodies ( TRAb ) , which decline when GD remits . Anti-CD20 monoclonal antibody rituximab ( RTX ) induces transient B-cell depletion that may potentially modify the active inflammatory phase of thyroid-associated ophthalmopathy ( TAO ) . METHODS Nine patients with GD , ( seven with active TAO , two with mild lid signs ) were studied . The trial was only approved as an open pilot study ; thus we compared the effect of RTX therapy to that of i.v . glucocorticoids ( IVGC ) in 20 consecutive patients . Patients were treated with RTX ( 1000 mg i.v . twice at 2-week interval ) or with IVGC ( 500 mg i.v . for 16 weeks ) . TAO was assessed by the clinical activity score ( CAS ) and severity was classified using NOSPECS ( No signs or symptoms ; Only signs ( lid ) ; Soft tissue involvement ; Proptosis , Extraocular muscle involvement ; Corneal involvement ; Sight loss ) . Thyroid function and lymphocyte count were measured by st and ardized methods . RESULTS All patients attained peripheral B-cell depletion with the first RTX infusion . Minor side effects were reported in three patients . Thyroid function was not affected by RTX therapy and hyperthyroid patients required therapy with methimazole . After RTX , the changes in the levels of thyroglobulin antibodies , thyroperoxidase antibodies and TRAb were neither significant nor correlated with CD20 + depletion ( P = NS ) . CAS values before RTX were 4.7 + /- 0.5 and decreased to 1.8 + /- 0.8 at the end of follow-up ( P < 0.0001 ) and more significantly compared with IVGC ( P < 0.05 ) . Proptosis decreased significantly after RTX both in patients with active TAO ( ANOVA ; P < 0.0001 ) and those with lid signs ( ANOVA ; P < 0.003 ) . The degree of inflammation ( class 2 ) decreased significantly in response to RTX ( ANOVA ; P < 0.001 ) . Relapse of active TAO was not observed in patients treated with RTX , but occurred in 10 % of those treated with IVGC , who also experienced adverse effects more frequently ( 45 vs 33 % of patients ) . CONCLUSIONS RTX positively affects the clinical course of TAO , independently of either thyroid function or circulating antithyroid antibodies , including TRAb . If our findings are confirmed in large controlled studies , RTX may represent a useful therapeutic tool in patients with active TAO OBJECTIVES To compare the relapse rates in Graves ' disease the first 2 years after methimazole 60 mg day-1 combined with thyroxine versus a titration regimen with methimazole alone , and to look for possible prognostic factors . DESIGN A r and omized , open , prospect i ve study . Methimazole was given for 6 months in both groups , and thyroid status evaluated every 3rd month during the first year , and every 6th month during the second year . SETTING The study was performed at our outpatient clinic with patients referred from primary care . SUBJECTS Fifty-six patients were included . One became pregnant and one dropped out during the treatment period . Furthermore , nine patients in the high-dose and four in the low-dose group stopped the treatment because of side-effects . Thus , 19 patients in the high- and 22 in the low-dose group completed 6 months with methimazole . RESULTS In those tolerating the treatment , the relapse rates in the high- and low-dose groups were 26.3 vs. 59.1 % ( P < 0.05 ) , 42.1 vs. 77.3 % ( P < 0.02 ) ; and 57.9 vs. 77.3 % ( NS ) after 3 , 12 and 24 months , respectively . The corresponding relapse rates calculated on an ' intention to treat ' basis were : 51.7 vs. 66.7 % ; 62.1 vs. 81.5 % : 72.4 vs. 81.5 % ( NS ) . The thyroid volume was significantly ( P < 0.05 ) larger in those that relapsed ( 17.8 + /- 2.9 vs. 11.6 + /- 1.2 mL ; mean + /- SEM ) . CONCLUSIONS In those tolerating the treatment , methimazole significantly reduced the relapse rate the 1st year when given in a high dose . However , the relapse rates in both groups , and the number of side-effects in the high-dose group , were unacceptably high Since theraphy of Graves ' disease is not directed towards the cause of the disease , medical theraphy is still the first choice and symptomatically effective in treating hyperthyroidism . Antithyroid drugs are effective in restoring euthyroidism in > 90 % of the patients durning 4 - 6 weeks , but 30 - 50 % of the patients experience relapse after withdrawal . Previous prospect i ve r and omized studies evaluated prognostic parameters and the use of levothyroxine for prevention of relapse of hyperthyroidism . Recent studies have addressed the period after withdrawal amd focused on the natural course of disease . The results of a recent prospect i ve r and omized and controlled multicenter study were as follows : supplementation of levothroxine does not prevent relapse of hyperthyroidism . Basal TSH ( 4 weeks after withdrawal of antithyroid drugs ) is the best prognostic marker . Smoking and positive TSH-receptor-antibodies at the end of antithyroid theraphy are other risk factors TSH has been incriminated in Graves ’ disease for increasing the production of antibodies against TSH receptor ( TRAb ) . It has been , therefore , suggested that T4 administration after successful antithyroid drug ( ATD ) treatment may indirectly decrease the production of TRAb and , therefore , the frequency of recurrence of hyperthyroidism . To study the role of T4 and T3 on the recurrence rate of Graves ’ disease 108 patients with Graves ’ disease ( 22 males , age : 49.8±14.3 yr , mean±SD , and 86 females , age : 41.7±12 yr ) were followed-up for 24 months after successful treatment with ATD ( carbimazole ) . During the follow-up period , patients daily received either 100 μg T4 or 25 μg T3 or placebo after r and om and double-blinded assignment into three groups . They were evaluated trimonthly up to 12 months and at 24 months . Plasma TRAb levels were measured at the beginning and at 12 months . At 12 months of the follow-up period , 14 out of 33 ( 42.4 % ) , 6 out of 38 ( 15.8 % ) , and 9 out of 37 ( 24.3 % ) patients receiving T4 , T3 and placebo , respectively , recurred . Recurrence rate of T4-treated patients was statistically higher than that of the T3-treated patients or controls ( p<0.05 ) . At the beginning of the follow-up period patients who were going to recur had significantly higher TRAb levels and goiter weight than patients who were not ( p<0.05 ) . At 24 months of the follow-up period , from the patients who did not drop out of the study , none out of 11 ( 0 % ) , 2 out of 19 ( 10.5 % ) and 1 out of 12 ( 8.3 % ) receiving T4 , T3 and placebo , respectively , recurred . We conclude that T4 administration after successful ATD treatment of Graves ’ disease is associated with increased recurrence of hyperthyroidism as compared to the T3 or placebo administration . High TRAb levels and goiter weight at the end of ATD treatment may hint at recurrence OBJECTIVE To investigate the effect of different antithyroid drug ( ATD ) regimens on relapse rates of Graves ' disease , and to look for predictors of relapse . DESIGN AND METHODS In a prospect i ve two-way factorial r and omized clinical trial , 218 patients with Graves ' disease were assigned to ATD combined with l-thyroxine ( l-T(4 ) ) or ATD alone for 12 Months . After discontinuation of antithyroid therapy , each group was stratified to either 12 Months further treatment with l-T(4 ) or no treatment . Clinical and biochemical assessment s were carried out before treatment , after 3 and 6 weeks , and every third Month for 12 Months . If the patients lacked symptoms of relapse , laboratory tests were performed every third Month for the second Year , and thereafter annually . RESULTS The proportion of all patients with relapse was 47.7 % 2 Years after withdrawal of ATD . There was no difference in relapse rates between the treatment groups ( P=0.217 , log -- rank test ) . Smokers had a higher relapse rate than non-smokers ( 58.4 % vs 38.8 % , P=0.009 ) . Patients who were thyrotropin-receptor antibody ( TRAb ) positive after 12 Months of antithyroid therapy had a higher relapse rate than those who were negative ( 72.5 % vs 36.8 % , P<0.0001 ) . Similarly , relapse was more frequent ( 55.5 % ) in patients having large goiter compared with subjects with small goiter ( 36.3 % , P=0.0007 ) . CONCLUSIONS Relapse rates of Graves ' disease were independent of ATD regimen whether followed by l-T(4 ) therapy or not . Smoking , large goiter and presence of TRAb at the end of ATD therapy were strong predictors of relapse Previous studies of the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a favourable result with methimazole ( MMI ) . However , the efficacy of a single daily dose of propylthiouracil ( PTU ) was inconsistent . The present prospect i ve r and omized study was conducted to compare the efficacy of a single daily dose of MMI and PTU in the induction of euthyroidism in patients with Graves ' disease We studied the influence of TSH suppressive therapy combined with carbimazole ( CBZ ) on treatment outcome in Graves ' disease OBJECTIVES To obtain a simple st and ard regimen , suitable for general practice , and based upon the addition of antithyroid drug plus thyroxine for attaining euthyroidism in patients with Graves ' disease . DESIGN Prospect i ve , r and omized trial of patients with Graves ' disease followed for 3 months after the initiation of therapy with an antithyroid drug and combined with the later addition of triiodothyronine to keep the patient euthyroid . The patients were r and omized , according to birth date , between methimazole and propylthiouracil . Three dose schemes were tested for each antithyroid drug . SETTING The study was performed at the thyroid outpatient units of two general hospitals , with the patients having been referred from primary care . SUBJECTS Ninety-four patients with Graves ' disease who were suitable for treatment with antithyroid drugs . INTERVENTIONS The patients were allocated into six groups . Three groups received methimazole ( 10 mg every 6th , 8th or 12th h ) and three received propylthiouracil ( 100 mg every 6th , 8th or 12th h ) . Twenty micrograms of triiodothyronine was added when the patients were euthyroid to avoid hypothyroidism . MAIN OUTCOME MEASURES The lowest serum free thyroxine level within 3 months of the initiation of the antithyroid treatment . RESULTS Fourteen per cent of the patients on methimazole 10 mg every 12th h and 29 % on propylthiouracil 100 mg every 12th h did not achieve euthyroidism within the 3-month observation period . All but one patient on methimazole 10 mg every 8th h or propylthiouracil 100 mg every 8th h reduced the free serum thyroxine levels to the normal or hypothyroid range within the observation period . All of the patients on methimazole 10 mg every 6th h and 56 % on propylthiouracil 100 mg every 6th h reduced the serum T4 values into the hypothyroid range within the period . CONCLUSION A st and ard regimen , based upon the addition of methimazole 10 mg every 8th or 6th h or propylthiouracil 100 mg every 8th or 6th h and followed by the addition of thyroxine or triiodothyronine when euthyroid to avoid hypothyroidism , seems to be suitable for attaining euthyroidism within 3 months in patients with Graves ' disease . A dose scheme based on methimazole 10 mg every 12th h or propylthiouracil 100 mg every 12th h were found to be unsuitable due to an unacceptably high incidence of failure to attain euthyroidism or hypothyroidism within 3 months objective The present study was to compare the efficacy of a single daily dose of methimazole ( MMI ) and propylthiouracil ( PTU ) in the treatment of Graves ’ hyperthyroidism Objective : To investigate the significance of treatment with antithyroid drugs longer than 12 months on lasting remission in Graves ’ hyperthyroid patients , and to study clinical and laboratory parameters of prognostic value . Patients : Fifty-two untreated Graves ’ hyperthyroid patients were assigned at r and om to two therapeutic groups . They were treated with Carbimazole during 12 and 24 months in Group I ( n= 28 ) and Group II ( n= 24 ) , respectively . Measurements : Serum levels of FT4 , T3 , sTSH and TSH receptor antibody ( TRAb ) were measured before starting treatment and at regular intervals during treatment and follow-up after drug withdrawal . We compared the relapse rate in both groups of patients , at short ( 2-yr ) and long-term ( 5-yr ) periods after drug withdrawal . Also , we compared clinical and biochemical parameters between patients who stayed in remission and who had relapse . Results : At the end of the short-term period , relapse had occurred in 13 ( 46.4 % ) Group I patients and in 13 ( 54.1 % ) Group II patients , p=0.36 . At the end of the long-term period , relapse had occurred in 24 ( 85.7 % ) Group I and 20 ( 83.3 % ) Group II patients , p=0.78 . No difference could be observed between patients who had stayed in remission and who had suffered relapse , within the 5-yr follow-up period regarding to goiter size , frequency of ophthalmopathy , TSH and TRAb levels . Conclusions : The high relapse rate observed could be due to high iodine intake in our country . In this study and in a review of the available data , we have been unable to find any rational basis for courses of antithyroid drugs longer than twelve months for the treatment of Graves ’ hyperthyroidism . Nor is a reliable prognosis for an individual patient possible by TRAb determination at any given time during therapy , owing to the low sensitivity and specificity of this variable Little is known about the immunosuppressive effect of glucocorticoids on TSH receptor antibodies . We observed the long-term prognosis and serum TSH binding inhibitor immunoglobulin ( TBII ) levels in patients with Graves ' ophthalmopathy who had received intravenous methylprednisolone pulse therapy ( pulse therapy ) followed by oral prednisolone administration in order to ascertain how long the immunosuppressive effect of glucocorticoids continued . This is the first report on the effect of pulse therapy on Graves ' disease outcome . We observed 67 patients who were treated by antithyroid drugs ( ATD ) alone for 2 years after pulse therapy . TBII was evaluated before and 3 , 6 , 12 , 18 , and 24 months after pulse therapy . The mean TBII decreased significantly 3 months after pulse therapy ( p<0.001 ) , and was maintained until 24 months . There were 24 patients whose TBII was positive ( > 15 % ) at 24 months , in whom the mean TBII decreased significantly 3 to 6 months after pulse therapy ( p<0.001 ) , but increased again at 12 to 24 months ( p<0.05 ) . Thus , the immunosuppressive effect of glucocorticoids may be lost at 12 months after pulse therapy in these patients . The remission rate in the pulse therapy group was 40.98 % , and that of the control patient group was 48.57 % . There was no significant difference between the two . These results suggest that the immunosuppressive effect of pulse therapy was temporary , and that pulse therapy did not increase remission rate of Graves ' disease OBJECTIVE Conventional therapies for Graves ' disease , consisting of medical therapy or radioiodine are unsatisfactory , because of limited efficacy and adverse events . Interventions aim ed at the underlying autoimmune pathogenesis of Graves ' disease may be worthwhile to explore . We therefore performed a prospect i ve , 26-week phase II study with open-ended observational extension to assess the efficacy of rituximab in patients with recurrent Graves ' disease . DESIGN We performed a prospect i ve , 26-week phase II study with open-ended observations . METHODS Thirteen patients with relapsing Graves ' disease ( 9 females and 4 males , age 39.5+/-9.5 years ) received 2 dosages of rituximab 1000 mg i.v . with a 2-week interval . Before administration and on several periods after the administration of TSH , free thyroxine ( FT(4 ) ) , thyrotropin binding inhibitory immunoglobulins ( TBII ) and the proportion of CD19 and MS4A1 positive peripheral blood mononuclear cells were measured . RESULTS The proportion of MS4A1 positive lymphocytes decreased in all patients from 5.8 % at baseline to 1.4 % at 26 weeks ( P=0.007 ) . Four patients with high initial FT(4 ) levels did not respond to treatment . All remaining patients had a decrease in FT(4 ) levels at 26 weeks ( P=0.001 ) and an increase in TSH levels ( P=0.011 ) . TBII decreased in all remaining patients ( P=0.003 ) . At a follow-up time of 14 - 27 months , nine of these patients were still euthyroid with normal FT(4 ) ( P<0.001 ) and TSH levels ( P=0.008 ) . CONCLUSIONS The present study results suggest a beneficial role of rituximab in mild relapsing Graves ' disease . A subsequent r and omized controlled trial with rituximab is recommended CONTEXT Graves ' disease ( GD ) is a common TSH receptor autoantibody (TRAb)-mediated disorder . Because B lymphocytes are important self-antigen presenting cells and precursors for antibody-secreting plasma cells , temporary B-lymphocyte depletion with the monoclonal antibody rituximab ( RTX ) might be of benefit in GD . OBJECTIVE / DESIGN The objective of this prospect i ve , controlled , nonr and omized study was to investigate the effect of RTX in GD . SETTING / PATIENTS We studied 20 out patients referred to a university clinic with newly diagnosed ( four with relapse ) untreated GD . Ten received RTX ( + RTX ) , whereas 10 did not ( -RTX ) . INTERVENTION The patients received methimazole ( MMI ) for a median of 102 d ( + RTX ) and 110 d ( -RTX ) before the study . Patients in the + RTX group received 375 mg RTX/m(2 ) iv on d 1 , 8 , 15 , and 22 , and all patients were withdrawn from methimazole ( MMI ) at d 22 . MAIN OUTCOME MEASURES We measured time to relapse of hyperthyroidism and changes in autoantibody levels . RESULTS Four patients in the + RTX group remained in remission with a median follow-up of 705 d ( range , 435 - 904 d ) , whereas all the patients in the -RTX group had relapsed by d 393 ( P < 0.05 ) . All of the patients in remission had initial TRAb levels below 5 IU/liter ( normal , < 0.7 IU/liter ) . However , none of the five patients in the -RTX group with correspondingly low TRAb levels were in remission ( P < 0.01 ) . RTX treatment did not affect autoantibody levels to a greater extent than did MMI monotherapy . Two patients received glucocorticoids for joint pain after RTX therapy . CONCLUSIONS RTX treatment may induce sustained remission in patients with GD with low TRAb levels . However , RTX did not affect autoantibody levels and seems ineffective in patients with high TRAb levels . At present , high cost , low efficacy , and potential side effects do not support use in uncomplicated GD Of 24 patients with newly diagnosed thyrotoxicosis , 13 were r and omly selected for treatment with methimazole 40 mg per day , and 11 for treatment with lithium carbonate in such doses that the serum lithium lay between 0 - 5 and 1 - 3 meq . per litre . The lithium treatment brought about a fall in serum-thyroxine iodine ( T4I ) of 27.0 % , and in the free-thyroxine index ( F.T.I. ) of 38.1 % after 10 days . A comparison of the two patient groups with regard to the fall in F.T.I. after 3 and 10 days showed no statistically significant difference ; similarly the calculated confidence limits appeared to exclude any difference of clinical importance . 8 of the 11 patients subjected to lithium treatment had side-effects , so that the general condition , which was already affected by the hyperthyroidism , was worsened . It is concluded that lithium can not be considered superior to thiocarbamides for the rapid control of thyrotoxicosis Based on findings that thyroxine may have a beneficial effect on the recurrence of Graves ' hyperthyroidism , we prospect ively studied the effects of a TSH suppressive treatment with thyroxine on the course of Graves ' disease in fifty patients with recent onset of hyperthyroidism . After the normalization of serum tri-iodothyronine ( T3 ) and thyroxine ( T4 ) concentrations , one group of patients was r and omly assigned to a combined treatment with carbimazole and a TSH suppressive dose of T4 for 12 months , followed by another 12 months of TSH suppressive therapy alone . The other group of patients also received carbimazole for one year , but T4 was only added as indicated to normalize elevated TSH serum concentrations , and patients received no therapy during the second year . By the end of the second year , a relapse of hyperthyroidism had occurred in 43 % of the patients with and in 45 % of the patients without suppressive T4 treatment . In those patients without a relapse of hyperthyroidism , initial thyroid size significantly ( P = 0.01 ) decreased with time in both treatment groups . However , patients on suppressive T4 treatment tended to have a greater reduction in thyroid volume than patients with normal TSH serum concentrations ( P = 0.05 ) . In conclusion , we were unable to detect a preventive effect of exogenous TSH suppression on the recurrence of hyperthyroidism . However , our data suggest that TSH suppressive treatment may have a beneficial effect on thyroid enlargement in Graves ' disease In a prospect i ve , r and omized study of 135 newly diagnosed patients with hyperthyroidism due to Graves ' disease we compared the effect on remission rates of additional triiodothyronine ( T3 ) with conventional antithyroid drug therapy . To this end 114 patients were followed for at least 12 months ( 15.7+/-4.9 , mean+/-s.d . ) after the discontinuation of any therapy . After return of thyroid function to normal ( 8.5+/-7.4 weeks , mean+/-s.d . ) patients were maintained on antithyroid medication for 9.0+/-2.5 months . They were then r and omly assigned to one of three groups : group 1 ( n=44 ) stopped methimazole , groups 2 ( n=39 ) and 3 ( n=31 ) continued with exogenous T3 ( not exceeding 75 microgram/day in any patient ) for a further 6 months either with ( group 2 ) or without ( group 3 ) a fixed dose of 10 mg methimazole daily . The T3 dose was kept variable to keep TSH suppressed ( < 0 . 1mU/l ) , which could be achieved in 82 % of patients on 100 % of their monthly visits . No serious side-effect requiring the discontinuation of the study occurred in any patient . Total T3 , TSH-receptor antibodies and some previously suggested potential predictors of relapse including thyroid size by ultrasound , 24h urinary iodine excretion , history of cigarette smoking and ophthalmopathy were determined at the outset of the study and subsequently every 6 months ( and total T3 every 4 weeks ) . No significant difference ( P>0.05 , Chi square ) was seen in relapse of hyperthyroidism after a mean follow-up of 16 months ( range : 12 - 31 months ; groups 1:52 % , 2:44 % and 3:42 % ) in an area of low-to-moderate iodine intake ( prevalence of 24h urinary iodine excretion < 100 microgram/24h : 17 and 25 % at two different measurements respectively ) . Concomitantly , no predictor of recurrence of disease could be identified , irrespective of treatment modality The optimal treatment regimen with thionamide drugs remains a matter for debate . We have investigated whether high doses of carbimazole , when compared with low doses , reduce relapse rates of Graves ' disease Increased levels of antibodies to TSH receptors are thought to be a major cause of active Graves ' disease or recurrence following therapy . It was recently reported that T4 administration during antithyroid drug treatment for Graves ' disease result ed in a significant decrease of TSH receptor antibodies compared to drug therapy alone . It is known that these antibodies may remain elevated long after patients become euthyroid , so a large number of patients whose antibodies remained significantly elevated after 1 year of methimazole therapy were evaluated in the study . A total of 330 Graves ' disease patients were treated with methimazole for 1 year . TSH receptor antibody titers remained persistently elevated in 195 patients . Thirty-five r and omly selected patients were continued on maintenance doses of methimazole for a second year , and 160 patients were treated with a combination of methimazole and thyroxine for a second year . T4 doses needed ranged from 75 - 100 micrograms/day to maintain serum-free T4 and free T3 within the normal range . After 6 months of combined therapy , 35 patients were found to have suppressed serum TSH levels . The patients were divided after 18 months into three groups : A , B , and C. Group C , consisting of 35 r and omly selected patients ( 8 males and 27 females ) whose ages ranged from 12 - 62 years and who had been maintained on methimazole alone , served as controls . Group B , whose serum TSH levels were suppressed after 6 months of combined therapy , consisted of 9 males and 26 females whose ages were 15 - 66 years . Group A , 35 r and omly selected patients with normal serum TSH levels after methimazole and thyroxine therapy for 6 months , consisted of 8 males and 27 females whose ages were 10 - 63 years . TSH receptor antibody titers gradually decreased in all three groups with drug therapy , and there was no significant difference in the titers at corresponding times , i.e. 0 , 1.0 , 1.5 , and 2.0 years . After treatment for 2.0 years , all patients of the three groups were followed for a further 12 months . Rates of recurrence among the above three groups were not significantly different during the observation period . In the present study , T4 administration in combination with antithyroidal drugs had no effect on levels of antibodies to TSH receptors and no effect on rates of recurrence . The reason for the discrepant results in the present study from previous reports is not known The enterohepatic circulation of thyroxine ( T4 ) and triiodothyronine ( T3 ) is higher in thyrotoxicosis . Bile-salt sequestrants bind iodothyronines and thereby increase their fecal excretion . We , therefore , evaluated the effect of colestipol-hydrochloride administration on clinical and biochemical indices of patients with hyperthyroidism . In a prospect i ve , controlled trial , ninety-two adult volunteers with Graves ’ disease , toxic autonomous nodule or toxic multinodular goiter were r and omly assigned into the following treatment protocol s : Group 1 , 30 mg of methimazole ( MMI ) and 20 g of colestipol-hydrochloride ( COL ) daily ; Group 2 , 30 mg of MMI daily ; and Group 3 , 15 mg of MMI 20 g of COL daily . The patients were further classified into Group A , severe hyperthyroidism ( baseline levels of total T3 ( TT3 ) ≥5nmol/l ) and Group B , mild to moderate thyrotoxicosis ( baseline levels of TT3<5 nmol/l ) . Crook ’s clinical index , serum free T4 ( FT4 ) , TT3 and thyroid stimulating hormone ( TSH ) levels were determined before ( W0 ) , following one week ( W1 ) and two weeks ( W2 ) of treatment . Serum TT3 level decreased ( mean±SE ) at W1 by 40.8±2.6 % of W0 in Group 1 and by 29.2±2.4 % in Group 2 ( p<0.001 ) , and down further to 47.8±3.0 % at W2 in Group 1 , and 40.6±2.8 % in Group 2 ( p=0.01 ) . Serum FT4 level decreased ( mean±SE ) from W0 to W1 by 31.7±2.7 % in Group 1 and by 16.2±3.1 % in Group 2 ( p=0.005 ) , and down to 49.1±2.8 % of W0 at W2 in Group 1 and to 38.7±3.5 % in Group 2 ( p=0.07 ) . In sub groups B COL was not effective in reducing thyroid hormone levels nor in ameliorating the clinical status of the patients . However , in Group A3 COL lowered FT4 ( p=0.001 ) and TT3 ( p=0.05 ) levels as compared to group A2 . At W2 the clinical hyperthyroidism score improved faster in Group A1 ( p<0.001 ) and Group A3 ( p=0.012 ) as compared to the control Group A2 . In conclusion , COL is an effective and well tolerated adjunctive agent in the treatment of hyperthyroidism . Its main effect is in severe cases of thyrotoxicosis , and in the first phase of treatment . As adjunctive COL treatment in hyperthyroidism allows reducing MMI dosage it may decrease the rate of dose dependent MMI side effects A prospect i ve r and omized trial with the conventional divided doses ( 10 mg 3 times daily , N = 29 ) and a small single daily dose ( 15 mg once daily , N = 25 ) of methimazole for the treatment of Graves ' hyperthyroidism was performed . Within 8 weeks , almost 80 % of the patients in both groups became euthyroid . The mean time required to achieve the euthyroid state was 6.0 + /- 2.8 and 6.0 + /- 3.8 weeks , respectively . TSH binding inhibitor immunoglobulin was found in about 90 % of the patients in both groups before methimazole treatment . However , a gradual fall of its levels was observed in nearly all patients after treatment . There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy . We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves ' hyperthyroidism in most patients , and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen ( 10 mg 3 times daily ) The optimal antithyroid drug regimen for Graves ' disease remains a matter of controversy . The European Multicentre Trial Group has investigated the effects of methimazole drug dose on the long‐term outcome of Graves ' disease A comparative study of high-dose ( HD , carbimazole 60 mg plus thyroxine 100 - 150 micrograms daily ) and titration-dose ( TD ) regimens of carbimazole was carried out in 70 patients with Graves ' disease , the patients being assigned r and omly to one or other regimen . The treatment was given for 1 year and follow-up was for 2 years after stopping treatment . In both groups , recurrence of hyperthyroidism occurred , most commonly during the first 6 months ( 35 % of HD and 44 % of TD ) . By 2 years after stopping treatment , recurrence had occurred in 50 % of the HD and 66 % of the TD group . The differences were not significant . Thyroid antibodies , serum thyroglobulin and pertechnetate uptake fell similarly in both groups during treatment . Cigarette smoking was similar in both the groups and did not influence the frequency of relapse . In both HD and TD groups , when relapsing patients were examined according to whether they relapsed early ( within 6 months or less ) or late it was found that those who relapsed late were , in respect of goitre size , pertechnetate uptake and presence of detectable plasma TSH , similar to the patients who did not relapse at all . In conclusion , the changes in the measured variables and the progress of the patients was similar whether treated by the HD or TD regimen OBJECTIVE We evaluated whelther antithyroid drug treatment could be terminated more appropriately when both the serum basal thyrotrophin ( TSH ) level and TSH receptor antibody activity have become normal UNLABELLED Regardless the autoimmune origin of Graves ' disease , the preferred method of its treatment remains antithyroid drug administration . Use of immunosuppressive agents ( mostly steroids ) is still limited to the therapy of disease complications , such as proliferative ophthalmopathy . The aim of the study was to assess the influence of early immunosuppressive treatment of autoimmune thyrotoxicosis with azathioprine on the course of the disease and the incidence of its complications . The study comprised 64 patients ( 47 females and 17 males aged 20 - 43 years ) for the first time diagnosed with Graves ' disease . The subjects were r and omised into two groups . Group I consisted of 28 patients treated only with antithyroid drugs , the remaining 36 subjects additionally receiving azathioprine were included into group II . The dose of both drugs was adjusted during the treatment according to metabolic status of each patients . The treatment was continued for 8 - 14 months , the follow-up duration after therapy withdrawal was 5 years . Euthyreosis was achieved in all patients 2 - 8 weeks after treatment initiation . No drug intolerance symptoms were observed in group I. In four patients additionally treated with azathioprine , gastrointestinal side effects or leucopenia were present . The disease relapse was observed during the follow-up period in 15 ( 53.5 % ) patients of group I and in 3 ( 8.3 % ) of group II , the difference was statistically significant ( p<0.01 ) . Only one patient receiving additionally azathioprine presented ophthalmic symptoms compared with seven subjects ( 25 % ) treated only with antithyroid drugs ( p<0.001 ) . The patients of group I were also more frequently referred to surgical treatment due to rapid goitre growth ( accordingly 5 ( 17.8 % ) and 1 ( 2.7 % ) patients , p=0.07 ) , the difference between both groups not being statistically significant . CONCLUSIONS Additional early immunosuppressive treatment significantly decreased frequency of Graves ' disease complications and thyrotoxicosis recurrence . The use of azathioprine may be advised in patients with contraindications to the radical Graves ' disease treatment and in prophylaxis of its complications BACKGROUND Thionamide antithyroid drugs ( ATDs ) have certain disadvantages and are associated with some adverse events ( AEs ) . To overcome the problems associated with ATDs , a compound antithyroid ointment ( CATO ) containing methimazole ( MMI ) and hydrocortisone has been developed for use as a local thyroid treatment ( LTT ) . OBJECTIVE The aim of this study was to assess the clinical effectiveness and tolerability of CATO LTT in patients with Graves disease ( GD ) . METHODS This was a prospect i ve , r and omized , open-label , parallel-group clinical trial conducted at the Provincial Hospital Affiliated to Sh and ong University ( Jinan , China ) . Patients with GD aged 19 to 65 years were r and omized to receive either CATO LTT 0.3 g/d or oral MMI 37.5 mg/d ( control group ) treatment for 18 months , with a 4-year follow-up period . Hyperthyroid symptoms , thyroid function , granulocyte count , liver function , and AEs were assessed at baseline and every 2 weeks until serum thyroid hormone ( TH ) concentration normalized , at which point patients were assessed monthly . The primary efficacy end points were the duration of treatment required for serum TH concentration to normalize and the remission rate after completing the 18-month treatment regimen . RESULTS A total of 154 patients ( 133 women , 21 men ; mean [ SD ] age , 39.6 [ 11.8 ] years ; all Han Chinese ) participated in the study ; all patients completed the 18-month treatment period . Compared with the MMI group ( n 76 ) , the CATO- treated group ( n 78 ) had a significantly shorter median ( range ) time to restoration of normal serum thyroid hormone concentration ( 43 [ 12 - 150 ] vs 22 [ 7 - 60 ] days ; P < 0.001 ) , a significantly lower rate of recurrence of hyperthyroidism ( 309/1520 [ 20.3 % ] vs 193/1368 [ 14.1 % ] person-time ; P < 0.001 ) , a significantly lower drug hypothyroidism rate ( 185/1520 [ 12.2 % ] vs 54/1368 [ 3.9 % ] person-time ; P < 0.001 ) , and a higher remission rate ( year 1:46/69 [ 66.7 % ] vs 65/72 [ 90.3 % ] patients , P 0.001 ; year 2:40/69 [ 58.0 % ] vs 60/72 [ 83.3 % ] patients , P - 0.001 ; year 3:34/69 [ 49.3 % ] vs 57/72 [ 79.2 % ] patients , P < 0.001 ; and year 4:30/69 [ 43.5 % ] vs 55/72 [ 76.4 % ] patients , P < 0.001 ) . Systemic AEs occurred in 6 patients ( 7.9 % ) in the MMI group ( drug neutropenia , 2 patients [ 2.6 % ] ; epistaxis , 1 [ 1.3 % ] ; hepatopathy , 1 [ 1.3 % ] ; and other systemic AEs , 2 [ 2.6 % ] ) , while no systemic AEs were observed/reported in the CATO group . CONCLUSION This study suggests that CATO LTT was well tolerated and more effective than oral MMI treatment in controlling thyrotoxicosis and promoting remission of GD in these Han Chinese patients OBJECTIVE The optimal dosage regimen for carbimazole ( CBZ ) in the treatment of hyperthyroidism remains uncertain , despite clinical use of the drug for approximately fifty years . We have compared the early clinical and biochemical responses to 20 or 40 mg/day of CBZ given as initial treatment for hyperthyroidism |
12,469 | 20,451,274 | RESULTS Overall , ERBs are tolerated well , although patients with pre-existing anorectal disease have an increased risk of developing ERB-related toxicity .
Planning studies show reduced Rwall and anal wall ( Awall ) doses with ERB application .
ERBs seem well-tolerated and in planning studies reduce anorectal wall doses . | BACKGROUND AND PURPOSE Endorectal balloons ( ERBs ) are being used in prostate radiotherapy for prostate immobilization and rectal wall ( Rwall ) sparing .
Some of their aspects , however , have been question ed , like patient 's tolerance and their value in modern high-precision radiotherapy .
This paper gives an overview of published data concerning ERB application in prostate radiotherapy . | PURPOSE To investigate the set-up errors and deformation associated with daily placement of endorectal balloons in prostate radiotherapy . MATERIAL S AND METHODS Endorectal balloons were placed daily in 20 prostate cancer patients undergoing radiotherapy . Electronic portal images ( EPIs ) were collected weekly from anterior-posterior ( AP ) and lateral views . The EPIs were compared with digitally reconstructed radiographs from computed tomography scans obtained during pretreatment period to estimate displacements . The interfraction deformation of balloon was estimated with variations in diameter in three orthogonal directions throughout the treatment course . RESULTS A total of 154 EPIs were evaluated . The mean displacements of balloon relative to bony l and mark were 1.8 mm in superior-inferior ( SI ) , 1.3 mm in AP , and 0.1 mm in left-right ( LR ) directions . The systematic errors in SI , AP , and LR directions were 3.3 mm , 4.9 mm , and 4.0 mm , respectively . The r and om ( interfraction ) displacements , relative to either bony l and marks or treatment isocenter , were larger in SI direction ( 4.5 mm and 4.5 mm ) , than in AP ( 3.9 mm and 4.4 mm ) and LR directions ( 3.0 mm and 3.0 mm ) . The r and om errors of treatment isocenter to bony l and mark were 2.3 mm , 3.2 mm , and 2.6 mm in SI , AP , and LR directions , respectively . Over the treatment course , balloon deformations of 2.8 mm , 2.5 mm , and 2.6 mm occurred in SI , AP , and LR directions , respectively . The coefficient of variance of deformation was 7.9 % , 4.9 % , and 4.9 % in these directions . CONCLUSIONS Larger interfractional displacement and the most prominent interfractional deformation of endorectal balloon were both in SI direction PURPOSE To evaluate the Vienna Rectoscopy Score ( VRS ) as a feasible and effective tool for detecting and classifying pathologic changes in the rectal mucosa after radiotherapy ( RT ) for prostate cancer , and , also , to correlate its findings with the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group ( RTOG ) score for late rectal toxicity . METHODS AND MATERIAL S A total of 486 patients with localized prostate cancer underwent external-beam RT up to 70 or 74 Gy within an Austrian-German prospect i ve multicenter trial . In 166 patients , voluntary rectal sigmoidoscopy was performed before and at 12 and /or 24 months after RT . Pathologic findings such as telangiectasia , congested mucosa , and ulcers were grade d ( Grade s 0 - 3 ) and summarized according to the VRS . Late rectal side effects ( EORTC/RTOG ) were documented and correlated with the corresponding VRS . RESULTS Before RT , 99 % had a VRS score of 0 . The median follow-up was 40 months . Overall , a late rectal side effects grade or score 1 - 3 was detected in 43 % by EORTC/RTOG compared with 68 % by VRS ( p < 0.05 ) . Grade s 0 , 1 , 2 , and 3 late rectal side effects were found using EORTC/RTOG in 57 % , 11 % , 28 % , and 3 % , respectively ; the corresponding percentages were 32 % , 22 % , 32 % , and 14 % for a VRS of 0 , 1 , 2 , and 3 , respectively . A significant coherence between the VRS and EORTC/RTOG was found ( p < 0.01 ) . CONCLUSIONS The VRS is a feasible and effective tool for describing and classifying pathologic findings in the rectal mucosa after RT within a multicenter trial . The VRS and EORTC/RTOG showed a high coherence . However the VRS was significantly more sensitive A prostate treatment immobilization system was evaluated with respect to setup errors and efficiency for a specific treatment setup . Prostate patients were treated in the prone position with a rectal catheter using the NOMOS intensity modulated radiotherapy system . Immobilization and setup consisted of a Vac‐Lok ™ bag ( MED‐TEC , Orange City , IO ) fitted within a registration carrier box where patients were aligned to the bag using skin marks along the lower leg . Daily setup errors were analyzed using lateral portal films , registration plates mounted to the carrier box , and the pubic symphasis as a bony reference . Two studies were conducted to evaluate setup technique . In the first study , patient setup required 3–5 minutes for patient positioning and the corresponding superior/inferior errors were found to have a st and ard deviation of 3.5 mm . In the second study , the technique st and ards were reduced to allow for faster setup times and , consequently , larger errors ; setup times were 1–2 minutes and the mean and st and ard deviation errors were ~2 and 5 mm , respectively . PACS number(s ) : 87.53.–j , PURPOSE When > 25 % of the rectum is irradiated to > or = 70 Gy , the risk of developing Grade 2 or higher rectal complications is significantly increased . This study evaluates the impact on dose to the rectum from the use of an intrarectal ( IR ) balloon device , previously shown to immobilize the prostate gl and and localize the rectum , in patients receiving dose escalated 3-dimentional ( 3D ) conformal radiation therapy . MATERIAL S AND METHODS From July 2001 through February 2003 , 28 consecutive patients with prostate cancer underwent computerized tomography-based simulation with and without the IR balloon in place . Treatment planning was performed for three clinical paradigms in which the IR balloon was not used at all ( 0 Gy ) , used during the cone-down for 15 treatments ( 28.35 Gy ) , or used for the entire course of 40 treatments ( 75.6 Gy ) . The three plans were compared for differences in the percent of rectum receiving > 70 Gy . RESULTS Dose volume histogram ( DVH ) analysis revealed that the median(range ) of percent rectal volume exceeding 70 Gy was 25 % ( 12.7 - 41.5 % ) , 7.5 % ( 0.9 - 19.5 % ) , and 3.6 % ( 0 - 8.7 % ) for patients in whom the IR balloon was used for 0 , 15 , and 40 treatments , respectively . The percent of rectum exceeding 70 Gy was significantly different for all treatment plan comparisons ( P < 0.0001 ) . CONCLUSIONS Grade 2 or higher rectal toxicity may be minimized during dose escalated 3D conformal radiation therapy through the use of an IR balloon during the 3-week cone down portion of an 8-week treatment course Purpose : Evaluation of late side effects and biochemical control ( bNED ) 5 years after three-dimensional radiotherapy with moderate , risk-adapted dose escalation . Patients and Methods : From 03/1999 to 07/2002 , 486 patients have been registered in the prospect i ve Austrian-German multicenter phase II trial ( AUGE ) . 399 ( 82 % ) localized prostate cancer patients ( T1–3 Nx/N0 M0 ) were evaluated . The low- and intermediate-risk groups were treated with 70 Gy , the high-risk group with 74 Gy , respectively . Additional hormonal therapy ( HT ) was recommended for intermediate- and high-risk group patients . Late toxicity ( EORTC/RTOG ) and bNED ( ASTRO and Phoenix ) were prospect ively assessed . Results : Median follow-up was 65 months . Distribution concerning risk groups ( low- , intermediate- , high-risk group ) showed 29 % , 50 % and 21 % of patients , respectively . HT was given in 87 % of patients . The 5-year actuarial rates of late side effects grade ≥ 2 for 70 Gy/74 Gy were 28%/30 % ( gastrointestinal ; p = 0.73 ) and 19%/34 % ( urogenital ; p = 0,06 ) . The 5-year actuarial bNED rate stratified by risk groups ( low- , intermediate- , high-risk group ) was 74 % , 66 % and 50 % ( ASTRO ) , and 81 % , 80 % and 60 % ( Phoenix ) , respectively . Within multivariate analysis T-stage and initial prostate specific antigen were significant factors influencing bNED ( ASTRO ) whereas Gleason Score and duration of HT were not . Conclusion : Dose escalation within st and ard three-dimensional conformal radiotherapy ( 3D-CRT ) up to a level of 74 Gy did not result in significantly increased gastrointestinal side effects , whereas urogenital side effects showed an increase close to significance . However , the total number of patients with severe toxicity was low . To achieve high tumor control rates with acceptable treatment-related morbidity , local doses of at least 74 Gy should be considered , in particular for intermediate- or high-risk patients applying 3D-CRT.Ziel : Bestimmung von Spätnebenwirkungen und biochemischer Kontrolle ( bNED ) nach risikoadaptierter Dosiseskalation i m Rahmen einer prospektiven österreichisch-deutschen Phase-II-Multicenterstudie . Patienten und Method ik : Von 03/1999 bis 07/2002 wurden 486 Patienten mit Prostatakarzinom ( T1–3 Nx/N0 M0 ) gemeldet , und 399 ( 82 % ) kamen zur Auswertung . Patienten der Niedrig- und Intermediärrisikogruppe wurden mit 70 Gy , die Hochrisikogruppe mit 74 Gy bestrahlt ( Tabelle 1 ) . Eine begleitende Hormontherapie wurde für Patienten der Intermediär- und Hochrisikogruppe empfohlen . Spätnebenwirkungen ( EORTC/RTOG ) und bNED ( ASTRO/Phoenix ) wurden ermittelt . Ergebnisse : Der mittlere Nachbeobachtungszeitraum betrug 65 Monate . Hinsichtlich der Risikogruppen ( Niedrig- , Intermediär- , Hochrisikogruppe ) f and en sich 29 % , 50 % , und 21 % Patienten . Eine begleitende Hormontherapie erhielten 87 % der Patienten . Detaillierte Patienten date n sind in Tabelle 2 aufgeführt . Die 5-Jahres-Raten an Spätnebenwirkungen Grad ≥ 2 für 70 Gy/74 Gy lagen bei 28%/30 % ( gastrointestinal ; p = 0,73 ) und 19%/34 % ( urogenital ; p = 0,06 ; Abbildungen 1 und 2 ) . Die 5-Jahres-bNED-Raten entsprechend den Risikogruppen ( Niedrig- , Intermediär- , Hochrisikogruppe ) lagen bei 74 % , 66 % und 50 % ( ASTRO ; Abbildung 3 ) bzw . 81 % , 80 % und 60 % ( Phoenix ; Abbildung 4 ) . In der multivariaten Analyse zeigten sich T-Stadium und initiales prostataspezifisches Antigen als signifikant bezüglich bNED ( ASTRO ) und Gleason-Score sowie die Dauer der Hormontherapie als nicht signifikant ( Tabelle 4).Schlussfolgerung : Die Dosissteigerung auf 74 Gy führt zu keinen signifikant erhöhten Raten an gastrointestinalen Spätnebenwirkungen . Die Rate an urogenitalen Spätnebenwirkungen ist hingegen erhöht . Insgesamt finden sich jedoch nur wenige schwere Grad-3-Spätnebenwirkungen ( Tabelle 3 ) . Um respektable Tumorkontrollraten ( Abbildung 5 ) zu erreichen , sollte , vor allem für Patienten der Intermediär- und Hochrisikogruppe , eine lokale Dosis von zumindest 74 Gy appliziert werden PURPOSE To assess the benefit of escalating the dose in definitive prostate cancer radiotherapy vs. the associated risk of complications . MATERIAL S AND METHODS Between 1987 and 1999 , 1087 patients with clinical Stage T1b-T3 adenocarcinoma of the prostate were definitively irradiated without hormonal therapy and had a pretreatment serum prostate-specific antigen ( PSA ) and Gleason score recorded . The median follow-up was 65 months . Doses ranged from 64 to 78 Gy , with the treatment techniques corresponding to the year of therapy and the prescribed dose . A total of 301 patients were treated on a r and omized protocol to either 70 or 78 Gy . Also , 163 patients were treated with three-dimensional conformal therapy and had dose-volume histograms available for review . RESULTS Tumor stage , grade , pretreatment PSA level , and radiation dose were all independent predictors of PSA disease-free survival ( PSA-DFS ) in multivariate analysis . The hazard rate for biochemical failure peaked at 1.5 - 3 years after radiotherapy . Although a statistically significant dose effect on PSA-DFS was found in the pretreatment PSA levels of those with both < or = 10 ng/mL and > 10 ng/mL , in those with a pretreatment PSA < or = 10 ng/mL , the improvement in outcome was only seen going from a dose level of 64 - 66 Gy to 68 - 70 Gy with a 5-year PSA-DFS rate of 66 % vs. 81 % ( p < 0.0001 ) . This was also confirmed by the data from the r and omized patients who showed no difference in outcome whether treated to 70 Gy or 78 Gy . In patients with a pretreatment PSA level > 10 ng/mL , a statistically significant improvement was found in disease-free outcome among the 64 - 66-Gy , 68 - 70-Gy , and 78-Gy levels . PSA-DFS was approximately 50 % better at each higher dose level at 5 and 8 years after treatment . The dose had a statistically significant impact in both intermediate- and high-risk groups . Rectal morbidity was both dose and volume related . Although at 5 years after therapy , the Grade 2 - 3 rectal complication rate was twice as high for patients treated to 78 Gy than to 70 Gy , 26 % vs. 12 % , this risk could be markedly diminished by adhering to dose-volume constraints . CONCLUSIONS In intermediate- and high-risk prostate cancer patients , although it appears that radiation-dose escalation may improve PSA-DF outcome , the price paid in treatment morbidity can be high without adequate attention to dose-volume constraints of normal tissue . Care must be taken to consider not only the hazard of tumor recurrence but also that of complications Purpose : To prospect ively define the setup error and the interfraction prostate localization accuracy of the planning target volume ( PTV ) in the presence of an endorectal balloon ( ERB ) device . Patients and Methods : Weekly portal images ( PIs ) of 15 patients undergoing external-beam radiotherapy were analyzed . Displacements of the isocenter and the center of the ERB were measured . The setup and target motion variability were assessed with regard to the position variability of the ERB . Results : The setup error was r and om and target motion variability was largest in the craniocaudal direction . The mean displacement of the isocenter was 2.1 mm ( ± 1.2 mm SD [ st and ard deviation ] ) , 2.4 mm ( ± 2.2 mm SD ) , and 3.8 mm ( ± 4.0 mm SD ) in the left-right , craniocaudal , and anteroposterior directions , respectively ( p = 0.1 ) . The mean displacement of the ERB was 2.0 mm ( ± 1.4 mm SD ) , 4.1 mm ( ± 2.0 mm SD ) , and 3.8 mm ( ± 3.3 mm SD ; p = 0.03 ) . Setup margin and internal margin contributed equally to the PTV margin . Cumulative placement insecurity of the field and the ERB together was 4.0 mm ( ± 2.1 mm SD ) laterally , 6.4 mm ( ± 2.5 mm SD ) craniocaudally , and 7.7 mm ( ± 7.0 mm SD ) anteroposteriorly . The 95 % CIs ( confidence intervals ) were 2.9–5.2 mm , 5.1–7.8 mm , and 3.8–11.5 mm . In 35 % of cases , the estimation of the dorsal margin exceeded 1 cm . Conclusion : Margin estimate dorsally may exceed 1 cm and on-line position verification with an ERB can not be recommended for dose escalation > 70 Gy . Ziel : Analyse des Positionierungsfehlers und der Lokalisationsgenauigkeit der Prostata zwischen den Bestrahlungen unter der Verwendung eines endorektalen Ballons ( ERB ) zwecks Positionierungshilfe . Patienten und Method ik : Die sequentiellen Einstellungsaufnahmen von 15 Patienten , die in kurativer Absicht eine externe Radiotherapie erhielten , wurden analysiert . Die Positionierungsvariabilität des ERB wurde unter Berücksichtigung der Lagevariabilität des Set-up und des Zielvolumens gemessen . Ergebnisse : Der Einstellungsfehler ( systemischer Fehler ) zeigte keine Prädispositionen in x- , y- oder z-Richtung . Die Bewegungsvariabilität in kraniokaudaler Richtung war am größten . Die Lagevariabilität des Feldzentrums betrug 2,1 mm ( ± 1,2 mm ) , 2,4 mm ( ± 2,2 mm ) und 3,8 mm ( ± 4,0 mm ) in seitlicher , kraniokaudaler und anteroposteriorer Richtung ( p = 0,1 ) . Der ERB zeigte eine Lagevariabilität von 2 mm ( ± 1,4 mm ) , 4,1 mm ( ± 2,0 mm ) und 3,8 mm ( ± 3,3 mm ) seitlich , kraniokaudal und anteroposterior ( p = 0,03 ) . Die Positionsvariabilität des Feldzentrums in Bezug auf die Lokalisation des ERB war vernachlässigbar . Zur kumulativen Zielunsicherheit trugen der systemische und der spezifische Fehler gleichermaßen bei . Die durchschnittliche Lageunsicherheit des Feldes und des Ballons gemeinsam betrug 4,0 mm ( ± 2,1 mm ) lateral , 6,4 mm ( ± 2,5 mm ) kraniokaudal und 7,7 mm ( ± 7,0 mm ) anteroposterior . Die 95%-Konfidenzintervalle betrugen 2.9–5.2 mm , 5.1–7.8 mm , und 3.8–11.5 mm . Der geschätzte Sicherheitsabst and in dorsaler Richtung lag in 35 % der Fälle bei > 1 cm . Schlussfolgerung : Um einen Sicherheitsr and von < 1 cm gegen dorsal zu erzielen , reicht ein ERB allein nicht aus . Für Therapien mit Dosen > 70 Gy empfehlen sich zusätzliche Positionierungs- und Positionsverifikationssysteme , um den dorsalen Sicherheitsabst and klein halten zu können ZusammenfassungHINTERGRUND : In der 3 dimensionalen Radiotherapie des lokalisierten Prostatakarzinoms wird zur Fixierung der Prostata und zur Verminderung der Strahlendosis an der Rektumhinterw and ein Rektumballon verwendet . Ziel dieser Studie war die Evaluierung der klinischen Anwendbarkeit eines Rektumballonkatheters , dessen Patientenakzeptanz und Untersuchung des Einflusses von akuten rektalen Nebenwirkungen und prätherapeutisch detektierten Hämorrhoiden auf die Ballonverträglichkeit . MATERIAL UND METHOD E : 442 Patienten mit lokalisiertem Prostatakarzinom wurden i m Rahmen einer prospektiven österreichisch-deutschen Multicenter-Studie evaluiert . Die Gesamtherddosis betrug 70 bzw . 74 Gray . Die Ballonverträglichkeit ( 1 . Keine Beschwerden ; 2 . Schmerzen bei/während der Applikation ; 3 . Zeichen von Blut am Ballonkatheter nach Applikation ohne Schmerzen ; 4 . Zeichen von Blut am Ballonkatheter nach Applikation und Schmerzen ; 5 . Abbruch der Ballonapplikation ) und akuten rektalen Nebenwirkungen wurden während der Radiotherapie ( Beginn/Mitte/Ende ) ermittelt . 310 Patienten willigten in eine Rektoskopie vor Beginn der Therapie ein . RESULT ATE : 429/442 der Patienten ( 97 % ) wurden mit Rektumballon bestrahlt . Dabei berichteten 79 % über keine Beschwerden . Die Ballonapplikation musste bei nur 4 % der Patienten abgebrochen werden . Grad 0 akute rektale Nebenwirkungen f and en sich bei 52 % , Grad 1 bei 31 % , Grad 2 und 3 bei 17 % und 0,5 % . Es zeigte sich eine signifikante Korrelation zwischen Rektumballonbeschwerden und rektalen Nebenwirkungen ( p < 0,01 ) . Bei 36 % der Patienten f and en sich Hämorrhoiden ohne einen Einfluss auf die Ballonverträglichkeit zu zeigen . SCHLUSSFOLGERUNG : Der Rektumballon wird von einem Großteil der Patienten i m Rahmen der 3-dimensionalen Strahlentherapie des lokalisierten Prostatakarzinoms gut vertragen und kann i m klinischen Alltag sicher verwendet werden . Während Patienten mit akuten rektalen Nebenwirkungen signifikant häufiger über Beschwerden bzgl . des Rektumballonkatheters berichteten , zeigte das Vorliegen von Hämorrhoiden keinen Einfluss . Summary PURPOSE : Patients with localized prostate cancer are treated with 3D radiotherapy using a rectal balloon catheter for internal immobilization of the prostate , thereby reducing the radiation dose to the dorsal rectal wall . The purpose of the study was to investigate clinical feasibility and the influence of acute rectal side effects and pre-existing hemorrhoids on patients ' acceptance of the rectal balloon catheter . METHODS AND MATERIAL S : 442 patients who underwent primary radiation therapy for localized prostate cancer were included in this prospect i ve Austrian-German multicenter trial . The total radiation dose was either 70 Gy or 74 Gy . Acute rectal side effects were documented using the EORTC/RTOG grading score ( European Organisation for Research and Treatment of Cancer/Radiation Therapy 225 Oncology Group ) at weeks 2 , 4 and 7 of radiation treatment . Within the same time intervals patients were interviewed about their tolerance of the rectal balloon catheter , evaluating five categories of acceptance ( 1 = no major complaints , 2 = pain at/during application , 3 = signs of blood at the balloon catheter after application but without any pain , 4 = signs of blood at the balloon catheter after application and pain , 5 = balloon application had to be stopped ) . Voluntary rectoscopy prior to radiotherapy was performed in 310 patients . RESULTS : 429/442 patients ( 97 % ) were treated with the balloon catheter . No major complaints were reported in 79 % of the patients and no acute rectal side effects were seen in 52 % of the patients . Grade 1 side effects were seen in 31 % patients , Grade 2 in 17 % and Grade 3 in 0.5 % . Balloon use had to be stopped in only 4 % of the patients . There was significant correlation between balloon discomfort and rectal side effects ( p < 0.01 ) . The presence of hemorrhoids in 36 % patients prior to irradiation had no influence on balloon tolerance . CONCLUSIONS : The rectal balloon can be used in 3D radiotherapy of localized prostate cancer with a high degree of acceptance by the patients . Use of the balloon is safe within daily clinical treatment . Patients reporting acute rectal side effects experienced significantly more balloon discomfort , but the presence of hemorrhoids was not found to influence acceptance of the balloon PURPOSE The aim of this study was to investigate prospect ively the rectal wall ( Rwall ) spatial dose distribution , toxicity , and mucosal changes after prostate cancer radiotherapy with or without an endorectal balloon ( ERB ) . METHODS AND MATERIAL S A total of 24 patients with ERB and 24 without ERB ( No-ERB ) were treated with three-dimensional conformal radiotherapy ( 3D-CRT ) to a dose of 67.5 Gy . The Rwall was divided into 16 mucosal areas and Rwall dose surface maps were constructed . After 3 months , 6 months , 1 year , and 2 years a rectosigmoidoscopy was performed , and each mucosal area was scored on telangiectasia , congestion , ulceration , stricture , and necrosis . Late rectal toxicity was correlated with the endoscopic findings . RESULTS The ERB significantly reduced the Rwall volume exposed to doses > 40 Gy . Late rectal toxicity ( grade > or=1 , including excess of bowel movements and slight rectal discharge ) was reduced significantly in the ERB group . A total of 146 endoscopies and 2,336 mucosal areas were analyzed . Telangiectases were most frequently seen and appeared after 6 months . At 1 and 2 years , significantly less high- grade telangiectasia ( T 2 - 3 ) was observed in the ERB group at the lateral and posterior part of the Rwall . In mucosal areas exposed to doses > 40 Gy , less high- grade telangiectases ( T 2 - 3 ) were seen in the ERB group compared with the No-ERB group . CONCLUSIONS An ERB reduced the Rwall volume exposed to doses > 40 Gy , result ing in reduction of late rectal mucosal changes and reduced late rectal toxicity . Although further analysis is needed , these data suggest an ERB-induced increased tolerance for late Rwall damage OBJECTIVES To estimate the rates of rectal bleeding after dose-escalated three-dimensional conformal radiation therapy ( 3D-CRT ) on a prospect i ve , Phase II study in which a modified intrarectal balloon was used for prostate gl and localization and immobilization . METHODS The study cohort comprised 100 men with biopsy-proven adenocarcinoma of the prostate and at least one high-risk feature ( prostate-specific antigen level greater than 10 ng/mL , Gleason score 7 or higher , or clinical or radiographic T3 disease ) . Treatment consisted of and rogen suppression therapy and four-field 3D-CRT with an intrarectal balloon for the initial 15 treatments . Planning treatment volume dose was 75.6 Gy . The primary endpoint of time to grade 3 rectal bleeding was estimated with the Kaplan-Meier method for 57 men with a minimum follow-up of 1 year . RESULTS For 57 men with a median ( range ) follow-up of 1.8 ( 1.0 to 3.3 ) years , the median ( range ) volume of rectum exceeding 70 Gy was 3.7 ( 0.6 to 14.7 ) cm3 , and the 2-year estimate of grade 3 rectal bleeding rate was 10 % . This rate was 100 % as compared with 0 ( P < 0.0001 ) for men who were taking warfarin ( n = 3 ) or high-dose aspirin ( n = 1 ) as compared with neither , respectively . All grade 3 rectal bleeding events were controlled with argon plasma coagulation . CONCLUSIONS Dose-escalated 3D-CRT with an intrarectal balloon technique for prostate localization and immobilization produced no measurable grade 3 rectal bleeding unless the patient was taking anticoagulants PURPOSE A prospect i ve comparative study of a subset of 10 consecutive patients was performed , to describe the effects of an air-inflated rectal balloon tube that has been used for prostate immobilization in 360 patients since 1994 . In particular , influences on prostate motion , rectum filling variations , and dose-volume histograms ( DVHs ) of the rectum during a course of conformal radiotherapy were investigated . METHODS AND MATERIAL S Computed tomographic ( CT ) examinations without and with rectal balloon ( filled with 40 mL air ) were performed at the start ( t(0 ) ) , middle ( t(mi ) ) , and end of treatment ( t(e ) ) , result ing in 6 CT scans for each patient . Prostate displacement was measured from a lateral beam's-eye-view . DVHs of rectum as a solid organ , and anterior , posterior , and whole rectum wall were calculated at t(0 ) , t(mi ) , and t(e ) , and variations during treatment were analyzed for both examinations , with and without balloon . RESULTS By use of the balloon , rectum filling variations ( p = 0.04 ) and maximum anterior-posterior displacements of the prostate ( p = 0.008 ) were reduced significantly , leading to a reduction in DVH variations during treatment . Maximum displacements of posterior prostate border ( > 5 mm ) were found in 8/10 patients without a rectum balloon and in only 2/10 patients with the balloon . The balloon led to a significant reduction in partial posterior rectal wall volumes included in the high-dose regions , without significant changes at the anterior rectum wall in cases of irradiation of the prostate only . However , when entirely irradiating the whole seminal vesicles , this advantage was lost . CONCLUSIONS The rectal balloon catheter represents a simple technique to immobilize the prostate and to determine the position of the anterior rectal wall at daily treatment . This allows a reduction of margins , because of reduced prostate movement during treatment course BACKGROUND Radical radiotherapy is commonly used to treat localised prostate cancer . Late chronic side-effects limit the dose that can be given , and may be linked to the volume of normal tissues irradiated . Conformal radiotherapy allows a smaller amount of rectum and bladder to be treated , by shaping the high-dose volume to the prostate . We assessed the ability of this new technology to lessen the risk of radiation-related effects in a r and omised controlled trial of conformal versus conventional radiotherapy . METHODS We recruited men with prostate cancer for treatment with a st and ard dose of 64 Gy in daily 2 Gy fractions . The men were r and omly assigned conformal or conventional radiotherapy treatment . The primary endpoint was the development of late radiation complications ( > 3 months after treatment ) measured with the Radiation Therapy and Oncology Group ( RTOG ) score . Indicators of disease ( cancer ) control were also recorded . FINDINGS In the 225 men treated , significantly fewer men developed radiation-induced proctitis and bleeding in the conformal group than in the conventional group ( 37 vs 56 % > or = RTOG grade 1 , p=0.004 ; 5 vs 15 % > or = RTOG grade 2 , p=0.01 ) . There were no differences between groups in bladder function after treatment ( 53 vs 59 % > or = grade 1 , p=0.34 ; 20 vs 23 % > or = grade 2 , p=0.61 ) . After median follow-up of 3.6 years there was no significant difference between groups in local tumour control ( conformal 78 % [ 95 % CI 66 - 86 ] , conventional 83 % [ 69 - 90 ] ) . INTERPRETATION Conformal techniques significantly lowered the risk of late radiation-induced proctitis after radiotherapy for prostate cancer . Widespread introduction of these radiotherapy treatment methods is appropriate . Our results are the basis for dose-escalation studies to improve local tumour control Purpose : To report patient tolerance and acute anorectal toxicity of an endorectal balloon used for prostate immobilization during 35 daily fractions . Material s and Methods : The records of 396 patients treated for prostate cancer from October 1997 to November 2001 were review ed . Patients were treated with intensity modulated radiation therapy ( IMRT ) . Endorectal balloon catheter was inserted daily , inflated with 100 mL of air for immobilizing the prostate gl and . Patient and treatment factors were analyzed . Patients received a mean dose of 77 Gy/35 fractions/7 weeks with no rectal block . Results : None of the 396 patients halted treatment because of associated ano-rectal toxicity . No patient stated that he would decline to be treated again with rectal balloon . Three of 396 ( 0.8 % ) patients required a reduction in the volume of the balloon to 50 mL. Seventeen of 396 ( 4.3 % ) patients required Lidocaine jelly with the insertion of balloon . Radiation Therapy Oncology Group ( RTOG ) grade s 1 and 2 rectal toxicity occurred in 55/396 ( 13.9 % ) and 73/396 ( 18.4 % ) , respectively . No RTOG grade 3 or 4 toxicities occurred . Topical anal medications were prescribed for 46 of 396 ( 11.6 % ) patients and antidiarrhea medication for 27 of 396 ( 6.8 % ) patients . Of patients with pretreatment anorectal disease , 50 % developed rectal toxicities over the 7 weeks . Rectal toxicity occurred most frequently in the third , fourth , fifth , or sixth week ; 19.5 % , 20.8 % , 18.2 % , and 16.9 % , respectively . The duration of the toxicity measured lasted 1 week , 35.2 % ; 2 weeks , 31.0 % ; 3 weeks , 15.5 % ; 4 weeks , 11.3 % ; 5 weeks , 4.2 % ; and 6 weeks , 2.8 % . Conclusion : Most of the patients , 393/396 ( 99.2 % ) , tolerated a 100 mL endorectal immobilization balloon for IMRT . The rate of acute anorectal toxicity was acceptable with no grade 3 or 4 toxicities . Duration of the toxicities typically was 1 to 2 weeks . Patients with pre-existing anorectal disease are at higher risk of developing acute anorectal toxicity with the use of an endorectal balloon PURPOSE To investigate the effect of an endorectal balloon ( ERB ) and an off-line correction protocol on the day-to-day , interfraction prostate gl and motion , in patients receiving external beam radiotherapy for prostate cancer . METHODS AND MATERIAL S In 22 patients , irradiated with an ERB in situ ( ERB group ) and in 30 patients without an ERB ( No-ERB group ) , prostate displacements were measured daily in three orthogonal directions with portal images . Implanted gold markers and an off-line electronic portal imaging correction protocol were used for prostate position verification and correction . Movie loops were analyzed to evaluate prostate motion and rectal filling variations . RESULTS The off-line correction protocol reduced the systematic prostate displacements , equally for the ERB and No-ERB group , to 1.3 - 1.8 mm ( 1 SD ) . The mean 3D displacement was reduced to 2.8 mm and 2.4 mm for the ERB and No-ERB group , respectively . The r and om interfraction displacements , relative to the treatment isocenter , were not reduced by the ERB and remained nearly unchanged in all three directions : 3.1 mm ( 1 SD ) left-right , 2.6 mm ( 1 SD ) superior-inferior , and 4.7 mm ( 1 SD ) for the anterior-posterior direction . These day-to-day prostate position variations can be explained by the presence of gas and stool beside the ERB . CONCLUSIONS The off-line corrections on the fiducial markers are effective in reducing the systematic prostate displacements . The investigated ERB does not reduce the interfraction prostate motion . Although the overall mean displacement is low , the day-to-day interfraction motion , especially in anterior-posterior direction , remains high compared with the systematic displacements PURPOSE This communication reports the long-term results of the original group of prostate cancer patients who participated in the first prospect i ve Fox Chase Cancer Center radiation dose escalation study for which 8 - 12 years of follow-up is now available . METHODS AND MATERIAL S Between March 1 , 1989 and October 31 , 1992 , 232 patients with clinical ly localized prostate cancer received three-dimensional conformal radiotherapy only at Fox Chase Cancer Center in a prospect i ve dose-escalation study . Of these patients , 229 were assessable . The 8- , 10- , and 12-year actuarial rates of biochemical control ( biochemically no evidence of disease [ bNED ] ) , freedom from distant metastasis ( FDM ) , and morbidity were calculated . The Cox proportional hazards model was used to assess multivariately the predictors of bNED control and FDM , including pretreatment prostate-specific antigen ( PSA ) level ( continuous ) , tumor stage ( T1/T2a vs. T2b/T3 ) , Gleason score ( 2 - 6 vs. 7 - 10 ) , and radiation dose ( continuous ) . The median total dose for all patients was 74 Gy ( range 67 - 81 ) . The median follow-up for living patients was 110 months ( range 89 - 147 ) . bNED control was defined using the American Society for Therapeutic Radiology and Oncology consensus definition . RESULTS The actuarial bNED control for all patients included in this series was 55 % at 5 years , 48 % at 10 years , and 48 % at 12 years . Patients with pretreatment PSA levels of 10 - 20 ng/mL had statistically significant differences ( 19 % vs. 31 % vs. 84 % , p = 0.0003 ) in bNED control when stratified by dose ( < 71.5 , 71.5 - 75.6 , and > 75.6 Gy , respectively ) on univariate analysis . For the 229 patients with follow-up , 124 ( 54 % ) were clinical ly and biochemically without evidence of disease . Sixty-nine patients were alive at the time of last follow-up , and 55 patients were dead of intercurrent disease . On multivariate analysis , radiation dose was a statistically significant predictor of bNED control for all patients and for unfavorable patients with a pretreatment PSA < 10 ng/mL. For the patients with a pretreatment PSA level of 10 - 20 ng/mL , the radiation dose was a statistically significant predictor across all groups . No radiation dose response was seen for those patients with a pretreatment PSA level > 20 ng/mL , although large numbers of patients are required to demonstrate a difference . The radiation dose , Gleason score , and palpation T stage were significant predictors for the entire patient set , as well as for those with pretreatment PSA levels between 10 and 20 ng/mL. The FDM rate for all patients included in this series was 89 % , 83 % , and 83 % at 5 , 10 , and 12 years , respectively . For patients with pretreatment PSA levels < 10 ng/mL , all four covariates ( radiation dose , Gleason score , pretreatment PSA , and palpation T stage ) were significant predictors of distance metastasis . Using the Radiation Therapy Oncology Group morbidity scale , no difference was noted in the frequency of Grade 2 and 3 genitourinary and Grade 3 gastrointestinal morbidity when patients in this data set were stratified by radiation dose . However , a significant increase occurred in Grade 2 gastrointestinal complications as the radiation dose increased . CONCLUSION The long-term results of the original Fox Chase radiation dose escalation study with > 9 years of median follow-up confirm the existence of a dose response for both bNED control and FDM . The dose response in prostate cancer is real , and the absence of biochemical recurrence after 8 years demonstrates the lack of late failure and suggests cure |
12,470 | 30,244,786 | The narrative synthesis suggested that interventions have the potential to reduce sitting time in non-working older adults . | Sedentary behavior has been found to be associated with negative health outcomes independently of physical activity in older adults .
This systematic review collates interventions to reduce sedentary behavior in non-working older adults , assessing whether they are effective , feasible , and safe . | Objective : To compare the effects of behavioral interventions targeting decreased sedentary behavior versus increased moderate-to-vigorous intensity physical activity ( MVPA ) in older adults . Method : Inactive older adults ( N = 38 , 68 ± 7 years old , 71 % female ) were r and omized to 12-week interventions targeting decreased sedentary behavior ( Sit Less ) or increased MVPA ( Get Active ) . The SenseWear armb and was used to objective ly assess activity in real time . Assessment s included a blinded armb and , the Community Health Activites Model Program for Senior ( CHAMPS ) question naire , 400-meter walk , and the Short Physical Performance Battery ( SPPB ) . Results : Objective ly measured MVPA increased in Get Active ( 75 ± 22 min/week , p < .001 ) ; self-reported MVPA increased in both groups ( p < .05 ) . Sedentary behavior did not change in either group ( all p > .05 ) . Only the Sit Less group improved the SPPB score ( 0.5 ± 0.3 , p = .046 ) . Discussion : Targeting reduced sedentary behavior had a greater effect on physical function among inactive but high functioning older adults over 12 weeks . Future studies of longer duration and combining increased MVPA with reduced sedentary behavior are needed PURPOSE Although moderate-to-vigorous physical activity is related to premature mortality , the relationship between sedentary behaviors and mortality has not been fully explored and may represent a different paradigm than that associated with lack of exercise . We prospect ively examined sitting time and mortality in a representative sample of 17,013 Canadians 18 - 90 yr of age . METHODS Evaluation of daily sitting time ( almost none of the time , one fourth of the time , half of the time , three fourths of the time , almost all of the time ) , leisure time physical activity , smoking status , and alcohol consumption was conducted at baseline . Participants were followed prospect ively for an average of 12.0 yr for the ascertainment of mortality status . RESULTS There were 1832 deaths ( 759 of cardiovascular disease ( CVD ) and 547 of cancer ) during 204,732 person-yr of follow-up . After adjustment for potential confounders , there was a progressively higher risk of mortality across higher levels of sitting time from all causes ( hazard ratios ( HR ) : 1.00 , 1.00 , 1.11 , 1.36 , 1.54 ; P for trend < 0.0001 ) and CVD ( HR:1.00 , 1.01 , 1.22 , 1.47 , 1.54 ; P for trend < 0.0001 ) but not cancer . Similar results were obtained when stratified by sex , age , smoking status , and body mass index . Age-adjusted all-cause mortality rates per 10,000 person-yr of follow-up were 87 , 86 , 105 , 130 , and 161 ( P for trend < 0.0001 ) in physically inactive participants and 75 , 69 , 76 , 98 , 105 ( P for trend = 0.008 ) in active participants across sitting time categories . CONCLUSIONS These data demonstrate a dose-response association between sitting time and mortality from all causes and CVD , independent of leisure time physical activity . In addition to the promotion of moderate-to-vigorous physical activity and a healthy weight , physicians should discourage sitting for extended periods AIM To compare the effect of 7 h of prolonged sitting on resting blood pressure with a similar duration of sitting combined with intermittent brief bouts of light-intensity or moderate-intensity physical activity . METHODS AND RESULTS Overweight/obese adults ( n = 19 ; aged 45 - 65 years ) were recruited for a r and omized three-treatment crossover trial with a one-week washout between treatments : 1 ) uninterrupted sitting ; 2 ) sitting with 2 min bouts of light-intensity walking at 3.2 km/h every 20 min ; and , 3 ) sitting with 2 min bouts of moderate-intensity walking at between 5.8 and 6.4 km/h every 20 min . After an initial 2 h period seated , participants consumed a test meal ( 75 g carbohydrate , 50 g fat ) and completed each condition over the next 5 h. Resting blood pressure was assessed oscillometrically every hour as a single measurement , 5 min prior to each activity bout . GEE models were adjusted for sex , age , BMI , fasting blood pressure and treatment order . After adjustment for potential confounding variables , breaking up prolonged sitting with light and moderate-intensity activity breaks was associated with lower systolic blood pressure [ light : 120 ± 1 mmHg ( estimated marginal mean ± SEM ) , P = 0.002 ; moderate : 121 ± 1 mmHg , P = 0.02 ] , compared to uninterrupted sitting ( 123 ± 1 mmHg ) . Diastolic blood pressure was also significantly lower during both of the activity conditions ( light : 76 ± 1 mmHg , P = 0.006 ; moderate : 77 ± 1 mmHg , P = 0.03 ) compared to uninterrupted sitting ( 79 ± 1 mmHg ) . No significant between-condition differences were observed in mean arterial pressure or heart rate . CONCLUSION Regularly breaking up prolonged sitting may reduce systolic and diastolic blood pressure . TRIAL REGISTRATION NUMBER ACTRN12609000656235 ( http://www.anzctr.org.au ) TRIAL REGISTRATION DATE : August 4th 2009 Background Excessive sitting has been linked to poor health . It is unknown whether reducing total sitting time or increasing brief sit-to-st and transitions is more beneficial . We conducted a r and omized pilot study to assess whether it is feasible for working and non-working older adults to reduce these two different behavioral targets . Methods Thirty adults ( 15 workers and 15 non-workers ) age 50–70 years were r and omized to one of two conditions ( a 2-hour reduction in daily sitting or accumulating 30 additional brief sit-to-st and transitions per day ) . Sitting time , st and ing time , sit-to-st and transitions and stepping were assessed by a thigh worn inclinometer ( activPAL ) . Participants were assessed for 7 days at baseline and followed while the intervention was delivered ( 2 weeks ) . Mixed effects regression analyses adjusted for days within participants , device wear time , and employment status . Time by condition interactions were investigated . Results Recruitment , assessment s , and intervention delivery were feasible . The ‘ reduce sitting ’ group reduced their sitting by two hours , the ‘ increase sit-to-st and ’ group had no change in sitting time ( p < .001 ) . The sit-to-st and transition group increased their sit-to-st and transitions , the sitting group did not ( p < .001 ) . Conclusions This study was the first to demonstrate the feasibility and preliminary efficacy of specific sedentary behavioral goals . Trial Registration clinical trials.gov Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Background . Overweight and obese older adults have high sedentary time . We tested the feasibility and preliminary effects of a sedentary time reduction intervention among adults over age 60 with a body mass index over 27 kg/m2 using a nonr and omized one-arm design . Methods . Participants ( N = 25 , mean age = 71.4 , mean body mass index = 34 ) completed an 8-week theory-based intervention targeting reduced total sitting time and increased sit-to-st and transitions . An inclinometer ( activPAL ™ ) measured the primary outcomes , change in total sitting time and sit-to-st and transitions . Secondary outcomes included physical activity ( ActiGraph GT3X+ accelerometer ) , self-reported sedentary behaviors , physical function ( Short Physical Performance Battery ) , depressive symptoms ( 8-item Patient Health Question naire ) , quality of life ( PROMIS ) , and study satisfaction . Paired t tests examined pre – post test changes in sitting time , sit-to-st and transitions , and secondary outcomes . Results . Inclinometer measured sitting time decreased by 27 min/day ( p < .05 ) and sit-to-st and transitions increased by 2 per day ( p > .05 ) , while st and ing time increased by 25 min/day ( p < .05 ) . Accelerometer measured sedentary time , light-intensity , and moderate-to-vigorous physical activity improved ( all p values ≤ .05 ) . Self-reported sitting time , gait speed , and depressive symptoms also improved ( all p values < .05 ) . Effect sizes were small . Study satisfaction was high . Conclusions . Reducing sitting time is feasible , and the intervention shows preliminary evidence of effectiveness among older adults with overweight and obesity . R and omized trials of sedentary behavior reduction in overweight and obese older adults , most of whom have multiple chronic conditions , may be promising Older adults represent the segment of the population that sits the most . This study evaluated the feasibility , acceptability , safety , and preliminary efficacy of an intervention to reduce sedentary behavior ( SB ) in older adults that can be disseminated broadly for limited cost and delivered by paraprofessionals with limited training . Senior centers in Central Pennsylvania were r and omized to receive one of two healthy aging programs ( i.e. , intervention or comparison ) . Participants in both groups attended three 90-min meetings over 2 weeks . Behavior change content was delivered at the second session ( i.e. , day 7 ) . Forty-two participants ( nintervention = 25 , ncomparison = 17 ) were recruited from five senior centers . Content for the intervention group focused on reducing SB while comparison group content focused on reducing social isolation . Self-reported SB was assessed on days 7 and 14 . Repeated- measures ANOVA revealed a significant group × time interaction for total and weekday , but not weekend , SB . In the week following the delivery of group content , participants in the intervention group reported an average decrease in total SB of 837.8 min/week ; however , the comparison group reported a nonsignificant average decrease of 263.0 min/week of total SB . Participants in the intervention group also reported an average decrease in weekday SB of 132.6 min/weekday ( d = −0.83 ) in the week following the delivery of group content ; however , the comparison group reported a nonsignificant decrease of 24.0 min/weekday ( d = −0.16 ) . There were no significant changes in weekend SB in either group in the week following the delivery of group content . Participants ’ attendance , measurement completion , and program ratings were high . Safety issues were minimal . This intervention was feasible to implement and evaluate , acceptable to older adults , and showed promise for reducing older adults ’ SB OBJECTIVE To test the safety , feasibility , and effectiveness of reducing sitting time in stroke survivors . DESIGN R and omized controlled trial with attention-matched controls and blinded assessment s. SETTING Community . PARTICIPANTS Stroke survivors ( N=35 ; 22 men ; mean age , 66.9±12.7y ) . INTERVENTIONS Four counseling sessions over 7 weeks with a message of sit less and move more ( intervention group ) or calcium for bone health ( attention-matched control group ) . MAIN OUTCOME MEASURES Measures included safety ( adverse events , increases in pain , spasticity , or fatigue ) and feasibility ( adherence to trial protocol ) . Secondary measures included time spent sitting ( including in prolonged bouts ≥30min ) , st and ing , and stepping as measured by the thigh-worn inclinometer ( 7d , 24h/d protocol ) and time spent in physical activity of at least moderate intensity as measured by a triaxial accelerometer . The Multimedia Activity Recall for Children and Adults was used to describe changes in use of time . RESULTS Thirty-three participants completed the full protocol . Four participants reported falls during the intervention period with no other adverse events . From a baseline average of 640.7±99.6min/d , daily sitting time reduced on average by 30±50.6min/d ( 95 % confidence interval [ CI ] , 5.8 - 54.6 ) in the intervention group and 40.4±92.5min/d in the control group ( 95 % CI , 13.0 - 93.8 ) . Participants in both groups also reduced their time spent in prolonged sitting bouts ( ≥30min ) and increased time spent st and ing and stepping . CONCLUSIONS Our protocol was both safe and feasible . Participants in both groups spent less time sitting and more time st and ing and stepping postintervention , but outcomes were not superior for intervention participants . Attention matching is desirable in clinical trials and may have contributed to the positive outcomes for control participants PURPOSE Prolonged sitting has emerged as a risk factor for early mortality , but the extent of benefit realized by replacing sitting time with exercise or activities of everyday living ( i.e. , nonexercise activities ) is not known . METHODS We prospect ively followed 154,614 older adults ( 59 - 82 yr ) in the National Institutes of Health-AARP Diet and Health Study who reported no major chronic diseases at baseline and reported detailed information about sitting time , exercise , and nonexercise activities . Proportional hazard models were used to estimate adjusted hazard ratios and 95 % confidence intervals ( HR ( 95 % confidence interval ) ) for mortality . An isotemporal modeling approach was used to estimate associations for replacing sitting time with specific types of physical activity , with separate models fit for less active and more active participants to account for nonlinear associations . RESULTS During 6.8 yr ( SD , 1.0 ) of follow-up , 12,201 deaths occurred . Greater sitting time ( ≥12 vs < 5 h·d(-1 ) ) was associated with increased risk for all-cause and cardiovascular mortality . In less active adults ( < 2 h·d(-1 ) total activity ) , replacing 1 h·d(-1 ) of sitting with an equal amount of activity was associated with lower all-cause mortality for both exercise ( HR , 0.58 ( 0.54 - 0.63 ) ) and nonexercise activities ( HR , 0.70 ( 0.66 - 0.74 ) ) , including household chores , lawn and garden work , and daily walking . Among more active participants ( 2 + h·d(-1 ) total activity ) , replacement of sitting time with purpose ful exercise was associated with lower mortality ( HR , 0.91 ( 0.88 - 0.94 ) ) but not with nonexercise activity ( HR , 1.00 ( 0.98 - 1.02 ) ) . Similar results were noted for cardiovascular mortality . CONCLUSIONS Physical activity intervention strategies for older adults often focus on aerobic exercise , but our findings suggest that reducing sitting time and engaging in a variety of activities is also important , particularly for inactive adults |
12,471 | 30,270,428 | The evidence is currently inadequate to assess the safety and efficacy of exercise-based CR for people with implantable VADs compared with usual care . | BACKGROUND Heart failure is the end stage of heart disease , and the prevalence and incidence of the condition is rapidly increasing .
Although heart transplantation is one type of surgical treatment for people with end-stage heart failure , donor availability is limited .
Implantable ventricular assist devices ( VADs ) therefore offer an alternative treatment to heart transplantation .
OBJECTIVES To determine the benefits and harms of exercise-based CR for people with implantable VADs . | BACKGROUND As left ventricular assist device ( LVAD ) support duration increases , quality of life ( QoL ) becomes a concern . We review ed the QoL in patients on LVAD support for > or=1 year . METHODS We retrospectively review ed our prospect i ve data base for patients supported > or=1 year by HeartMate pulsatile- ( HM1 ) or continuous-flow ( HM2 ) LVADs from 2000 to 2009 . Transplant or death before 1 year merited exclusion . Metabolic equivalents of tasks ( METs ) , the Minnesota Living with Heart Failure Question naire ( MLHFQ ) , the 6-minute walk distance ( 6MWD ) , and New York Heart Association ( NYHA ) class were review ed . Complications and re-admissions were assessed . RESULTS Thirty patients were supported for > or=1 year ( 7 HM1s , 23 HM2s ) . Mean support duration was 594 + /- 173 days . Mean QoL metrics/functional status indicators at 12 months were : 6MWD , 393 + /- 290 m ; MET tolerance , 3.3 + /- 1 ; MLHFQ , 35 + /- 31 ; and NYHA , 1.4 + /- 0.6 . Mean re-admissions/year was 2.9 + /- 2 , with a duration of 13.8 + /- 21 days . Three patients were never re-admitted . Mean out-of-hospital time was 471 + /- 172 days ( 87.3 % of days ) . Infectious complications led to 43 % of re-admissions and occurred in the : drive-line ( 47 % ) at 442 + /- 236 days ; blood ( 37 % ) at 472 + /- 257 days ; and LVAD pocket ( 20 % ) at 550 + /- 202 days . Twenty-three patients ( 77 % ) required additional operations ( 1.7 + /- 1.8/year ) . The most common indication was drive-line infection , but ranged from ischemic bowel to defibrillator exchange . Eight required LVAD exchanges for mechanical ( n = 4 ) , electrical ( n = 3 ) , and thrombotic ( n = 1 ) issues . CONCLUSIONS Although LVAD support is not without complications , patients spend the majority of time outside the hospital enjoying a good quality of life Background : Capacity to exercise may not be fully restored in patients with heart failure even in the long term after ventricular assist device ( VAD ) implantation . The benefits of exercise training in patients with VAD are unknown . Design and methods : Fifteen patients , aged 38.3 ± 15.9 years , bridged to heart transplantation with left ventricular assist device or biventricular assist device were r and omized at a ratio of 2 : 1 to a training group ( TG , n = 10 ) or a control group ( n = 5 ) , 6.3 ± 4 months after implantation . Both the groups were advised to walk 30–45 min/day . TG also underwent moderate-intensity aerobic exercise using a bike or treadmill for 45 min , three to five times a week , combined with high-intensity inspiratory muscle training using a computer- design ed software to respiratory exhaustion , two to three times a week for 10 weeks . The patients were tested using cardiopulmonary exercise testing , 6-min walk test , spirometry and electronic pressure manometer for inspiratory muscle strength ( Pimax ) and endurance ( sustained Pimax ) measurement . Quality of life was assessed with the Minnesota Living with Heart Failure question naire . Results : TG improved peak oxygen consumption ( 19.3 ± 4.5 vs. 16.8 ± 3.7 ml/kg per min , P = 0.008 ) and VO2 at ventilatory threshold ( 15.1 ± 4.2 vs. 12 ± 5.6 ml/kg per min , P = 0.01 ) , whereas the ventilation/carbon dioxide slope decreased ( 35.9 ± 5.6 vs. 40 ± 6.5 , P = 0.009 ) . The 6-min walk test distance increased ( 527 ± 76 vs. 462 ± 88 m , P = 0.005 ) and quality of life was improved ( 38.2 ± 11.6 vs. 48.9 ± 12.8 , P = 0.005 ) , as well as Pimax ( 131.8 ± 33 vs. 95.5 ± 28cmH2O , P = 0.005 ) , sustained Pimax ( 484 ± 195 vs. 340 ± 193cmH2O/s/10 3 , P = 0.005 ) , and inspiratoty lung capacity ( 2.4 ± 0.9 vs. 1.7 ± 0.7 L , P = 0.008 ) were improved . No significant changes were noted in the control group . Conclusion : Our findings indicate that exercise training may improve the functional status of VAD recipients even at a later period after implantation and thus , may have additional importance in cases of destination therapy OBJECTIVES The authors sought to provide the pre-specified primary endpoint of the ROADMAP ( Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients ) trial at 2 years . BACKGROUND The ROADMAP trial was a prospect i ve nonr and omized observational study of 200 patients ( 97 with a left ventricular assist device [ LVAD ] , 103 on optimal medical management [ OMM ] ) that showed that survival with improved functional status at 1 year was better with LVADs compared with OMM in a patient population of ambulatory New York Heart Association functional class IIIb/IV patients . METHODS The primary composite endpoint was survival on original therapy with improvement in 6-min walk distance ≥75 m. RESULTS Patients receiving LVAD versus OMM had lower baseline health-related quality of life , reduced Seattle Heart Failure Model 1-year survival ( 78 % vs. 84 % ; p = 0.012 ) , and were predominantly INTERMACS ( Interagency Registry for Mechanically Assisted Circulatory Support ) profile 4 ( 65 % vs. 34 % ; p < 0.001 ) versus profiles 5 to 7 . More LVAD patients met the primary endpoint at 2 years : 30 % LVAD versus 12 % OMM ( odds ratio : 3.2 [ 95 % confidence interval : 1.3 to 7.7 ] ; p = 0.012 ) . Survival as treated on original therapy at 2 years was greater for LVAD versus OMM ( 70 ± 5 % vs. 41 ± 5 % ; p < 0.001 ) , but there was no difference in intent-to-treat survival ( 70 ± 5 % vs. 63 ± 5 % ; p = 0.307 ) . In the OMM arm , 23 of 103 ( 22 % ) received delayed LVADs ( 18 within 12 months ; 5 from 12 to 24 months ) . LVAD adverse events declined after year 1 for bleeding ( primarily gastrointestinal ) and arrhythmias . CONCLUSIONS Survival on original therapy with improvement in 6-min walk distance was superior with LVAD compared with OMM at 2 years . Reduction in key adverse events beyond 1 year was observed in the LVAD group . The ROADMAP trial provides risk-benefit information to guide patient- and physician-shared decision making for elective LVAD therapy as a treatment for heart failure . ( Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients [ ROADMAP ] ; NCT01452802 ) BACKGROUND Implantable left ventricular assist devices have benefited patients with end-stage heart failure as a bridge to cardiac transplantation , but their long-term use for the purpose of enhancing survival and the quality of life has not been evaluated . METHODS We r and omly assigned 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device ( 68 patients ) or optimal medical management ( 61 ) . All patients had symptoms of New York Heart Association class IV heart failure . RESULTS Kaplan-Meier survival analysis showed a reduction of 48 percent in the risk of death from any cause in the group that received left ventricular assist devices as compared with the medical-therapy group ( relative risk , 0.52 ; 95 percent confidence interval , 0.34 to 0.78 ; P=0.001 ) . The rates of survival at one year were 52 percent in the device group and 25 percent in the medical-therapy group ( P=0.002 ) , and the rates at two years were 23 percent and 8 percent ( P=0.09 ) , respectively . The frequency of serious adverse events in the device group was 2.35 ( 95 percent confidence interval , 1.86 to 2.95 ) times that in the medical-therapy group , with a predominance of infection , bleeding , and malfunction of the device . The quality of life was significantly improved at one year in the device group . CONCLUSIONS The use of a left ventricular assist device in patients with advanced heart failure result ed in a clinical ly meaningful survival benefit and an improved quality of life . A left ventricular assist device is an acceptable alternative therapy in selected patients who are not c and i date s for cardiac transplantation OBJECTIVE Newer generation left ventricular assist devices ( LVADs ) are established for long-term support . The aim of this multi-modal intervention was to improve the body weight , exercise tolerance and psychosocial status in out patients on long-term LVAD support . METHODS Seventy patients participated in this non-r and omized intervention study [ intervention group ( IGr ) n = 34 ; control group ( CGr ) n = 36 ] over 18 months ( T1-T4 ) ; the baseline sample characteristics showed no differences between groups . Dietary counselling and weight management intervention was performed by a dietician based on a specific algorithm . Physical reconditioning followed a home ergometry protocol and was supplemented by psychosocial counselling . The outcomes were measured based on the body mass index ( BMI ) , cardiopulmonary exercise testing and self-report [ hospital anxiety and depression scale ( HADS ) , SF-36 ] . RESULTS The intervention showed a strong positive effect on nutrition and weight management [ 95 % confidence interval ( CI ) : -0.71 - 0.69 ; effect size ( ES ) : 0.907 ; P = 0.02 ) ] , result ing in the normal BMI ( kg/m(2 ) ) values in the IGr ( T1 : 24.0 ± 0.6 ; T4 : 24.5 ± 1.1 ; P = 0.35 ) compared with a significant BMI increase in the CGr ( T1 : 23.8 ± 0.6 ; T4 : 29.7 ± 0.8 ; P = 0.05 ) . Significant differences appeared regarding exercise tolerance ( VO(2)max/% predicted ) in favour of IGr patients ( IGr : 69 ± 2.9 ; CGr 62 ± 3.7 ; P = 0.04 ) . This increase was reflected by patients ' self-reporting based on the SF-36 physical component score ( IGr : P = 0.04 ; CGr : P = 0.54 ) . SF-36 psychosocial component scores showed no changes for both groups . However , CGr showed a tendency for increased anxiety scores relative to their counterparts ( IGr : 4.95 ± 0.4 ; CGr : 6.6 ± 0.9 ; P = 0.03 ) . CONCLUSIONS IGr patients showed a strong benefit from a multi-modal intervention , including dietary counselling , controlled exercise and psychosocial support . Dietary counselling holds potential to prevent obesity in this patient population BACKGROUND Patients with advanced heart failure have improved survival rates and quality of life when treated with implanted pulsatile-flow left ventricular assist devices as compared with medical therapy . New continuous-flow devices are smaller and may be more durable than the pulsatile-flow devices . METHODS In this r and omized trial , we enrolled patients with advanced heart failure who were ineligible for transplantation , in a 2:1 ratio , to undergo implantation of a continuous-flow device ( 134 patients ) or the currently approved pulsatile-flow device ( 66 patients ) . The primary composite end point was , at 2 years , survival free from disabling stroke and reoperation to repair or replace the device . Secondary end points included survival , frequency of adverse events , the quality of life , and functional capacity . RESULTS Preoperative characteristics were similar in the two treatment groups , with a median age of 64 years ( range , 26 to 81 ) , a mean left ventricular ejection fraction of 17 % , and nearly 80 % of patients receiving intravenous inotropic agents . The primary composite end point was achieved in more patients with continuous-flow devices than with pulsatile-flow devices ( 62 of 134 [ 46 % ] vs. 7 of 66 [ 11 % ] ; P<0.001 ; hazard ratio , 0.38 ; 95 % confidence interval , 0.27 to 0.54 ; P<0.001 ) , and patients with continuous-flow devices had superior actuarial survival rates at 2 years ( 58 % vs. 24 % , P=0.008 ) . Adverse events and device replacements were less frequent in patients with the continuous-flow device . The quality of life and functional capacity improved significantly in both groups . CONCLUSIONS Treatment with a continuous-flow left ventricular assist device in patients with advanced heart failure significantly improved the probability of survival free from stroke and device failure at 2 years as compared with a pulsatile device . Both devices significantly improved the quality of life and functional capacity . ( Clinical Trials.gov number , NCT00121485 . OBJECTIVES This study examined the effects of a cardiac rehabilitation ( CR ) program on functional capacity and health status ( HS ) in patients with newly implanted left ventricular assist devices ( LVADs ) . BACKGROUND Reduced functional capacity and HS are independent predictors of mortality in patients with heart failure . CR improves both , and is related to improved outcomes in patients with heart failure ; however , there is a paucity of data that describe the effects of CR in patients with LVADs . METHODS Enrolled subjects ( n = 26 ; 7 women ; age 55 ± 13 years ; ejection fraction 21 ± 8 % ) completed a symptom-limited cardiopulmonary exercise test , the Kansas City Cardiomyopathy Question naire ( KCCQ ) , a 6-min walk test ( 6MW ) , and single-leg isokinetic strength test before 2:1 r and omization to CR versus usual care . Subjects in the CR group underwent 18 visits of aerobic exercise at 60 % to 80 % of heart rate reserve . Within-group changes from baseline to follow-up were analyzed with a paired t-test , whereas an independent t-test was used to determine differences in the change between groups . RESULTS Within-group improvements were observed in the CR group for peak oxygen uptake ( 10 % ) , treadmill time ( 3.1 min ) , KCCQ score ( 14.4 points ) , 6MW distance ( 52.3 m ) , and leg strength ( 17 % ) . Significant differences among groups were observed for KCCQ , leg strength , and total treadmill time . CONCLUSIONS Indicators of functional capacity and HS are improved in patients with continuous-flow LVADs who attend CR . Future trials should examine the mechanisms responsible for these improvements , and if such improvements translate into improved clinical outcomes . ( Cardiac Rehabilitation in Patients With Continuous Flow Left Ventricular Assist Devices : Rehab VAD Trial [ RehabVAD ] ; NCT01584895 ) BACKGROUND A paucity of studies has examined the effect of exercise training after left ventricular assist device ( LVAD ) implantation . Previous research has demonstrated that insertion of the LVAD alone improves exercise capacity and quality of life ( QOL ) . This study investigated whether supervised exercise training results in a further improvement . METHODS This prospect i ve , r and omized controlled trial with concealed allocation , assessor blinding , and intention-to-treat analysis investigated the effect of exercise training on exercise capacity and QOL in 14 patients who underwent LVAD insertion as a bridge to heart transplantation . Exercise training consisted of 8 weeks of gym-based aerobic and strengthening exercises 3 times a week , with a progressive mobilization program , compared with the control group that completed mobilization alone . Exercise capacity was measured before and after the intervention using maximal cardiopulmonary exercise testing and 6-minute walk distance ( 6MWD ) . QOL was measured using the Short Form 36-item assessment . RESULTS No adverse events were reported . There was a trend toward greater improvement in peak oxygen consumption ( Vo(2 ) ) , 6MWD , and QOL in the exercise group ( n = 7 ) compared with the control group ( n = 7 ) ; however , no significant between-group difference was detected for improvements in peak Vo(2 ) [ mean difference ( exercise -- control ) ] of 2.96 ml/kg/min ( 95 % confidence interval , -1.04 to 6.97 ) , 6MWD at 54 meters ( -51 to 159 meters ) , and QOL scores over time ( p > 0.05 ) . CONCLUSION Exercise training is feasible and safe in patients with a LVAD . Trends toward greater improvement in exercise capacity and QOL after exercise training warrant further investigation in a larger trial BACKGROUND The future burden of heart failure in Japan was projected to 2055 in order to prospect ively estimate of the number of these patients . METHODS AND RESULTS The statistics are based on prevalence data of left ventricular dysfunction ( LVD ) in Sado City using the Sado Heart Failure Study ( 2003 ) and population estimates from the Japanese National Institute of Population and Social Security Research Report ( 2006 ) . The number of Japanese out patients with LVD was 979,000 in 2005 , and is predicted to increase gradually as the population ages , reaching 1.3 million by 2030 . CONCLUSION LVD is expected to precipitate a future epidemic of heart failure in Japan BACKGROUND If an association between a decline in physical performance and subjective QOL is confirmed , the SPPB could be used as a predictor for declining QOL in older people . OBJECTIVE This study aim ed to eluci date the association between the short physical performance battery ( SPPB ) and QOL ( EQ-5D ) to determine the utility of the SPPB as a predictor of declining QOL . METHODS The SPPB and the EQ-5D test were performed with a r and om sample of participants nested in the Korean Longitudinal Study of Aging ( KLoSA ) panel . Comparisons of the adjusted mean scores on the EQ-5D index between normal and abnormal SPPB groups were performed . We selected the quartiles of the EQ-5D index variables for the analysis . The association between the EQ-5D index and SPPB abnormality was examined using multinomial logistic regression analysis . Additionally , the associations between gait speed and chair st and time and the EQ-5D index were examined using the same analysis . RESULTS Four hundred and twenty-two subjects were included in the analysis . The adjusted means for the EQ-5D index were significantly lower when the SPPB score was abnormal ( p=0.022 for men , p=0.047 for women ) . An abnormal SPPB score was significantly associated with the lowest quartile of EQ-5D index score ( adjusted OR 3.54 in the lowest quartile for men ; adjusted OR 2.50 and 3.37 in the lowest and second quartiles for women ) . Gait speed was significantly associated with the EQ-5D index for participants of both sexes , but st and up time was associated with the EQ-5D index only for men . CONCLUSIONS An abnormal SPPB score was associated with lower QOL . Thus , the SPPB has the potential to be used as an early predictor of declining QOL in clinical setting s and epidemiological studies |
12,472 | 19,160,336 | There was no difference in mortality , liver failure , or other morbidities .
The blood loss was significantly lower in vascular occlusion compared with no vascular occlusion .
Intermittent vascular occlusion seems safe in liver resection .
However , it does not seem to decrease morbidity . | BACKGROUND Vascular occlusion is used to reduce blood loss during liver resection .
There is considerable controversy regarding whether vascular occlusion should be used or not during elective liver resections .
OBJECTIVES To assess the advantages ( decreased blood loss and peri-operative morbidity ) and disadvantages ( ischaemia-reperfusion injury related complications like liver dysfunction ) of vascular occlusion during elective liver resections . | AIM To investigate the effect of low central venous pressure ( LCVP ) on blood loss during hepatectomy for hepatocellular carcinoma ( HCC ) . METHODS By the method of sealed envelope , 50 HCC patients were r and omized into LCVP group ( n=25 ) and control group ( n=25 ) . In LCVP group , CVP was maintained at 2 - 4 mmHg and systolic blood pressure ( SBP ) above 90 mmHg by manipulation of the patient 's posture and administration of drugs during hepatectomy , while in control group hepatectomy was performed routinely without lowering CVP . The patients ' preoperative conditions , volume of blood loss during hepatectomy , volume of blood transfusion , length of hospital stay , changes in hepatic and renal functions were compared between the two groups . RESULTS There were no significant differences in patients ' preoperative conditions , maximal tumor dimension , pattern of hepatectomy , duration of vascular occlusion , operation time , weight of resected liver tissues , incidence of post-operative complications , hepatic and renal functions between the two groups . LCVP group had a markedly lower volume of total intraoperative blood loss and blood loss during hepatectomy than the control group , being 903.9+/-180.8 mL vs 2 329.4+/-2 538.4 ( W=495.5 , P<0.01 ) and 672.4+/-429.9 mL vs 1 662.6+/-1 932.1 ( W=543.5 , P<0.01 ) . There were no remarkable differences in the pre-resection and post-resection blood losses between the two groups . The length of hospital stay was significantly shortened in LCVP group as compared with the control group , being 16.3+/-6.8 d vs 21.5+/-8.6 d ( W=532.5 , P<0.05 ) . CONCLUSION LCVP is easily achievable in technique . Maintenance of CVP < or= 4 mmHg can help reduce blood loss during hepatectomy , shorten the length of hospital stay , and has no detrimental effects on hepatic or renal function Objective This prospect i ve r and omized study determined the influence of closed-suction drainage on the incidence of postoperative complications after elective hepatic resection . Summary Background Data Routine drainage is no longer advocated after several intra-abdominal surgical procedures . Methods A series of 81 patients who underwent elective hepatic resection were r and omly allocated to either a nondrainage group ( n = 39 ) and a drainage group with closed-suction drainage ( n = 42 ) . Indications for resection were 42 benign lesions and 39 malignant tumors , including 19 with cirrhosis . Major hepatic resection was performed in 25 patients and minor resection , in 56 . All patients underwent ultrasonography with puncture for bacteriologic cultures of all fluid collection s within the first 5 postoperative days . Results One patient died in each group . Ultrasonography found a significantly higher rate of subphrenic collection s in the drainage group compared with the nondrainage group ( respectively , 36 % vs. 15 % , p < 0.05 ) . These collection s were more frequently infected in the drainage group ( n = 6 ) than in the nondrainage group ( n = 2 ) . After major liver resection , the rate of intra-abdominal postoperative complications ( i.e. , subphrenic fluid collection s , hematomas , and bilomas ) was similar between the two groups . Conclusion Minor liver resection is safer without drainage . Major liver resection can be performed with or without abdominal drainage BACKGROUND Two r and omized prospect i ve studies suggested that ischemic preconditioning ( IP ) protects the human liver against ischemia-reperfusion injury after hepatectomy performed under continuous clamping of the portal triad . The primary goal of this study was to determine whether IP protects the human liver against ischemia-reperfusion injury after hepatectomy under continuous vascular exclusion with preservation of the caval flow . STUDY DESIGN Sixty patients were r and omly divided into two groups : with ( n=30 ; preconditioning group ) and without ( n=30 ; control group ) IP ( 10 minutes of portal triad clamping and 10 minutes of reperfusion ) before major hepatectomy under vascular exclusion of the liver preserving the caval flow . Serum concentrations of aspartate transferase , alanine transferase , glutathione-S-transferase , and bilirubin and prothrombin time were regularly determined until discharge and at 1 month . Morbidity and mortality were determined in both groups . RESULTS Peak postoperative concentrations of aspartate transferase were similar in the groups with and without IP ( 851 + /- 1,733 IU/L and 427 + /- 166 IU/L respectively , p=0.2 ) . A similar trend toward a higher peak concentration of alanine transferase and glutathione-S-transferase was indeed observed in the preconditioning group compared with the control group . Morbidity and mortality rates and lengths of ICU and hospitalization stays were similar in both groups . CONCLUSIONS IP does not improve liver tolerance to ischemia-reperfusion after hepatectomy under vascular exclusion of the liver with preservation of the caval flow . This maneuver does not improve postoperative liver function and does not affect morbidity or mortality rates . The clinical use of IP through 10 minutes of warm ischemia in this technique of hepatectomy is not currently recommended OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Background / Aims : Degradation of adenine nucleotides to adenosine has been suggested to play a critical role in ischemic preconditioning ( IPC ) . Thus , we question ed in patients undergoing partial hepatectomy whether ( i ) IPC will increase plasma purine catabolites and whether ( ii ) formation of purines in response to vascular clamping ( Pringle maneuver ) can be attenuated by prior IPC . Methods : 75 patients were r and omly assigned to three groups : group I underwent hepatectomy without vascular clamping ; group II was subjected to the Pringle maneuver during resection , and group III was preconditioned ( 10 min ischemia and 10 min reperfusion ) prior to the Pringle maneuver for resection . Central , portal venous and arterial plasma concentrations of adenosine , inosine , hypoxanthine and xanthine were determined by high-performance liquid chromatography . Results : Duration of the Pringle maneuver did not differ between patients with or without IPC . Surgery without vascular clamping had only a minor effect on plasma purine concentrations . After IPC , plasma concentrations of purines transiently increased . After the Pringle maneuver alone , purine plasma concentrations were most increased . This strong rise in plasma purines caused by the Pringle maneuver , however , was significantly attenuated by IPC . When portal venous minus arterial concentration difference was calculated for inosine or hypoxanthine , the respective differences became positive in patients subjected to the Pringle maneuver and were completely prevented by preconditioning . Conclusion : These data demonstrate that ( i ) IPC increases formation of adenosine , and that ( ii ) the unwanted degradation of adenine nucleotides to purines caused by the Pringle maneuver can be attenuated by IPC . Because IPC also induces a decrease of portal venous minus arterial purine plasma concentration differences , IPC might possibly decrease disturbances in the energy metabolism in the intestine as well Objective : To st and ardize the definition of postoperative liver failure ( PLF ) for prediction of early mortality after hepatectomy . Summary Background Data : The definition of PLF is not st and ardized , making the comparison of innovations in surgical techniques and the timely use of specific therapeutic interventions complex . Methods : Between 1998 and 2002 , 775 elective liver resections , including 69 % for malignancies and 60 % major resections , were included in a prospect i ve data base . The nontumorous liver was abnormal in 43 % with steatosis > 30 % in 14 % , noncirrhotic fibrosis in 43 % , and cirrhosis in 12 % . The impact of prothrombin time ( PT ) < 50 % and serum bilirubin ( SB ) > 50 & mgr;mol/L on postoperative days ( POD ) 1 , 3 , 5 , and 7 was analyzed . Results : The lowest PT level was observed on postoperative day ( POD ) 1 , while the peak of SB was observed on POD 3 . These 2 variables tended to return to preoperative values by POD 5 . The median interval between hepatectomy and postoperative death was 15 days ( range , 5–39 days ) . Postoperative mortality significantly increased in patients with PT < 50 % and SB > 50 & mgr;ml/L. The conjunction of PT < 50 % and SB > 50 & mgr;mol/L on POD 5 was a strong predictive factor of mortality . In patients with significant morbidity , this “ 50 - 50 criteria ” was met 3 to 8 days before clinical evidence of complications . Conclusions : The association of PT < 50 % and SB > 50 & mgr;ml/L on POD 5 ( the 50 - 50 criteria ) was a simple , early , and accurate predictor of more than 50 % mortality rate after hepatectomy . This criteria could be identified early enough , before clinical evidence of complications , for specific interventions to be applied in due time BACKGROUND The Pringle manoeuvre and ischaemic preconditioning are applied to prevent blood loss and ischaemia-reperfusion injury , respectively , during liver surgery . In this prospect i ve clinical trial we report on the intraoperative haemodynamic effects of the Pringle manoeuvre alone or in combination with ischaemic preconditioning . METHODS Patients ( n=68 ) were assigned r and omly to three groups : ( i ) resection with the Pringle manoeuvre ; ( ii ) with ischaemic preconditioning before the Pringle manoeuvre for resection ; ( iii ) without pedicle clamping . RESULTS Following the Pringle manoeuvre the mean arterial pressure increased transiently , but significantly decreased after unclamping as a result of peripheral vasodilation . Ischaemic preconditioning improved cardiovascular stability by lowering the need for catecholamines after liver reperfusion without affecting the blood sparing benefits of the Pringle manoeuvre . In addition , ischaemic preconditioning protected against reperfusion-induced tissue injury . CONCLUSIONS Ischaemic preconditioning provides both better intraoperative haemodynamic stability and anti-ischaemic effects thereby allowing us to take full advantage of blood loss reduction by the Pringle manoeuvre HYPOTHESIS Blood loss in hepatic resection is an important determinant of operative outcome . OBJECTIVE To clarify whether reducing the tidal volume would be effective in decreasing blood loss during liver transection . DESIGN R and omized controlled trial . SETTING University hospital . PATIENTS Eighty patients scheduled to undergo hepatic resection were r and omly assigned to receive liver transection under normoventilation ( n = 40 ) or hypoventilation ( n = 40 ) . INTERVENTIONS During liver transection , in the normoventilation group , the tidal volume was 10 mL/kg and the respiratory rate was 10/min ; in the hypoventilation group , the tidal volume was reduced to 4 mL/kg and respiratory rate was increased to 15/min . Liver transection was performed under total or selective inflow occlusion . MAIN OUTCOME MEASURE Blood loss . RESULTS Between the normoventilation and hypoventilation groups , no significant difference was found in total blood loss ( median [ range ] : 630 mL [ 72 - 3600 mL ] vs 630 mL [ 120 - 3520 mL ] ; P = .44 ) or blood loss per transection area ( median [ range ] : 7.3 mL/cm(2 ) [ 1.2 - 55.4 mL/cm(2 ) ] vs 9.8 mL/cm(2 ) [ 0.9 - 79.9 mL/cm(2 ) ] ; P = .55 ) . During liver transection , the central venous pressure was significantly reduced in the hypoventilation group than in the normoventilation group ( median [ range ] : -0.7 cm H(2)O [ -3.0 to 1.8 cm H(2)O ] vs -0.2 cm H(2)O [ -4.0 to 2.0 cm H(2)O ] ; P = .007 ) . The maximum end-tidal carbon dioxide level in the hypoventilation group was significantly higher than that in the normoventilation group ( maximum [ range ] : 50 mm Hg [ 28 - 66 mm Hg ] vs 37 mm Hg [ 27 - 60 mm Hg ] ; P<.001 ) . Transection time , postoperative liver function , hospitalization length , morbidity , and mortality were similar in the 2 groups . CONCLUSION This r and omized trial suggested no beneficial effect of reduction of tidal volume on bleeding during hepatic resection OBJECTIVE To evaluate whether vascular inflow occlusion by the Pringle maneuver during hepatectomy can be safe and effective in reducing blood loss . SUMMARY BACKGROUND DATA Hepatectomy can be performed with a low mortality rate , but massive hemorrhage during surgery remains a potentially lethal problem . The Pringle maneuver is traditionally used during hepatectomy to reduce blood loss , but there is a potential harmful effect on the metabolic function of hepatocytes . There has been no prospect i ve r and omized study to determine whether the Pringle maneuver can decrease blood loss during hepatectomy , improve outcome , or affect the metabolism of hepatocytes . METHODS From July 1995 to February 1997 , we studied 100 consecutive patients who underwent hepatectomy for liver tumors . The patients were r and omly assigned to liver transection under intermittent Pringle maneuver of 20 minutes and a 5-minute clamp-free interval ( n = 50 ) , or liver transection without the Pringle maneuver ( n = 50 ) . The surface area of liver transection was measured and blood loss during transection per square centimeter of transection area was calculated . Routine liver biochemistry , arterial ketone body ratio ( AKBR ) , and the indocyanine green ( ICG ) clearance test were done . RESULTS The two groups were comparable in terms of preoperative liver function and in the proportion of patients having major hepatectomy . The Pringle maneuver result ed in less blood loss per square centimeter of transection area ( 12 mL/cm2 vs. 22 mL/cm2 , p = 0.0001 ) , a shorter transection time per square centimeter of transection area ( 2 min/cm2 vs. 2.8 min/cm2 , p = 0.016 ) , a significantly higher AKBR in the first 2 hours after hepatectomy , lower serum bilirubin levels in the early postoperative period , and , in cirrhotic patients , higher serum transferrin levels on postoperative days 1 and 8 . The complication rate , the hospital mortality rate , and the ICG retention at 15 minutes on postoperative day 8 were equal for the two groups . CONCLUSION Performing the Pringle maneuver during liver transection result ed in less blood loss and better preservation of liver function in the early postoperative period . This is probably because there was less hemodynamic disturbance induced by the bleeding OBJECTIVE The authors compared the intra- and postoperative course of patients undergoing liver resections under continuous pedicular clamping ( CPC ) or intermittent pedicular clamping ( IPC ) . SUMMARY BACKGROUND DATA Reduced blood loss during liver resection is achieved by pedicular clamping . There is controversy about the benefits of IPC over CPC in humans in terms of hepatocellular injury and blood loss control in normal and abnormal liver parenchyma . METHODS Eighty-six patients undergoing liver resections were included in a prospect i ve r and omized study comparing the intra- and postoperative course under CPC ( n = 42 ) or IPC ( n = 44 ) with periods of 15 minutes of clamping and 5 minutes of unclamping . The data were further analyzed according to the presence ( steatosis > 20 % and chronic liver disease ) or absence of abnormal liver parenchyma . RESULTS The two groups of patients were similar in terms of age , sex , nature of the liver tumors , results of preoperative assessment , proportion of patients undergoing major or minor hepatectomy , and nature of nontumorous liver parenchyma . Intraoperative blood loss during liver transsection was significantly higher in the IPC group . In the CPC group , postoperative liver enzymes and serum bilirubin levels were significantly higher in the subgroup of patients with abnormal liver parenchyma . Major postoperative deterioration of liver function occurred in four patients with abnormal liver parenchyma , with two postoperative deaths . All of them were in the CPC group . CONCLUSIONS This clinical controlled study clearly demonstrated the better parenchymal tolerance to IPC over CPC , especially in patients with abnormal liver parenchyma Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . BACKGROUND Intermittent Pringle manoeuvre result ed in less blood loss and better preservation of liver function when it was applied for fewer than 120 minutes . The mechanism of better preservation of liver function under intermittent Pringle manoeuvre at molecular level remains unclear . Furthermore , the ultrastructural features in the liver with chronic diseases under intermittent Pringle manoeuvre have not been studied . The aim of the study is to investigate the expression of stress genes and ultrastructural change of the liver under intermittent Pringle manoeuvre . METHODS From July 1995 to February 1998 , 131 patients underwent hepatectomy for liver tumours ( 61 patients without Pringle manoeuvre and 70 patients with intermittent Pringle manoeuvre ) . Twenty-five patients ( 15 with Pringle manoeuvre and 10 without Pringle manoeuvre ) were included in the study of hepatic stress gene expression during hepatectomy . Twenty-two patients ( 18 patients with intermittent Pringle manoeuvre and four patients without Pringle manoeuvre ) were r and omly assigned for electron microscopic examination . RESULTS For the expression of stress genes , both the heat shock genes ( HSP 70A and HSC 70 ) and acute phase genes ( TNF-alpha and interleukin-6 ) were detected simultaneously in the patients with or without intermittent Pringle manoeuvre . The patients under intermittent Pringle manoeuvre had relatively higher mRNA levels of heat shock gene 70 family , which is related to intracellular repair and protection . Induction of TNF-alpha and interleukin-6 genes , which contributed to ischaemia-reperfusion injury and postoperative complication , was not found in the patients under intermittent Pringle manoeuvre . Under the electron microscopy , the hepatic ultrastructure was well maintained under intermittent Pringle manoeuvre whatever the liver status , even when the accumulated ischaemic duration was extended to 120 min . CONCLUSION Intermittent Pringle manoeuvre induced relatively higher expression of heat shock genes , which are related to intracellular homeostasis , and is consistent with the well maintenance of liver ultrastructure OBJECTIVE The authors compared operative course of patients undergoing major liver resections under portal triad clamping ( PTC ) or under hepatic vascular exclusion ( HVE ) . SUMMARY BACKGROUND DATA Reduced blood loss during liver resection is achieved by PTC or HVE . Specific complications and postoperative hepatocellular injury mediated with two procedures have not been compared . METHODS Fifty-two noncirrhotic patients undergoing major liver resections were included in a prospect i ve r and omized study comparing both the intraoperative and postoperative courses under PTC ( n = 24 ) or under HVE ( n = 28 ) . RESULTS The two groups were similar at entry , but eight patients were crossed over to the other group during resection . In the HVE group , hemodynamic intolerance occurred in four ( 14 % ) patients . In the PTC group , pedicular clamping was not efficient in four patients , including three with involvement of the cavohepatic intersection and one with persistent bleeding due to tricuspid insufficiency . Intraoperative blood losses and postoperative enzyme level reflecting hepatocellular injury were similar in the two groups . Mean operative duration and mean clampage duration were significantly increased after HVE . Postoperative abdominal collection s and pulmonary complications were 2.5-fold higher after HVE but without statistical significance , whereas the mean length of postoperative hospital stay was longer after HVE . CONCLUSIONS This study shows that both methods of vascular occlusion are equally effective in reducing blood loss in major liver resections . The HVE is associated with unpredictable hemodynamic intolerance , increased postoperative complications with a longer hospital stay , and should be restricted to lesions involving the cavo-hepatic intersection HYPOTHESES Temporary vascular clampage ( Pringle maneuver ) during liver surgery can cause ischemia-reperfusion injury . In this process , activation of polymorphonuclear leukocytes ( PMNLs ) might play a major role . Thus , we investigated the effects of hepatic ischemic preconditioning on PMNL functions . DESIGN Prospect i ve r and omized study . Patients who underwent partial liver resection were r and omly assigned to 3 groups : group 1 without Pringle maneuver ; group 2 with Pringle maneuver , and group 3 with ischemic preconditioning using 10 minutes of ischemia and 10 minutes of reperfusion prior to Pringle maneuver for resection . SETTING University hospital , Munich , Germany . PATIENTS Seventy-five patients underwent hepatic surgery mostly owing to metastasis . MAIN OUTCOME MEASURES Perioperative factors for PMNL activation , inflammation , and postoperative hepatocellular integrity . RESULTS Ischemia-reperfusion of the human liver ( mean + /- SD time to perform the Pringle maneuver , 35.5 + /- 2.6 minutes ) caused ( 1 ) a decrease in the number of circulating PMNLs , ( 2 ) their intrahepatic sequestration , ( 3 ) their systemic activation , and ( 4 ) a significant correlation between the degree of their postischemic activation and the postoperative rise in liver enzyme serum levels . In parallel , cytokines with proinflammatory and chemotactic properties were released reaching the highest values when stimulation of PMNLs was most pronounced . When ischemic preconditioning preceded the Pringle maneuver , activation of PMNLs and cytokine plasma levels was reduced as evidence d by the attenuation of superoxide anion production , beta(2)-integrin up-regulation , and interleukin 8 serum concentrations , followed by a significant reduction in serum alanine aminotransferase levels on the first and second postoperative days . CONCLUSIONS These results demonstrate in humans that ischemic preconditioning reduces activation of PMNLs elicited by the Pringle maneuver . The down-regulation of potentially cytotoxic functions of PMNLs might be one of yet unknown important pathways that altogether mediate protection by ischemic preconditioning The intermittent Pringle manoeuvre during hepatectomy results in a better clinical outcome when the accumulated ischaemia time is less than 120 min . The aim of this study was to investigate hepatic gene expression related to microcirculatory modulation and ultrastructural changes in patients having the intermittent Pringle manoeuvre Animal studies suggest that acute phase reactant cytokines and polymorphonuclear leukocytes ( PMN ) may play a critical role in ischemia‐ reperfusion injury . To evaluate whether similar mechanisms are operative in human liver , six cirrhotic and nine noncirrhotic patients undergoing right hepatectomy were r and omized for utilization of hepatic vascular exclusion ( HVE ) as a model of ischemia‐reperfusion injury . Portal and systemic levels of acute reactant cytokines ( interleukin 6 [ IL‐6 ] , interleukin 1 [ IL‐1 ] , tumor necrosis factor α [ TNF‐α ] ) and neutrophil adhesion in serial liver biopsy specimens were studied . Correlations among mediators , leukocyte adhesion , and markers of liver injury were also evaluated . Hepatic vascular exclusion result ed in substantial and reproducible changes in portal and arterial IL‐6 levels in both cirrhotic and noncirrhotic patients . Portal and systemic cytokine levels were comparable in most instances , whereas levels were usually higher in cirrhotic patients than in noncirrhotic patients . Negative correlations were found between IL‐6 levels at the time of reperfusion and later TNF‐α levels . IL‐6 levels correlated negatively with numerous markers of hepatocellular injury and the number of postoperative complications . Hepatic vascular exclusion increased neutrophils adhesion after reperfusion in cirrhotic patients but not in noncirrhotic patients . In cirrhotic patients , the degree of leukocyte adhesion after reperfusion correlated with several postoperative markers of liver injury . This study in humans shows that acute reactant cytokines are released during liver ischemia and , interestingly , that IL‐6 levels strongly correlate with clinical and laboratory measures of injury . Further studies to evaluate possible causal relationship with hepatic injury are warranted , with emphasis on the role of IL‐6 and PMN adhesion |
12,473 | 23,452,972 | Based on the literature , there is a lack of reliable evidence to support the effectiveness of remineralizing agents for the treatment of postorthodontic white spot lesions | INTRODUCTION White spot lesions are a common complication after orthodontic treatment .
The aim of this systematic review was to investigate which remineralizing agents are effective for the treatment of white spot lesions after orthodontic treatment . | INTRODUCTION This article illustrates a new treatment method and evaluates the effect of the frequent use of fluori date d chewing sticks ( miswaks ) on the remineralization of white spot lesions ( WSLs ) diagnosed at debonding . METHODS Thirty-seven orthodontic patients ( mean age , 17.2 years ) , with a minimum of 4 WSLs on the buccal surfaces of the maxillary incisors , canines , premolars , and first molars after orthodontic therapy , were enrolled in a double-blind , r and omized , longitudinal trial lasting 6 weeks . The subjects were divided into 2 groups using fluori date d miswaks impregnated in 0.5 % sodium fluoride ( test group , n = 19 ) and nonfluori date d miswaks ( control group , n = 18 ) . A custom-made mouth tray , covering half of the maxillary dentition , was used while brushing with the miswaks 5 times per day . The WSLs were scored by using a DIAGNOdent pen ( KaVo , Biberach , Germany ) and with the International Caries Detection and Assessment System ( ICDAS II ) index , at baseline and 2 , 4 , and 6 weeks after debonding . RESULTS Both the DIAGNOdent readings and the ICDAS II index of the WSLs decreased in the test group on the uncovered side of the dentition but not on the covered side during the 6-week trial ( P < 0.0001 ) . There was also a slight improvement in the control group ( not significant ) . There was a strong correlation between the DIAGNOdent values and the ICDAS II index when all the data were pooled ( P < 0.001 ) . CONCLUSIONS The frequent use of fluori date d miswaks had a remineralizing effect on WSLs . The DIAGNOdent pen might be a useful tool for diagnosing and monitoring changes of WSLs over a relatively short period of time Orthodontic treatment with fixed appliances is considered a risk factor for the development of white spot caries lesions ( WSL ) . Traditionally , brackets are bonded to the buccal surfaces . Lingual brackets are developing rapidly and have become more readily available . Buccal surfaces are considered to be more caries prone than lingual surfaces . Furthermore , lingual brackets are shaped to fit the morphology of the teeth and seal almost the entire surface . In the present study we tested the hypothesis that lingual brackets result in a lower caries incidence than buccal brackets . We tested this hypothesis using a split-mouth design where subjects were allocated r and omly to a group receiving either buccal or lingual brackets on the maxillary teeth and the alternative bracket type in the m and ible . The results indicate that buccal surfaces are more prone to WSL development , especially when WSL existed before treatment . The number of WSL that developed or progressed on buccal surfaces was 4.8 times higher than the number of WSL that developed or progressed on lingual surfaces . When measured using quantitative light-induced fluorescence ( QLF ) , the increase in integrated fluorescence loss was 10.6 times higher buccally than lingually . We conclude that lingual brackets make a difference when caries lesion incidence is concerned Dental caries and result ing tooth decay can produce a multifactorial destructive process with a very high incidence . Cariogenic bacteria attack enamel with acids that produce subsurface lesions , thereby weakening the enamel and allowing bacterial progression into the dentin . The formation of dental decay , because of demineralization of the tooth structure , can be prevented or delayed by increasing the rate of the tooth 's remineralization and replacement relative to the tooth 's rate of demineralization . This rebuilding of enamel may be accelerated by the addition of amorphous calcium phosphate ( ACP ) with the aid of casein phosphopeptide ( CPP ) ( Recaldent molecule ) . In this study , the role of CPP in stabilizing and releasing ACP on the tooth surface has been investigated to better underst and its efficacy in the prevention of tooth demineralization in orthodontic patients . Twenty-five patients who wore fixed orthodontic appliances were enrolled in this clinical trial . It was explained to the patients that CPP-ACP would be used for 3 weeks and then suspended for an additional 3 weeks . Salivary pH evaluation , plaque pH evaluation and oral hygiene index ( OHI ) were performed at T0 , T1 and T2 . Results showed an increase in OHI level and an increase of the salivary pH ( 76 % of the patients ) . Instead of plaque pH level that showed trivial results , only 48 % of the patients showed a bacterial plaque pH increase . In conclusion , this study has not provided unequivocal evidence for the protective properties of Recaldent molecule . Long-term studies are necessary to better underst and the role of this molecule INTRODUCTION Enamel demineralization is a problem in orthodontics . Fluoride is partially effective in addressing this problem , but additional treatment options are needed . The objective of this prospect i ve r and omized controlled trial was to determine the effectiveness of a new product , MI Paste Plus ( GC America , Alsip , Ill ) , in the prevention or reduction of white spot lesions in orthodontic patients . METHODS Sixty patients who were undergoing routine orthodontic treatment were recruited for this prospect i ve r and omized clinical trial . A double-blind method of r and omization was used to determine whether each patient received the MI Paste Plus or a placebo paste ( Tom 's of Maine , Salisbury , United Kingdom ) . Each patient was asked to administer the paste by using a fluoride tray for a minimum of 3 to 5 minutes each day at night after brushing . Photographic records obtained in a light-controlled environment were used to record the presence or absence of white spot lesions in both groups . The enamel decalcification index was used to determine the number of white spot lesions per surface at each time interval . Patients were followed at 4-week intervals for 3 months . A scoring system from 0 to 6 was used to determine the level of caries or cavitations . This system was also used for each tooth at each time interval . RESULTS Fifty patients ( 26 using MI Paste Plus , 24 using the placebo paste ) completed the study . The enamel decalcification index scores for all surfaces were 271 and 135 at the start of treatment and 126 and 258 at the end of treatment for the MI Paste Plus and placebo paste groups , respectively . The enamel decalcification index scores in the MI Paste Plus group reduced by 53.5 % , whereas the placebo group increased by 91.1 % during the study period . A 3-way analysis of variance ( ANOVA ) was done for the average enamel decalcification index scores . The surface type , the product/time interactions , and the product/surface interactions of the mean enamel decalcification index scores were significant ( P < 0.05 ) . CONCLUSIONS MI Paste Plus helped prevent the development of new white spot lesions during orthodontic treatment and decreased the number of white spot lesions already present . The placebo paste had no preventive action on white spot development during orthodontic treatment ; the number of lesions actually increased . MI Paste Plus reduced white spots on the gingival surfaces ; the placebo paste had the opposite effect . The incisal surface effect on the mean enamel decalcification index scores over time and between products was highly significant . The incisal enamel decalcification index scores were consistently higher than those for the other surfaces ( mesial , distal , and gingival ) The aims of this in vitro study were 2‐fold : 1 ) to evaluate two fluorescence methods ( DIAGNOdent and QLF ( quantitative light‐induced fluorescence ) ) for quantification of white spot lesions adjacent to fixed orthodontic appliances ; and 2 ) to determine the inter‐observer agreement of the DIAGNOdent and QLF methods for quantification of incipient enamel lesions adjacent to fixed orthodontic appliances . Forty‐one premolar teeth with visually sound smooth surfaces or visually white spot enamel lesions were included in the study . Orthodontic brackets were fixed adjacent to the lesions , thus simulating the position of fixed appliances during orthodontic treatment . All teeth were measured using both the DIAGNOdent and QLF methods . Of the 41 teeth , 20 smooth surfaces were r and omly selected and analyzed by 4 operators using both DIAGNOdent and QLF . The teeth were sectioned into 300‐μm‐thick slices using a water‐cooled diamond saw and the slices manually ground to 80–100 μm thickness . Histopathology and transverse microradiography were performed to provide the gold st and ards for verification of lesion depth and mineral loss , respectively . The Spearman rank correlation coefficients between lesion depth determined by histopathology and the DIAGNOdent and QLF were 0.76 and 0.82 , respectively , whereas the Pearson correlation coefficients between mineral loss and the two methods were 0.64 and 0.84 , respectively . Inter‐observer agreement was found to be 0.80 and 0.93 for DIAGNOdent and QLF , respectively . In conclusion , QLF may be a suitable method for quantifying incipient carious lesions adjacent to fixed orthodontic appliances This study investigated , using digital bitewing radiography , the progression and regression of approximal caries in adolescent subjects chewing a sugar-free gum containing 54 mg CPP-ACP relative to the identical gum without CPP-ACP . 2,720 subjects from 29 schools were r and omly assigned to one of the two gums and were instructed to chew their assigned gum for 3 × 10 min/day , with one session supervised on school days , over the 24-month study period . St and ardized digital bitewing radiographs were taken at the baseline and 24-month clinical examinations for each subject . The radiographs , scored by a single examiner , were assessed for approximal surface dental caries at both the enamel and dentine level . Surface level transitions were scored using a transition matrix . Caries progression or regression was analysed using proportional-odds ordered logistic regression modelling of the transition scores at the tooth surface level . There was a statistically significant difference in the frequency distributions of the transition scores between the two gum groups ( OR = 0.82 , p = 0.03 ) . For subjects chewing the CPP-ACP gum the odds of a surface experiencing caries progression were 18 % less than those of a surface experiencing caries progression for subjects chewing the control gum . In conclusion , the 54 mg CPP-ACP sugar-free gum significantly slowed progression and enhanced regression of approximal caries relative to a control sugar-free gum in a 24-month clinical trial BACKGROUND Remineralization process is accelerated by the presence of fluoride ions in the oral environment , but this mechanism of caries reversal will be further enhanced if the concentration of calcium , phosphate and fluoride ions is supersaturated with respect to that of oral fluids . AIM This in vivo study was carried out to evaluate and compare the remineralizing efficacy of a urea-based mineral-enriched mouthrinse and a fluori date d dentifrice using an in vivo intraoral appliance model and polarized light microscopic evaluation technique . MATERIAL S AND METHODS The specimens were prepared from sound teeth and artificial caries was produced using an artificial caries medium in vitro and enamel specimens were inserted in removable orthodontic appliances that were to be worn by 14 children of 10 - 15 years of age . They were divided into three groups - nonfluori date d dentifrice , fluori date d dentifrice and mineral-enriched mouthrinse groups . After the 6-month experimental period , during which the enamel specimens inserted in the intraoral appliance were subjected to one of the agents ( either fluoride , nonfluoride dentifrice or mouthrinse ) in vivo , the specimens were retrieved from the patients and were evaluated using the polarized light microscopic technique . OBSERVATIONS AND RESULTS On analysis , mineral gain occurred in all groups , viz . nonfluoride dentifrice group , fluoride dentifrice and mineral-enriched mouthrinse group . However , it was found to be complete in the mouthrinse group , i.e. both at the surface and at the subsurface ( 67 % ) , while in the fluori date d dentifrice group , 43 % of the sample s showed mineral gain in both zones . In the nonfluori date d dentifrice group also , remineralization occurred but was limited either to the surface or the subsurface zone . CONCLUSIONS Urea-based mineral-enriched mouthrinse was shown to be more efficacious in the process of remineralization of artificial carious lesions BACKGROUND The anticariogenic potential of casein phosphopeptide-amorphous calcium phosphate nanocomplexes ( CPP-ACP ) has been demonstrated using laboratory , animal and human in situ caries models . The aim of this study was to determine the effect of CPP-ACP incorporation into a sugar-free lozenge ( pressed mint tablet ) on enamel remineralization in a human in situ model . METHODS The study utilized a double-blind , r and omized , cross-over design with four treatments : ( i ) a lozenge containing 56.4 mg ( 3 per cent w/w ) CPP-ACP ; ( ii ) a lozenge containing 18.8 mg ( 1 per cent w/w ) CPP-ACP ; ( iii ) a lozenge not containing CPP-ACP ; and ( iv ) a no lozenge nil-treatment control . Ten subjects wore removable palatal appliances with four , human-enamel , half-slab insets containing subsurface lesions . Lozenges were consumed , without chewing , four times per day for 14 days duration . After each treatment period the enamel slabs were removed , paired with their respective demineralized control , embedded , sectioned and subjected to microradiography and computer-assisted densitometric image analysis to determine the level of remineralization . RESULTS The incorporation of CPP-ACP into the lozenge significantly increased enamel subsurface lesion remineralization with 18.8 and 56.4 mg of CPP-ACP increasing remineralization by 78 and 176 per cent respectively , relative to the control sugarfree lozenge . CONCLUSION This study demonstrates that lozenges are a suitable vehicle for the delivery of CPP-ACP to promote enamel remineralization PURPOSE To investigate and compare the effects of a dental cream containing complexes of casein phosphoprotein-amorphous calcium phosphate ( CPP-ACP ) and fluoride mouthwashes on the regression of white spot lesions ( WSL ) . MATERIAL S AND METHODS The study group consisted of 26 healthy adolescents ( mean age 14.6 years ) exhibiting 60 teeth with 152 visible WSL sites on incisors and canines immediately after debonding of fixed orthodontic appliances . After bracket removal , professional tooth cleaning and drying , a visual scoring ( 0 - 4 ) and laser fluorescence ( LF ) readings were carried out . The patients were r and omly assigned to two different treatment protocol s with the aim of remineralising the lesions : A ) daily topical applications of a dental cream containing CPP-ACP ( Topacal ) for 3 months followed by a 3-month period of daily toothbrushing with fluori date d dentifrice , or B ) daily 0.05 % sodium fluoride mouthwash combined with fluori date d dentifrice for 6 months . The registration s were repeated after 1 , 3 , 6 and 12 months and follow-up data were compared with baseline with aid of chi-square and paired t-tests . RESULTS A significant improvement of the clinical WSL-scores was found over time in both groups , but there was a statistically significant difference ( p < 0.01 ) concerning the number of sites that totally disappeared after 12 months in favour of the CPP-ACP regime , 63 % compared with 25 % respectively . The clinical registration s were mirrored by a statistically significant decrease ( p < 0.05 ) in the LF readings at the 6- and 12-month follow-ups compared with baseline . No significant differences were displayed between the groups . CONCLUSIONS Clinical scoring and LF assessment suggested that both regimens could promote regression of WSL after debonding of fixed orthodontic appliances . The visual evaluation suggested an aesthetically more favourable outcome of the amorphous calcium phosphate treatments OBJECTIVE To evaluate the efficacy of Tooth Mousse in reducing enamel demineralization lesions adjacent to bonded orthodontic brackets and promoting remineralization in vitro . METHODS 60 bovine teeth with bonded orthodontic brackets were r and omly divided into three groups , negative control group , positive control group and experimental group , applied separately with distilled water , Duraphat fluoride varnish , Tooth Mousse . 3 groups were dipped into an artificial caries solution and an artificial saliva solution , cycling between them . All sample s were detected by polarized light microscope , scanning electron microscope and electron probe micro- analysis . RESULTS Polarized light microscope showed that the enamel surface of the experimental group were completed , the areas of positive birefringence were decreased obviously . Scanning electron microscope showed that a large number of deposits were found on the dental enamel surface of the experimental group , filled in the small local concave of enamel surface . Compared with the control group , electron probe micro- analysis showed that calcium and phosphate concentration of enamel surface was higher in experimental group than in negative control group ( P<0.05 ) , there was no significant differences between experimental group and positive control group ( P>0.05 ) . CONCLUSION Tooth Mousse can reduce enamel demineralization and promoting remineralization in vitro Casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) slows the progression of caries and remineralizes enamel subsurface lesions . The aim of this study was to determine the ability of CPP-ACP to increase the incorporation of fluoride into plaque and to promote enamel remineralization in situ . R and omized , double-blind , cross-over studies involved mouthrinses and dentifrices containing CPP-ACP and fluoride . The mouthrinses were used for 60 sec , three times/day for 5 days , and supragingival plaque was collected and analyzed for F. The dentifrices were rinsed as a water slurry for 60 sec four times/day for 14 days in an in situ model . The addition of 2 % CPP-ACP to the 450-ppm-F mouthrinse significantly increased the incorporation of fluoride into plaque . The dentifrice containing 2 % CPP-ACP produced a level of remineralization similar to that achieved with a dentifrice containing 2800 ppm F. The dentifrice containing 2 % CPP-ACP plus 1100 ppm F was superior to all other formulations The purpose of this study was to determine the efficacy of fluoride varnish ( 5 % sodium fluoride , Duraphat ® , Colgate ) in reverting white spot lesions ( WSLs ) after fixed orthodontic treatment . This study was a r and omized , parallel group , controlled clinical trial . Using saline solution as control , 110 participants ( mean age ± st and ard deviation : 16.6 ± 3.2 years ) ranging from 12 to 22 years old were r and omly assigned to either the test group ( group 1 ) or the control group ( group 2 ) . Application of fluoride varnish or saline was applied onto tooth surfaces with WSLs every month during the first 6 months after debonding . The labial ( buccal ) surfaces of the teeth were assessed by the use of a DIAGNOdent pen ( DD ) at the baseline , 3- and 6-month follow-up visits . After 6 months , 96 subjects with a total of 209 study teeth ( 47 subjects , 104 teeth in group 1 ; 49 subjects , 105 teeth in group 2 ) remained . The WSLs had a mean DD reading at baseline of 17.66 ± 5.36 in group 1 and 16.19 ± 5.70 in group 2 , which decreased by 5.78 and 2.44 , respectively , at the 3-month follow-up visit and decreased by 7.56 and 3.09 , respectively , at the 6-month follow-up visit . The mean baseline DD readings in the two groups were similar ( t test , P > 0.05 ) . There was statistically significant differences between the mean DD readings of the two groups at the 3-month ( P < 0.05 ) and at the 6-month follow-up visits ( P < 0.01 ) . Topical fluoride varnish application is effective in reversing WSLs after debonding and should be advocated as a routine caries prevention measure after orthodontic treatment OBJECTIVE To compare the effects of sodium fluoride mouth rinse , casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) , and the microabrasion technique in treating white spot lesions . MATERIAL S AND METHODS The study population consisted of 80 patients ( 46 females , 34 males ; 966 affected teeth ) who had developed multiple decalcified enamel lesions after fixed orthodontic therapy . The study population was divided into four groups of 20 patients each . The control group ( group I ) participants were to just brush their teeth , the fluoride group ( group II ) participants were instructed to use 20 ml of neutral 0.025 % sodium fluoride rinse , the participants in the CPP-ACP group ( group III ) were instructed to use tooth mousse twice a day in addition to fluoride toothpaste for 6 months , and the participants in the microabrasion group ( group IV ) were to undergo treatment by the microabrasion technique , which is a commonly used mixture of 18 % hydrochloric acid . Data were analyzed with the generalized linear mixed model and Tukey HSD at the P < .05 level . RESULTS The area of the white spot lesions decreased significantly in all groups . Inter group differences in the treatment success rates were significant . The highest success rate was observed for group IV ( 97 % ) . The success rate of group III ( 58 % ) was significantly higher than that of groups II ( 48 % ) and I ( 45 % ) . CONCLUSIONS The use of CPP-ACP can be more beneficial than fluoride rinse for postorthodontic remineralization . Microabrasion is an effective treatment for cosmetic improvement of long-st and ing white spot lesions The aim of this study was to evaluate the remineralization potential of three silica-containing NaF dentifrice systems in an intraoral model . Subjects ( N = 30 ) in this r and omized , three-phase , 28-day , crossover study served as their own control . Each participant wore a customized orthodontic appliance attached to a m and ibular molar and contained one tooth block with caries-like lesion . For each phase , participants engaged in twice-daily brushing for 2 min with one of the following dentifrices : 500 ppm F , 500 ppm F plus functionalized β-tricalcium phosphate ( fTCP ) , and a clinical ly proven 1,100 ppm F. After each phase , appliances were removed , and specimens were analyzed using surface microhardness ( SMH ) , transverse microradiography ( TMR ) , and cross-sectional microhardness ( CSMH ) . Statistically significant ( p < 0.05 ) remineralization of white-spot lesions relative to baseline occurred for each dentifrice as determined with SMH and TMR . No significant differences ( p > 0.05 ) in SMH were found among the three groups , but trending revealed the 500 ppm F plus fTCP produced 26 % and 27 % greater SMH recovery relative to 500 and 1,100 ppm F , respectively . Similarly , no significant differences ( p > 0.05 ) in TMR were found among the groups . However , the 500 ppm F plus fTCP dentifrice produced 10 % and 38 % greater mineral recovery relative to 500 and 1,100 ppm F , respectively , while reducing the lesion depth 30 % and 52 % , respectively . Significant differences ( p < 0.05 ) in CSMH existed among the three dentifice groups at different enamel depths , but statistical differences ( p < 0.05 ) in relative lesion size were only found between 500 ppm F plus fTCP and 500 ppm F. The combination of fTCP and fluoride in a single-compartment , water-based dentifrice can cooperate with fluoride to produce significant remineralization . These results suggest that the combination of 500 ppm F with fTCP may provide comparable anticaries benefits relative to a 1,100 ppm F dentifrice OBJECTIVE To examine the effects of application of casein phosphopeptide amorphous calcium phosphate ( CPP-ACP ) paste and microabrasion treatment on the regression of white spot lesions ( WSLs ) . MATERIAL S AND METHODS Artificially-induced WSLs in bovine enamel were r and omly assigned to one of four treatment groups : CPP-ACP paste only , microabrasion only , microabrasion and CPP-ACP , and a control . Sample s were treated with each regimen twice daily for 2 weeks and stored in remineralizing solution between the treatments . Quantitative light-induced fluorescence was used to measure changes in fluorescence , which indicate changes in mineral content of WSLs immediately before ( T1 ) and 2 weeks after treatment ( T2 ) . A two-within-subject factor analysis of variance was used to analyze the significance of any changes in mineral content of the lesions from T1 to T2 . RESULTS There was a statistically significant ( P < .05 ) gain in fluorescence associated with the microabrasion only , as well as the microabrasion and CPP-ACP treatments . The changes in fluorescence for the CPP-ACP treatment alone were not statistically significant ( P = .40 ) . CONCLUSIONS CPP-ACP paste alone does not significantly improve the fluorescence value ( ie , the mineral content ) of WSLs . Within the limitations of this in vitro study , microabrasion treatment with or without CPP-ACP improved the fluorescence and thus reduced WSLs Objective To compare and measure the changes in size of post-orthodontic demineralized white lesion enamel lesions treated with a low fluoride ( 50 ppm ) versus a non-fluoride mouthrinse/toothpaste regime . Study design An experimental double-blind prospect i ve r and omized clinical controlled trial . Setting A university dental school orthodontic clinic ( Sheffield , UK ) . Participants Twenty-six patients identified as having post-orthodontic demineralized white lesions on removal of their fixed appliance . Method and interventions The participants were r and omly and blindly assigned to either a low fluoride mouthrinse/toothpaste treatment regime or an inactive control . Computerized image analysis of calibrated photographic images taken under polarized light were used to measure the lesions . Outcome measures Lesion size and proportion ( DWL%t ) and percentage reduction ( ADPR ) at debond , and at 12 and 26 weeks later . Results Five participants dropped out of the study , 12 had the low fluoride regime and 9 did not . As a percentage of the total labial tooth area ( DWL%t ) the mean size of the lesions at debond was 8.1 % ( SD 3.7 ) . After 12 weeks the mean size of lesion had reduced to 4.6 % ( SD 2.6 ) , which was a significant reduction ( p=0.03 ) . After 26 weeks the mean size was 3.5 % ( SD 2.1 ) , which was a very significant reduction ( p<0.003 ) . This confirmed statistically that post-orthodontic demineralized white lesions do reduce in size with time reflecting remineralization or other enamel surface changes . Intervention using a test low fluoride mouthrinse/toothpaste combination at 26 weeks showed an average difference percentage reduction ( ADPR ) of 54.3 % ( Upper 95 % CI=62.08 , Lower 95 % CI=46.44 % ) compared with a non-active control combination , which showed an ADPR of 66.1 % ( Upper 95 % CI=77.74 , Lower 95 % CI=54.51 % ) . This failed to show any differences or therapeutic affect . Conclusions Post-orthodontic demineralized white lesions reduced in size during the 6 months following treatment by approximately half the original size . There was no clinical advantage in using the low fluoride formulation of mouthrinse/toothpaste in this study INTRODUCTION White spots ( WS ) related to orthodontic treatment are severe cariologic and cosmetic complications , but they are shown to be partially reduced by remineralization or abrasion in short-term follow-ups . In this prospect i ve study , we quantitatively analyzed changes in WS in general and in treatment-related white spot lesions ( WSL ) during orthodontic treatment and at a 12-year follow-up after treatment . In addition , we quantitatively compared the effects of an acrylic bonding material vs a glass ionomer cement ( GIC ) on WSL . METHODS Sum areas of WS and WSL were calculated on scans of st and ardized photos of the vestibular surfaces of 4 teeth in consecutive orthodontic patients ( median treatment time , 1.7 years ) bonded with the 2 material s in a split-mouth design . Comparisons were made in 59 patients before treatment ( BF ) , at debonding ( T0 ) , at 1 year ( T1 ) , and at 2 years ( T2 ) , and in 30 patients at a 12-year follow-up ( T3 ) with the Friedman test followed by pairwise comparisons with the Wilcoxon matched-pairs signed rank test . Differences of the effects of acrylic vs GIC on the sum areas of WSL were tested for each observation period with the Mann-Whitney U test . RESULTS Increases in the sum areas of WS and WSL from BF to T0 ( P < 0.001 ) were followed by significant decreases at T1 ( P < 0.001 ) and T2 ( P < 0.01 for WS ; P < 0.001 for WSL ) . Significant changes were also found in the sum areas for WS at T3 compared with T2 ( P < 0.01 ) , but not for WSL ( P = 0.328 ) . The sum areas of WS and WSL at T3 did not return to BF levels ( P < 0.001 ) . Sum areas of WSL were higher for surfaces bonded with acrylic compared with GIC for each observation period from BF to T2 ( P > 0.001 ) , and from T2 to T3 ( P > 0.05 ) . CONCLUSIONS Although significantly reduced during the 12-year follow-up and significantly lower with the GIC than the acrylic material at bonding , WSL are a cariologic and cosmetic problem for many orthodontic patients Orthodontic patients have an increased risk of white-spot lesion formation . A clinical trial was conducted to test whether , in a post-orthodontic population using fluoride toothpastes and receiving supervised fluoride mouthrinses , more lesions would regress in participants using a remineralizing cream containing casein phosphopeptide- amorphous calcium phosphate compared with a placebo . Forty-five participants ( aged 12–18 yrs ) with 408 white-spot lesions were recruited , with 23 participants r and omized to the remineralizing cream and 22 to the placebo . Product was applied twice daily after fluoride toothpaste use for 12 weeks . Clinical assessment s were performed according to ICDAS II criteria . Transitions between examinations were coded as progressing , regressing , or stable . Ninety-two percent of lesions were assessed as code 2 or 3 . For these lesions , 31 % more had regressed with the remineralizing cream than with the placebo ( OR = 2.3 , P = 0.04 ) at 12 weeks . Significantly more post-orthodontic white-spot lesions regressed with the remineralizing cream compared with a placebo over 12 weeks This study aims to investigate the effect of topical applications of 10 % casein phosphopeptide – amorphous calcium phosphate ( CPP – ACP ) on white spot lesions ( WSL ) detected after treatment with fixed orthodontic appliances . Sixty healthy adolescents with ≥1 clinical ly visible WSL at debonding were recruited and r and omly allocated to a r and omised controlled trial with two parallel groups . The intervention group was instructed to topically apply a CPP – ACP -containing agent ( Tooth Mousse , GC Europe ) once daily and the subjects of the control group brushed their teeth with st and ard fluoride toothpaste . The intervention period was 4 weeks and the endpoints were quantitative light-induced fluorescence ( QLF ) on buccal surfaces of the upper incisors , cuspids and first premolars and visual scoring from digital photos . The attrition rate was 15 % , mostly due to technical errors , and 327 lesions were included in the final evaluation . A statistically significant ( p < 0.05 ) regression of the WSL was disclosed in both study groups compared to baseline , but there was no difference between the groups . The mean area of the lesions decreased by 58 % in the CPP – ACP group and 26 % in the fluoride group ( p = 0.06 ) . The QLF findings were largely reflected by the clinical scores . No side effects were reported . Topical treatment of white spot lesions after debonding of orthodontic appliances with a casein phosphopeptide-stabilised amorphous calcium phosphate agent result ed in significantly reduced fluorescence and a reduced area of the lesions after 4 weeks as assessed by QLF . The improvement was however not superior to the “ natural ” regression following daily use of fluoride toothpaste The effects of casein phosphopeptide amorphous calcium fluoride phosphate ( CPP-ACFP ) paste vs. control paste on the remineralization of white spot caries lesions and on plaque composition were tested in a double-blind prospect i ve r and omized clinical trial . Fifty-four orthodontic patients , with multiple white spot lesions observed upon the removal of fixed appliances , were followed up for 3 months . Subjects were included and r and omly assigned to either CPP-ACFP paste or control paste , for use supplementary to their normal oral hygiene . Caries regression was assessed on quantitative light-induced fluorescence ( QLF ) images captured directly after debonding and 6 and 12 wk thereafter . The total counts and proportions of aciduric bacteria , Streptococcus mutans , and Lactobacillus spp . were measured in plaque sample s obtained just before debonding , and 6 and 12 wk afterwards . A significant decrease in fluorescence loss was found with respect to baseline for both groups and no difference was found between groups . The size of the lesion area did not change significantly over time or between the groups . The percentages of aciduric bacteria and of S. mutans decreased from 47.4 to 38.1 % and from 9.6 to 6.6 % , respectively . No differences were found between groups . We observed no clinical advantage for use of the CPP-ACFP paste supplementary to normal oral hygiene over the time span of 12 wk PURPOSE To determine the value of clinical application of CPP-ACP during orthodontic treatment with fixed appliance . METHODS Seventy-five subjects were divided r and omly into three groups , the control group , experimental group A and experimental group B. The control group were emphasized on daily oral hygiene . Experimental group A used fluor protector every three months under the dentist 's guidance . Experimental group B used Casein phosphopeptide amorphous calcium phosphate(CCP-ACP ) once a day . After finishing the orthodontic treatment , photos were taken under the same condition , then the degree of the enamel 's demineralization was examined and the enamel decalcification index(EDI ) was calculated . SPSS11.0 software package was used for statistical analysis . RESULTS (1)The incidence of three groups ' enamel decalcification declined in sequence as the control group(60%),experimental group A ( 36 % ) , experimental group B (32%).(2)The incidence of the teeth 's enamel calcification of three groups declined in sequence as the control group(14.7%),experimental group A ( 8.46 % ) , experimental group B ( 7.72 % ) , the difference between the control group and two experimental groups was significant , while no significant difference was found between the two experimental groups.(3(EDI of the control group was 0.155+/-0.023 , EDI of the experimental group A was 0.082+/-0.009,while EDI of the experimental group B was 0.078+/-0.006 . The difference between the control group and two experimental groups was statistically significant , while was not statistically significant between the two experimental groups . CONCLUSIONS The application of fluor protector and CPP-ACP can improve the mineralization of the teeth during orthodontic treatment with fixed appliance . CPP-ACP is more convenient for the patients to use . Supported by Research Fund of Bureau of Science and Technology of Futian District Shenzhen City(Grant No . FTWS056 ) This pilot study investigated the effect of a remineralizing fluoride dentifrice ( Enamelon ) on newly formed incipient carious lesions using two methods of application . Teenage orthodontic patients with obvious white spot lesions on their teeth were selected to begin treatment within 30 days after deb and ing . At baseline , the surface enamel of the test teeth was cleaned by air etching with 50 microns alumina at 150 psi . Lesion size ( mm2 ) was measured using a calibrated periodontal probe and surface appearance was quantified as shiny ( 0 ) , dull ( 1 ) , or chalky ( 2 ) . Twice daily for 3 months , one group with a total of 27 lesions brushed with the remineralizing dentifrice , while a second group with 41 total lesions brushed and used a mouth tray to apply the paste directly to the lesions for 5 min . In order to promote treatment compliance , test group assignment was based on subject and parental preference . After 1 , 2 , and 3 months , lesion size was reduced by 5 % ( ns ) , 10 % ( p < 0.05 ) and 22 % ( p < 0.01 ) , respectively , for the brushing group , and 16 % ( p < 0.05 ) , 37 % ( p < 0.01 ) and 30 % ( p < 0.01 ) for the combined brushing and tray group , respectively . The dull appearance of the lesions treated by brushing improved slightly over 3 months . However , the lesions receiving combined brushing and tray applications became significantly ( p < 0.01 ) less dull by 28 % , 44 % and 61 % after 1 , 2 , and 3 months , respectively , indicating the formation of a shiny , intact surface layer . In conclusion , brushing with a remineralizing dentifrice significantly reduced the size of new orthodontic white spots within 2 months , while brushing combined with topical tray applications reduced lesion size within 1 month with concomitant formation of a shiny enamel surface layer . Thus , the combined brushing and mouth tray treatment significantly accelerated the remineralization process The aim of this study was to investigate differences in shape and size characteristics between developmental opacities and post-orthodontic white enamel lesions using computerized image analysis . Material , in the form of 35 mm slides , was obtained from the archive of photographic patient records in the orthodontic clinic at the Charles Clifford Dental Hospital . Images of 30 teeth with developmental white lesions and 30 teeth with post-orthodontic white lesions were selected using strict inclusion and exclusion criteria . The slides were converted to a digital format , coded , placed in a r and om order and analysed blindly using a computerized image analysis system by one clinician . After a 2 week interval , the images were recorded , placed in a new r and om order and the measurements repeated . The outcome measures were : area and luminance proportionality , and the shape of the perimeter line ( expressed as the mathematical factor , roundness ) . Reproducibility was assessed by a paired sample s t-test for systematic error and the intra-class correlation coefficient ( ICC ) for r and om error . Differences between groups were tested using the Mann-Whitney U-test for non-parametric data . Reproducibility was substantial for all measurements except for developmental white lesion roundness , which was moderate . There was a statistically significant difference between developmental white opacities and post-orthodontic white lesions for measurements of luminance intensity , proportionality ( P = 0.002 ) and roundness ( P = 0.001 ) . Developmental white opacities had a higher luminance ( i.e. were whiter ) and the boundaries were more circular in shape than the post-orthodontic lesions . Roundness is a useful measure when distinguishing developmental and post-orthodontic demineralization White spot or areas of decalcification are carious lesions of varying extent . The incidence and severity of white spots after a full term of orthodontic treatment were studied among patients in the separate private practice s of two of the authors . To establish a base line of comparison , the presence of white spots in a r and om sample of untreated persons was observed . The incidence of white spots among patients treated by a multibonded technique was recorded at the time of debonding . In addition , white spots were sought in the before- and after-treatment Kodachrome slides of persons whose maxillary incisors had been h and ed . It was found that individual teeth , b and ed or bonded , exhibited significantly more white spot formation than was found in the control group . For the teeth studied , there was no difference in white spot formation in those that were b and ed or bonded . The labiogingival area of the maxillary lateral incisors had the highest incidence of white spots . When studied by segments , the highest incidence occurred among the maxillary incisors ; the lowest was in the maxillary posterior segment . No white spots were found on the lingual surfaces of m and ibular canines and incisors after prolonged use of a canine-to-canine bonded retainer . These findings suggest a relationship between resistance to white spot formation and the rate of salivary flow . Despite the lack of any preventive fluoride program among the study groups , 50 % of the patients demonstrated resistance to white spot formation . The obvious degree of latrogenic damage during orthodontic treatment suggests the need for preventive programs using fluoride . Further clinical research is needed |
12,474 | 31,890,897 | There was a statistically non-significant increase in all-cause mortality .
The results showed that in terms of lung cancer mortality reduction LDCT was ranked as the best screening strategy , CXR screening as the worst strategy and usual care intermediate . | Background Diagnosis of lung cancer frequently occurs in its later stages .
Low-dose computed tomography ( LDCT ) could detect lung cancer early . | BACKGROUND Low-dose CT screening is recommended for individuals at high risk of developing lung cancer . However , CT screening does not detect all lung cancers : some might be missed at screening , and others can develop in the interval between screens . The NELSON trial is a r and omised trial to assess the effect of screening with increasing screening intervals on lung cancer mortality . In this prespecified analysis , we aim ed to assess screening test performance , and the epidemiological , radiological , and clinical characteristics of interval cancers in NELSON trial participants assigned to the screening group . METHODS Eligible participants in the NELSON trial were those aged 50 - 75 years , who had smoked 15 or more cigarettes per day for more than 25 years or ten or more cigarettes for more than 30 years , and were still smoking or had quit less than 10 years ago . We included all participants assigned to the screening group who had attended at least one round of screening . Screening test results were based on volumetry using a two-step approach . Initially , screening test results were classified as negative , indeterminate , or positive based on nodule presence and volume . Subsequently , participants with an initial indeterminate result underwent follow-up screening to classify their final screening test result as negative or positive , based on nodule volume doubling time . We obtained information about all lung cancer diagnoses made during the first three rounds of screening , plus an additional 2 years of follow-up from the national cancer registry . We determined epidemiological , radiological , participant , and tumour characteristics by reassessing medical files , screening CTs , and clinical CTs . The NELSON trial is registered at www.trialregister.nl , number IS RCT N63545820 . FINDINGS 15,822 participants were enrolled in the NELSON trial , of whom 7915 were assigned to low-dose CT screening with increasing interval between screens , and 7907 to no screening . We included 7155 participants in our study , with median follow-up of 8·16 years ( IQR 7·56 - 8·56 ) . 187 ( 3 % ) of 7155 screened participants were diagnosed with 196 screen-detected lung cancers , and another 34 ( < 1 % ; 19 [ 56 % ] in the first year after screening , and 15 [ 44 % ] in the second year after screening ) were diagnosed with 35 interval cancers . For the three screening rounds combined , with a 2-year follow-up , sensitivity was 84·6 % ( 95 % CI 79·6 - 89·2 ) , specificity was 98·6 % ( 95 % CI 98·5 - 98·8 ) , positive predictive value was 40·4 % ( 95 % CI 35·9 - 44·7 ) , and negative predictive value was 99·8 % ( 95 % CI 99·8 - 99·9 ) . Retrospective assessment of the last screening CT and clinical CT in 34 patients with interval cancer showed that interval cancers were not visible in 12 ( 35 % ) cases . In the remaining cases , cancers were visible when retrospectively assessed , but were not diagnosed because of radiological detection and interpretation errors ( 17 [ 50 % ] ) , misclassification by the protocol ( two [ 6 % ] ) , participant non-compliance ( two [ 6 % ] ) , and non-adherence to protocol ( one [ 3 % ] ) . Compared with screen-detected cancers , interval cancers were diagnosed at more advanced stages ( 29 [ 83 % ] of 35 interval cancers vs 44 [ 22 % ] of 196 screen-detected cancers diagnosed in stage III or IV ; p<0·0001 ) , were more often small-cell carcinomas ( seven [ 20 % ] vs eight [ 4 % ] ; p=0·003 ) and less often adenocarcinomas ( nine [ 26 % ] vs 102 [ 52 % ] ; p=0·005 ) . INTERPRETATION Lung cancer screening in the NELSON trial yielded high specificity and sensitivity , with only a small number of interval cancers . The results of this study could be used to improve screening algorithms , and reduce the number of missed cancers . FUNDING Zorgonderzoek Nederl and Medische Wetenschappen and Koningin Wilhelmina Fonds BACKGROUND The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening . The advent of low-dose helical computed tomography ( CT ) altered the l and scape of lung-cancer screening , with studies indicating that low-dose CT detects many tumors at early stages . The National Lung Screening Trial ( NLST ) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer . METHODS From August 2002 through April 2004 , we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers . Participants were r and omly assigned to undergo three annual screenings with either low-dose CT ( 26,722 participants ) or single-view posteroanterior chest radiography ( 26,732 ) . Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31 , 2009 . RESULTS The rate of adherence to screening was more than 90 % . The rate of positive screening tests was 24.2 % with low-dose CT and 6.9 % with radiography over all three rounds . A total of 96.4 % of the positive screening results in the low-dose CT group and 94.5 % in the radiography group were false positive results . The incidence of lung cancer was 645 cases per 100,000 person-years ( 1060 cancers ) in the low-dose CT group , as compared with 572 cases per 100,000 person-years ( 941 cancers ) in the radiography group ( rate ratio , 1.13 ; 95 % confidence interval [ CI ] , 1.03 to 1.23 ) . There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group , representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0 % ( 95 % CI , 6.8 to 26.7 ; P=0.004 ) . The rate of death from any cause was reduced in the low-dose CT group , as compared with the radiography group , by 6.7 % ( 95 % CI , 1.2 to 13.6 ; P=0.02 ) . CONCLUSIONS Screening with the use of low-dose CT reduces mortality from lung cancer . ( Funded by the National Cancer Institute ; National Lung Screening Trial Clinical Trials.gov number , NCT00047385 . ) BACKGROUND The Mayo Lung Project ( MLP ) was a r and omized , controlled clinical trial of lung cancer screening that was conducted in 9211 male smokers between 1971 and 1983 . The intervention arm was offered chest x-ray and sputum cytology every 4 months for 6 years ; the usual-care arm was advised at trial entry to receive the same tests annually . No lung cancer mortality benefit was evident at the end of the study . We have extended follow-up through 1996 . METHODS A National Death Index-PLUS search was used to assign vital status and date and cause of death for 6523 participants with unknown information . The median survival for lung cancer patients diagnosed before July 1 , 1983 , was calculated by use of Kaplan-Meier estimates . Survival curves were compared with the log-rank test . RESULTS The median follow-up time was 20.5 years . Lung cancer mortality was 4.4 ( 95 % confidence interval [ CI ] = 3.9 - 4.9 ) deaths per 1000 person-years in the intervention arm and 3.9 ( 95 % CI = 3.5 - 4.4 ) in the usual-care arm ( two-sided P : for difference = .09 ) . For participants diagnosed with lung cancer before July 1 , 1983 , survival was better in the intervention arm ( two-sided P : = .0039 ) . The median survival for patients with resected early-stage disease was 16.0 years in the intervention arm versus 5.0 years in the usual-care arm . CONCLUSIONS Extended follow-up of MLP participants did not reveal a lung cancer mortality reduction for the intervention arm . Similar mortality but better survival for individuals in the intervention arm indicates that some lesions with limited clinical relevance may have been identified in the intervention arm RATIONALE Screening for lung cancer with modern imaging technology may decrease lung cancer mortality , but encouraging results have only been obtained in uncontrolled studies . OBJECTIVES To explore the effect of screening with low-dose spiral computed tomography ( LDCT ) on lung cancer mortality . Secondary endpoints are incidence , stage at diagnosis , and resectability . METHODS Male subjects , aged 60 to 75 years , smokers of 20 or more pack-years , were r and omized to screening with LDCT or control groups . All participants underwent a baseline , once-only chest X-ray and sputum cytology examination . Screening-arm subjects had LDCT upon accrual to be repeated every year for 4 years , whereas controls had a yearly medical examination only . MEASUREMENTS AND MAIN RESULTS A total of 2,811 subjects were r and omized and 2,472 were enrolled ( LDCT , 1,276 ; control , 1,196 ) . After a median follow-up of 33 months , lung cancer was detected in 60 ( 4.7 % ) patients receiving LDCT and 34 ( 2.8 % ) control subjects ( P = 0.016 ) . Resectability rates were similar in both groups . More patients with stage I disease were detected by LDCT ( 54 vs. 34 % ; P = 0.06 ) and fewer cases were detected in the screening arm due to intercurrent symptoms . However , the number of advanced lung cancer cases was the same as in the control arm . Twenty patients in the LDCT group ( 1.6 % ) and 20 controls ( 1.7 % ) died of lung cancer , whereas 26 and 25 died of other causes , respectively . CONCLUSIONS The mortality benefit from lung cancer screening by LDCT might be far smaller than anticipated Purpose Low-dose multislice-CT ( MSCT ) detects many early-stage lung cancers with good prognosis , but whether it decreases lung cancer mortality and at which costs is yet insufficiently explored . Scope of the present study is to examine within a common European effort whether MSCT screening is capable to reduce the lung cancer mortality by at least 20 % and at which amount of undesired side effects this could be achieved . Methods Overall 4,052 heavy smoking men and women were recruited by a population -based approach and r and omized into a screening arm with five annual MSCT screens and an initial quit-smoking counseling , and a control arm with initial quit-smoking counseling and five annual question naire inquiries . Results In the first screening round , 2,029 participants received a MSCT providing 1,488 negative and 540 suspicious screens with early recalls ( early recall rate 26.6 % ) leading to 31 biopsies ( biopsy rate 1.5 % ) and 22 confirmed lung cancers ( detection rate 1.1 % ) . Among the lung cancers , 15 were adenocarcinomas , 3 squamous cell carcinomas , one small-cell lung cancer , and 3 others , whereby 18 were in clinical stage I , one in stage II , and 3 in stage III . One interval cancer occurred . Conclusions The indicated performance indicators fit into the range observed in comparable trials . The study continues finalizing the second screening round and for the first participants even the last screening round . The unresolved issue of the precise amount of side effects and the high early recall rate precludes currently the recommendation of MSCT as screening tool for lung cancer In a r and omized prospect i ve study of lung cancer detection in a high-risk population of over 6000 heavy smokers semiannual screening by X-ray and sputum cytology was compared to screening at a 3-year interval . The comparison of Kaplan-Meier estimates of survival curves done without and with correcting for lead-time bias disclosed a rather important impact of lead-time bias on survival comparisons . On the contrary , controlling for possible length bias had no obvious effect on the shape of survival curves . The evaluation of mortality from lung cancer , being used as a basic criterion , indicated no traceable benefit from semiannual screening . The higher incidence of lung cancer in the frequently screened group was paralleled by a higher mortality . It is concluded that currently available screening techniques will not solve the problem of lung cancer mortality in smokers . The results underline the importance of primary prevention for lung cancer The study was launched in the mid‐1970s to explore the capability of screening by chest X‐ray and sputum cytology to be used as an effective component of the lung cancer control program in the Czech Republic , a Central European country with a high and increasing occurrence of lung cancer in men at that time . A complementary objective of this report is to ascertain whether the cumulative numbers of lung cancer deaths would equalize in the two r and omized groups during a prolonged follow‐up period THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard Wound-care journals contain abundant reports of trials , but not all report a satisfactory methodology . Systematic review s of wound-care trials have highlighted many areas for improvement , and the National Institute for Clinical Excellence ( NICE ) guidelines recommend that primary research in the field of pressure ulcer prevention should adhere more closely to current method ological st and ards in terms of conduct and reporting . The CONSORT tool was developed to help achieve these improvements in the design and reporting of r and omised controlled trials ( RCTs ) Introduction : Lung cancer screening with low dose computed tomography ( CT ) has not yet been evaluated in r and omized clinical trials , although several are underway . Methods : In The Danish Lung Cancer Screening Trial , 4104 smokers and previous smokers from 2004 to 2006 were r and omized to either screening with annual low dose CT scans for 5 years or no screening . A history of cigarette smoking of at least 20 pack years was required . All participants have annual lung function tests , and question naires regarding health status , psychosocial consequences of screening , smoking habits , and smoking cessation . Baseline CT scans were performed in 2052 participants . Pulmonary nodules were classified according to size and morphology : ( 1 ) Nodules smaller than 5 mm and calcified ( benign ) nodules were tabulated , ( 2 ) Noncalcified nodules between 5 and 15 mm were rescanned after 3 months . If the nodule increased in size or was larger than 15 mm the participant was referred for diagnostic workup . Results : At baseline 179 persons showed noncalcified nodules larger than 5 mm , and most were rescanned after 3 months : The rate of false-positive diagnoses was 7.9 % , and 17 individuals ( 0.8 % ) turned out to have lung cancer . Ten of these had stage I disease . Eleven of 17 lung cancers at baseline were treated surgically , eight of these by video assisted thoracic surgery resection . Conclusions : Screening may facilitate minimal invasive treatment and can be performed with a relatively low rate of false-positive screen results compared with previous studies on lung cancer screening Introduction : Recruitment and nodule management are critical issues of lung cancer screening with low-dose computed tomography ( LDCT ) . We report subjects ’ compliance and results of LDCT screening and management protocol in the active arm of the ITALUNG trial . Methods : Three thous and two hundred six smokers or former smokers invited by mail were r and omized to receive four annual LDCT ( n = 1613 ) or usual care ( n = 1593 ) . Management protocol included follow-up LDCT , 2-[18F]fluoro-2-deoxy-D glucose positron emission tomography ( FDG-PET ) , and CT-guided fine-needle aspiration biopsy ( FNAB ) . Results : One thous and four hundred six subjects ( 87 % ) underwent baseline LDCT , and 1263 ( 79 % ) completed four screening rounds . LDCT was positive in 30.3 % of the subjects at baseline and 15.8 % subsequently . Twenty-one lung tumors in 20 subjects ( 1.5 % detection ) were found at baseline , and 20 lung tumors in 18 subjects ( 0.5 % detection ) in subsequent screening rounds . Ten of 18 prevalent ( 55 % ) and 13 of 17 incident ( 76 % ) non – small-cell cancers were in stage I. Interval growth enabled diagnosis of lung cancer in 16 subjects ( 42 % ) , but at least one follow-up LDCT was obtained in 741 subjects ( 52.7 % ) over the screening period . FDG-PET obtained in 6.5 % of subjects had 84 % sensitivity and 90 % specificity for malignant lesions . FNAB obtained in 2.4 % of subjects showed 90 % sensitivity and 88 % specificity . Positivity of both FDG-PET and FNAB invariably predicted malignancy . Surgery for benign lesions was performed on four subjects ( 10 % of procedures ) but followed protocol violations on three subjects . Conclusions : High-risk subjects recruited by mail who entered LDCT screening showed a high and stable compliance . Efficacy of screening is , however , weakened by low detection rate and specificity . Adhesion to management protocol might lessen surgery for benign lesions Objectives To examine whether age at entry , history of cigarette smoking , exposure to non-tobacco lung carcinogens , or previous pulmonary illnesses were confounders or effect modifiers of the relation between screening and lung cancer mortality in the Mayo Lung Project . Setting —The Mayo Lung Project was a r and omised , controlled , clinical trial conducted between 1971 and 1986 in 9211 male smokers over the age of 45 in Minnesota ( USA ) . The group screened received chest x ray examination and sputum cytology every four months for six years . The unscreened group were recommended to obtain usual care ( annual chest x ray examination and sputum cytology ) . After follow up , lung cancer mortality was similar in both groups . Methods —Proportional hazard models were used to analyse data . A variable was considered a confounder if its inclusion in a model changed the rate ratio for screening by more than 15 % ; a variable was considered an effect modifier if its stratum-specific rate ratio for screening differed by a factor of two . Results None of the four aforementioned variables changed the rate ratio associated with screening ( 1.07 ) by more than 2 % . The effect of screening may have differed by years smoked ( rate ratio for smoking fewer than 30 years 2.4 ; rate ratio for smoking 30 or more years 1.0 ) , though we suspect that this result occurred by chance . Conclusion Adjustment for or stratification by four established lung cancer risk factors did not alter the original findings of the Mayo Lung Project BACKGROUND Lung cancer kills more people than any other cancer in the UK ( 5-year survival < 13 % ) . Early diagnosis can save lives . The USA-based National Lung Cancer Screening Trial reported a 20 % relative reduction in lung cancer mortality and 6.7 % all-cause mortality in low-dose computed tomography (LDCT)-screened subjects . OBJECTIVES To ( 1 ) analyse LDCT lung cancer screening in a high-risk UK population , determine optimum recruitment , screening , reading and care pathway strategies ; and ( 2 ) assess the psychological consequences and the health-economic implication s of screening . DESIGN A pilot r and omised controlled trial comparing intervention with usual care . A population -based risk question naire identified individuals who were at high risk of developing lung cancer ( ≥ 5 % over 5 years ) . SETTING Thoracic centres with expertise in lung cancer imaging , respiratory medicine , pathology and surgery : Liverpool Heart & Chest Hospital , Merseyside , and Papworth Hospital , Cambridgeshire . PARTICIPANTS Individuals aged 50 - 75 years , at high risk of lung cancer , in the primary care trusts adjacent to the centres . INTERVENTIONS A thoracic LDCT scan . Follow-up computed tomography ( CT ) scans as per protocol . Referral to multidisciplinary team clinics was determined by nodule size criteria . MAIN OUTCOME MEASURES Population -based recruitment based on risk stratification ; management of the trial through web-based data base ; optimal characteristics of CT scan readers ( radiologists vs. radiographers ) ; characterisation of CT-detected nodules utilising volumetric analysis ; prevalence of lung cancer at baseline ; sociodemographic factors affecting participation ; psychosocial measures ( cancer distress , anxiety , depression , decision satisfaction ) ; and cost-effectiveness modelling . RESULTS A total of 247,354 individuals were approached to take part in the trial ; 30.7 % responded positively to the screening invitation . Recruitment of participants result ed in 2028 in the CT arm and 2027 in the control arm . A total of 1994 participants underwent CT scanning : 42 participants ( 2.1 % ) were diagnosed with lung cancer ; 36 out of 42 ( 85.7 % ) of the screen-detected cancers were identified as stage 1 or 2 , and 35 ( 83.3 % ) underwent surgical resection as their primary treatment . Lung cancer was more common in the lowest socioeconomic group . Short-term adverse psychosocial consequences were observed in participants who were r and omised to the intervention arm and in those who had a major lung abnormality detected , but these differences were modest and temporary . Rollout of screening as a service or design of a full trial would need to address issues of outreach . The health-economic analysis suggests that the intervention could be cost-effective but this needs to be confirmed using data on actual lung cancer mortality . CONCLUSIONS The UK Lung Cancer Screening ( UKLS ) pilot was successfully undertaken with 4055 r and omised individuals . The data from the UKLS provide evidence that adds to existing data to suggest that lung cancer screening in the UK could potentially be implemented in the 60 - 75 years age group , selected via the Liverpool Lung Project risk model version 2 and using CT volumetry-based management protocol s. FUTURE WORK The UKLS data will be pooled with the NELSON ( Nederl and s Leuvens Longkanker Screenings Onderzoek : Dutch-Belgian R and omised Lung Cancer Screening Trial ) and other European Union trials in 2017 which will provide European mortality and cost-effectiveness data . For now , there is a clear need for mortality results from other trials and further research to identify optimal methods of implementation and delivery . Strategies for increasing uptake and providing support for underserved groups will be key to implementation . TRIAL REGISTRATION Current Controlled Trials IS RCT N78513845 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 20 , No. 40 . See the NIHR Journals Library website for further project information BACKGROUND Lung cancer is the largest contributor to mortality from cancer . The National Lung Screening Trial ( NLST ) showed that screening with low-dose helical computed tomography ( CT ) rather than with chest radiography reduced mortality from lung cancer . We describe the screening , diagnosis , and limited treatment results from the initial round of screening in the NLST to inform and improve lung-cancer-screening programs . METHODS At 33 U.S. centers , from August 2002 through April 2004 , we enrolled asymptomatic participants , 55 to 74 years of age , with a history of at least 30 pack-years of smoking . The participants were r and omly assigned to undergo annual screening , with the use of either low-dose CT or chest radiography , for 3 years . Nodules or other suspicious findings were classified as positive results . This article reports findings from the initial screening examination . RESULTS A total of 53,439 eligible participants were r and omly assigned to a study group ( 26,715 to low-dose CT and 26,724 to chest radiography ) ; 26,309 participants ( 98.5 % ) and 26,035 ( 97.4 % ) , respectively , underwent screening . A total of 7191 participants ( 27.3 % ) in the low-dose CT group and 2387 ( 9.2 % ) in the radiography group had a positive screening result ; in the respective groups , 6369 participants ( 90.4 % ) and 2176 ( 92.7 % ) had at least one follow-up diagnostic procedure , including imaging in 5717 ( 81.1 % ) and 2010 ( 85.6 % ) and surgery in 297 ( 4.2 % ) and 121 ( 5.2 % ) . Lung cancer was diagnosed in 292 participants ( 1.1 % ) in the low-dose CT group versus 190 ( 0.7 % ) in the radiography group ( stage 1 in 158 vs. 70 participants and stage IIB to IV in 120 vs. 112 ) . Sensitivity and specificity were 93.8 % and 73.4 % for low-dose CT and 73.5 % and 91.3 % for chest radiography , respectively . CONCLUSIONS The NLST initial screening results are consistent with the existing literature on screening by means of low-dose CT and chest radiography , suggesting that a reduction in mortality from lung cancer is achievable at U.S. screening centers that have staff experienced in chest CT . ( Funded by the National Cancer Institute ; NLST Clinical Trials.gov number , NCT00047385 . ) The U.S. Preventive Services Task Force ( USPSTF ) makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms . It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance . The USPSTF does not consider the costs of providing a service in this assessment . The USPSTF recognizes that clinical decisions involve more considerations than evidence alone . Clinicians should underst and the evidence but individualize decision making to the specific patient or situation . Similarly , the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms . Summary of Recommendation and Evidence The USPSTF recommends annual screening for lung cancer with low-dose computed tomography ( LDCT ) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years . Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery . ( B recommendation ) See the Clinical Considerations section for suggestions for implementation in practice . See the Figure for a summary of the recommendation and suggestions for clinical practice . Figure . Screening for lung cancer : clinical summary of U.S. Preventive Services Task Force recommendation . Appendix Table 1 describes the USPSTF grade s , and Appendix Table 2 describes the USPSTF classification of levels of certainty about net benefit . Appendix Table 1 . What the USPSTF Grade s Mean and Suggestions for Practice Appendix Table 2 . USPSTF Levels of Certainty Regarding Net Benefit Supplement . Consumer Fact Sheet . Rationale Importance Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States ( 1 ) . The most important risk factor for lung cancer is smoking , which results in approximately 85 % of all U.S. lung cancer cases ( 2 ) . Although the prevalence of smoking has decreased , approximately 37 % of U.S. adults are current or former smokers ( 2 ) . The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older . Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer . Lung cancer has a poor prognosis , and nearly 90 % of persons with lung cancer die of the disease . However , early-stage nonsmall cell lung cancer ( NSCLC ) has a better prognosis and can be treated with surgical resection . Detection Most lung cancer cases are NSCLC , and most screening programs focus on the detection and treatment of early-stage NSCLC . Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer , LDCT has greater sensitivity for detecting early-stage cancer ( 3 ) . Benefits of Detection and Early Treatment Although lung cancer screening is not an alternative to smoking cessation , the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancerrelated deaths . Direct evidence from a large , well-conducted , r and omized , controlled trial ( RCT ) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population ( 4 ) . The magnitude of benefit to the person depends on that person 's risk for lung cancer because those who are at highest risk are most likely to benefit . Screening can not prevent most lung cancerrelated deaths , and smoking cessation remains essential . Harms of Detection and Early Intervention and Treatment The harms associated with LDCT screening include false-negative and false-positive results , incidental findings , overdiagnosis , and radiation exposure . False-positive LDCT results occur in a substantial proportion of screened persons ; 95 % of all positive results do not lead to a diagnosis of cancer . In a high- quality screening program , further imaging can resolve most false-positive results ; however , some patients may require invasive procedures . The USPSTF found insufficient evidence on the harms associated with incidental findings . Overdiagnosis of lung cancer occurs , but its precise magnitude is uncertain . A modeling study performed for the USPSTF estimated that 10 % to 12 % of screen-detected cancer cases are overdiagnosedthat is , they would not have been detected in the patient 's lifetime without screening . Radiation harms , including cancer result ing from cumulative exposure to radiation , vary depending on the age at the start of screening ; the number of scans received ; and the person 's exposure to other sources of radiation , particularly other medical imaging . USPSTF Assessment The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic persons who are at high risk for lung cancer based on age , total cumulative exposure to tobacco smoke , and years since quitting smoking . The moderate net benefit of screening depends on limiting screening to persons who are at high risk , the accuracy of image interpretation being similar to that found in the NLST ( National Lung Screening Trial ) , and the resolution of most false-positive results without invasive procedures ( 4 ) . Clinical Considerations Patient Population Under Consideration The risk for lung cancer increases with age and cumulative exposure to tobacco smoke and decreases with time since quitting smoking . The best evidence for the benefit of screening comes from the NLST , which enrolled adults aged 55 to 74 years who had at least a 30 pack-year smoking history and were current smokers or had quit within the past 15 years . As with all screening trials , the NLST tested a specific intervention over a finite period . Because initial eligibility extended through age 74 years and participants received 3 annual screening computed tomographic scans , the oldest participants in the trial were aged 77 years . The USPSTF used modeling studies to predict the benefits and harms of screening programs that use different screening intervals , age ranges , smoking histories , and times since quitting . A program that annually screens adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years is projected to have a reasonable balance of benefits and harms . The model assumes that persons who achieve 15 years of smoking cessation during the screening program discontinue screening . This model predicts the outcomes of continuing the screening program used in the NLST through age 80 years . Screening may not be appropriate for patients with substantial comorbid conditions , particularly those at the upper end of the screening age range . The NLST excluded persons who were unlikely to complete curative lung cancer surgery and those with medical conditions that posed a substantial risk for death during the 8-year trial . The baseline characteristics of the NLST showed a relatively healthy sample , and fewer than 10 % of enrolled participants were older than 70 years ( 5 ) . Persons with serious comorbid conditions may experience net harm , no net benefit , or at least substantially less net benefit . Similarly , persons who are unwilling to have curative lung surgery are unlikely to benefit from a screening program . Assessment of Risk Age , total exposure to tobacco smoke , and years since quitting smoking are important risk factors for lung cancer and were used to determine eligibility in the NLST . Other risk factors include specific occupational exposures , radon exposure , family history , and history of pulmonary fibrosis or chronic obstructive lung disease . The incidence of lung cancer is relatively low in persons younger than 50 years but increases with age , especially after age 60 years . In current and former smokers , age-specific incidence rates increase with age and cumulative exposure to tobacco smoke . Smoking cessation substantially reduces a person 's risk for developing and dying of lung cancer . Among persons enrolled in the NLST , those who were at highest risk because of additional risk factors or a greater cumulative exposure to tobacco smoke experienced most of the benefit ( 6 ) . A vali date d multivariate model showed that persons in the highest 60 % of risk accounted for 88 % of all deaths preventable by screening . Screening Tests Low-dose computed tomography has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk persons . Chest radiography and sputum cytologic evaluation have not shown adequate sensitivity or specificity as screening tests . Therefore , LDCT is currently the only recommended screening test for lung cancer . Treatment Surgical resection is the current st and ard of care for localized NSCLC . This type of cancer is treated with surgical resection when possible and also with radiation and chemotherapy . Annual LDCT screening may not be useful for patients with life-limiting comorbid conditions or poor functional status who may not be c and i date s for surgery . Other Approaches to Prevention Smoking cessation is the most important intervention to prevent NSCLC . Advising smokers to stop smoking and preventing nonsmokers from being exposed to tobacco smoke are the most effective ways to decrease the morbidity and mortality associated with lung cancer . Current smokers should be informed of their continuing risk for lung cancer and offered cessation treatments . Screening with LDCT should be viewed as an adjunct to tobacco cessation interventions . Useful Re sources Clinicians have many re sources to help patients stop smoking . The Centers for Disease Control and Prevention has developed a Web site with many such re sources , including information on tobacco quit lines , available in several language s ( www.cdc.gov/tobacco/campaign/tips ) . Quit |
12,475 | 29,581,711 | Conclusions For patients requiring OAC after coronary intervention , OAC plus clopidogrel may bring more clinical net benefit than TT , whereas OAC plus aspirin should be the last choice . | Objective The main aim of this meta- analysis is to compare the efficacy and safety of dual versus single antiplatelet therapy for patients taking oral anticoagulation ( OAC ) after coronary intervention .
Background The optimal regimen remains controversial for patients taking OAC after coronary intervention . | BACKGROUND Patients receiving oral anticoagulation ( OAC ) who undergo drug-eluting stent ( DES ) implantation require additional dual antiplatelet therapy with aspirin and clopidogrel . Such triple therapy confers an elevated bleeding risk , and its optimal duration is not known . OBJECTIVES The goal of this study was to evaluate whether shortening the duration of clopidogrel therapy from 6 months to 6 weeks after DES implantation was associated with a superior net clinical outcome in patients receiving concomitant aspirin and OAC . METHODS In this r and omized , open-label trial , we enrolled patients receiving OAC who underwent DES implantation at 3 European centers between September 2008 and December 2013 . A total of 614 patients receiving concomitant aspirin and OAC were r and omized to either 6-week clopidogrel therapy ( n=307 ) or 6-month clopidogrel therapy ( n=307 ) . The primary endpoint was a composite of death , myocardial infa rct ion ( MI ) , definite stent thrombosis , stroke , or Thrombolysis In Myocardial Infa rct ion ( TIMI ) major bleeding at 9 months . RESULTS The primary endpoint occurred in 30 patients ( 9.8 % ) in the 6-week group compared with 27 patients ( 8.8 % ) in the 6-month group ( hazard ratio [ HR ] : 1.14 ; 95 % CI : 0.68 to 1.91 ; p=0.63 ) . There were no significant differences for the secondary combined ischemic endpoint of cardiac death , MI , definite stent thrombosis , and ischemic stroke ( 12 [ 4.0 % ] vs. 13 [ 4.3 % ] ; HR : 0.93 ; 95 % CI : 0.43 to 2.05 ; p=0.87 ) or the secondary bleeding endpoint of TIMI major bleeding ( 16 [ 5.3 % ] vs. 12 [ 4.0 % ] ; HR : 1.35 ; 95 % CI : 0.64 to 2.84 ; p=0.44 ) . CONCLUSIONS Six weeks of triple therapy was not superior to 6 months with respect to net clinical outcomes . These results suggest that physicians should weigh the trade-off between ischemic and bleeding risk when choosing the shorter or longer duration of triple therapy . ( Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation [ ISAR-TRIPLE ] ; NCT00776633 ) BACKGROUND Oral anticoagulation ( OAC ) is the recommended therapy for patients with atrial fibrillation ( AF ) because it reduces the risk of stroke and other thromboembolic events . Dual antiplatelet therapy ( DAPT ) is required after percutaneous coronary intervention and stenting ( PCI-S ) . In patients with AF requiring PCI-S , the association of DAPT and OAC carries an increased risk of bleeding , whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events . OBJECTIVE The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy ( TT ) in patients with nonvalvular AF at low-to-moderate risk of stroke ( CHADS2 score ≤2 ) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications . DESIGN The MUSICA-2 is a multicenter , open-label r and omized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S. The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events : death , myocardial infa rct ion , stent thrombosis , or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients . CONCLUSIONS The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications Most evidence regarding the efficacy and safety of the antithrombotic regimens for patients with atrial fibrillation ( AF ) undergoing percutaneous coronary intervention with stent ( PCI‐S ) derives from small , single‐center , retrospective data sets . To obtain further data on this issue , we carried out the prospect i ve , multicenter , observational Management of patients with Atrial Fibrillation undergoing Coronary Artery Stenting ( AFCAS ) registry ( Clinical trials.gov identifier NCT00596570 ) Background Chronic atrial fibrillation ( AF ) , coexisting with a history of recent coronary angioplasty with stent ( PCI-S ) , represents an encoded indication for oral anticoagulation ( OAC ) with warfarin plus dual antiplatelet therapy ( DAPT ) . Methods Using a retrospective cohort study , we determined the respective impacts on cardiovascular outcomes of three different pharmacologic regimens , i.e. , triple therapy ( TT ) with warfarin + clopidogrel and aspirin , dual therapy ( DT ) with warfarin + clopidogrel or aspirin , and DAPT with clopidogrel + aspirin . Outcomes of interest were all-cause mortality , ischemic cardiac events , ischemic cerebral events , and bleeding events . The inclusion criterion was the coexistence of an indication for OAC ( e.g. , chronic AF ) with an indication for DAPT due to recent PCI-S. Results Among the 98 patients enrolled , 48 ( 49 % ) , 31 ( 31.6 % ) , and 19 ( 19.4 % ) patients were prescribed TT , DT , and DAPT , respectively . Throughout a mean follow-up of 378 ± 15.7 days , there were no significant differences between the three regimens for all abovementioned outcomes . In particular , the total frequency of major bleeding was similar in the three groups : five cases ( 10.4 % ) in TT , one case ( 3.22 % ) in DT and no case in DAPT groups ( Chi-square test , P = 0.1987 ) . Conclusions TT , DT and DAPT displayed similar efficacy and safety . Although the superiority of OAC vs. DAPT for stroke prevention in AF patients has been demonstrated by previous r and omized trials , a smaller frequency of high thromboembolic risks ’ features in DAPT group of the present study may have prevented the observation of a higher incidence of ischemic stroke in this group BACKGROUND The effects of dual antiplatelet therapy ( DAPT ) and triple therapy ( TT : DAPT plus oral anticoagulation ) in patients with atrial fibrillation ( AF ) undergoing percutaneous coronary intervention ( PCI ) regarding to CHA2DS2-VASc score remain undefined . We compare the effect of TT vs. DAPT in this setting regarding the CHA2DS2-VASc score . METHODS AND RESULTS In a prospect i ve multicenter registry , 585 patients ( 75.2 % male , 73.2 ± 8.2 years ) with AF undergoing PCI were followed up during 1 year . Of them , 157 ( 26.8 % ) had a CHA2DS2-VASc=1 , and 428 ( 73.2 % ) had a CHA2DS2-VASc ≥2 . TT was prescribed in 51.6 % with CHA2DS2-VASc=1 and in 55.5 % with CHA2DS2-VASc ≥ 2 . Patients with CHA2DS2-VASc=1 receiving TT had a similar thromboembolism rate to those on DAPT ( 1.2 % vs. 1.3 % , P=0.73 ) , but more total ( 19.5 % vs. 6.9 % , P=0.01 ) and a tendency to more major ( 4.9 % vs. 0 % , P=0.06 ) bleeding . However , patients with CHA2DS2-VASc ≥ 2 receiving TT had a lower thromboembolism rate ( 1.7 % vs. 5.3 % , P=0.03 ) and a trend towards more bleeds ( 21.8 % vs. 15.6 % , P=0.06 ) , with an excess of major bleeding ( 8.4 % vs. 3.1 % , P=0.01 ) . Rates of major adverse cardiac events ( MACE ) in both CHA2DS2-VASc subgroups were similar , irrespective of treatment . In a Cox multivariate analysis , TT was associated to major bleeding , but not with MACE . CONCLUSIONS In patients with AF and CHA2DS2-VASc=1 undergoing PCI , the use of TT involves a high risk of bleeding without a significant benefit in preventing thromboembolism Objectives : To identify the therapeutic regimens used at discharge in patients receiving oral anticoagulant therapy ( OAT ) who undergo stenting percutaneous coronary intervention and stent implantation ( PCI-S ) , and to assess the safety and efficacy associated with different therapeutic regimens according to thromboembolic risk . Design : A prospect i ve multicentre registry . Setting : In hospital , after discharge and follow-up by telephone call . Patients and methods : 405 patients ( 328 male/77 female ; mean ( SD ) age 71 ( 9 ) years ) receiving OAT who underwent PCI-S between November 2003 and June 2006 from nine catheterisation laboratories of tertiary care teaching hospitals in Spain and one in the United Kingdom were included . Results : Three therapeutic regimens were identified at discharge : triple therapy (TT)—that is , any anticoagulant ( AC ) plus double antiplatelet therapy ( DAT ; 278 patients ( 68.6 % ) ; AC and a single antiplatelet ( AC+AT ; 46 ( 11.4 % ) ) and DAT only ( 81 ( 20 % ) ) . At 6 months , patients receiving TT showed the greatest rate of bleeding events . No patients receiving DAT at low thromboembolic risk presented a bleeding event ( 14.8 % receiving TT , 11.8 % receiving AC+AT and 0 % receiving DAT , p = 0.033 ) or cardiovascular event ( 6.7 % receiving TT , 0 % receiving AC+AT and 0 % receiving DAT , p = 0.126 ) . The combination of AC+AT showed the worst rate of adverse events in the whole cohort , especially in patients at moderate – high thromboembolic risk . Conclusions : In patients receiving OAT , TT was the most commonly used regimen after PCI-S. DAT was associated with the lowest rate of bleeding events and a similar efficacy to TT in patients at low thromboembolic risk . TT should probably be restricted to patients at moderate – high thromboembolic risk BACKGROUND The optimal antithrombotic strategy for patients with atrial fibrillation ( AF ) undergoing drug-eluting stent ( DES ) implantation is unknown . METHODS AND RESULTS The 622 consecutive AF patients undergoing DES implantation were prospect ively enrolled . Among them , 142 patients ( TT group ) continued triple antithrombotic therapy comprising aspirin , clopidogrel and warfarin after discharge ; 355 patients ( DT group ) had dual antiplatelet therapy ; 125 patients ( WS group ) were discharged with warfarin and a single antiplatelet agent . Target INR was set as 1.8 - 2.5 and was regularly monitored after discharge . The TT group had a significant reduction in stroke and major adverse cardiac and cerebral events ( MACCE ) ( 8.8 % vs 20.1 % vs 14.9 % , P=0.010 ) as compared with either the DT or WS group . In the Cox regression analysis , administration with warfarin ( hazard ratio ( HR ) 0.49 ; 95 % confidence interval ( CI ) 0.31 - 0.77 ; P=0.002 ) and baseline CHADS(2 ) score > or=2 ( HR 2.09 ; 95%CI 1.27 - 3.45 ; P=0.004 ) were independent predictors of MACCE . Importantly , the incidence of major bleeding was comparable among 3 groups ( 2.9 % vs 1.8 % vs 2.5 % , P=0.725 ) , although the overall bleeding rate was increased in the TT group . Kaplan-Meier analysis indicated that the TT group was associated with the best net clinical outcome . CONCLUSIONS The cardiovascular benefits of triple antithrombotic therapy were confirmed by reducing the MACCE rate , and its major bleeding risk might be acceptable if the INR is closely monitored Current recommendations for the antithrombotic management of patients receiving oral anticoagulation ( OAC ) who undergo percutaneous coronary intervention with stent implantation ( PCI-S ) are based on limited and relatively weak data . To broaden and strengthen available evidence , the management and 1-year outcomes of OAC patients who underwent PCI-S and were included in a prospect i ve , multicenter registry from 2003 to 2007 were evaluated . Among the 632 patients receiving OAC , mostly because of atrial fibrillation ( 58 % ) , who underwent PCI-S , mostly because of acute coronary syndromes ( 63 % ) , dual-antiplatelet therapy with aspirin and clopidogrel was the most frequently prescribed at discharge ( 48 % ) , followed by triple therapy with OAC , aspirin , and clopidogrel ( 32 % ) and OAC plus aspirin ( 18 % ) . The choice of antithrombotic therapy largely matched the thromboembolic risk profiles of patients , with the prescription of regimens including OAC predicted by the presence of non-low-risk features . The cumulative 1-year occurrence of major adverse cardiovascular events was as high as 27 % and was not significantly different among the 3 treatment groups . Stroke and stent thrombosis were limited to 2 % and 3 % , respectively , and although no significant differences were found among the 3 groups , stroke was 4 times less frequent when OAC , with either 1 or 2 antiplatelet agents , was administered . Major bleeding was also limited to 3 % , with no significant differences among the 3 groups . In conclusion , these findings suggest overall real-world management of OAC patients who undergo PCI-S that is in accordance with their clinical risk profiles and give further support to the reported efficacy and safety of triple therapy for the optimal treatment of these patients AIMS To compare dual vs. triple antiplatelet pre-treatment in patients with non-ST-elevation acute coronary syndrome ( NSTE ACS ) who were planned for early catheterization . METHODS AND RESULTS A total of 328 consecutive patients with NSTE ACS were included and were r and omized to pre-treatment with dual ( n = 166 , aspirin , clopidogrel 600 mg ) or triple antiplatelet therapy ( n = 162 , aspirin , clopidogrel 300 mg , and Tirofiban ) . The primary endpoint was enzymatic infa rct size , defined as cumulative LDH release ( LDHQ(48 ) ) . Initial TIMI flow of the culprit vessel was a pre-specified secondary endpoint . Angiography was performed in 98 % of patients at a median of 23 h after admission . Enzymatic infa rct size ( median , 25 - 75 % ) was 166 ( 60 - 349 ) IU/L in the triple group compared with 193 ( 75 - 466 ) IU/L in the dual group ( P = 0.2 ) . Initial TIMI 3 flow of the culprit vessel was significantly more often observed after triple antiplatelet therapy ( 67 vs. 47 % , P = 0.002 ) . At 30 days follow-up , myocardial infa rct ion ( MI ) occurred in 46 % of patients in the triple antiplatelet group , compared with 57 % in the dual antiplatelet group , P = 0.052 . No significant difference in bleeding was present . CONCLUSION This study showed that in patients with NSTE ACS , triple antiplatelet pre-treatment was associated with a non-significant reduction in enzymatic infa rct size , a significantly better initial perfusion of the culprit vessel , and a trend towards a better survival without death or MI . Further , large-scale studies should be performed to find whether the beneficial trend in favour of triple antiplatelet pre-treatment can be reproduced Associations between atrial fibrillation ( AF ) , outcomes , and response to antiplatelet therapies in patients with acute coronary syndrome ( ACS ) managed medically without revascularization remain uncertain . We examined these associations for medically managed ACS patients r and omized to dual antiplatelet therapy ( DAPT ) using patient data from the TRILOGY ACS trial . DAPT included aspirin plus clopidogrel 75 mg/d or prasugrel 10 mg/d ( 5 mg/d for those < 60 kg or age ≥75 years ) . Patients receiving oral anticoagulants were excluded . Cox proportional hazards regression modeling was used to characterize associations between patients with AF ( AF+ ) vs those without ( AF− ) and risk of ischemic and bleeding events , and to explore effects of r and omized treatment on outcomes . Among 9101 patients with baseline AF status , 710 ( 7.8 % ) had AF . AF+ patients were older and had more comorbidities . Unadjusted associations of the composite of cardiovascular death/myocardial infa rct ion/stroke were significantly higher among AF patients at 30 months ( 31.1 % vs 18.4 % ; HR : 1.61 , 95 % CI : 1.35‐1.92 , P < 0.001 ) , but differences did not persist after adjustment ( HR : 1.16 , 95 % CI : 0.97‐1.39 , P = 0.11 ) . When individual components of the composite endpoint were evaluated , 30‐month risk of events in AF+ patients was significantly higher . Thirty‐month risk of all‐cause death was significantly higher in AF+ patients : 18.1 % vs 11.1 % ( HR : 1.62 , 95 % CI : 1.30‐2.02 , P < 0.001 ) . There was no significant interaction with r and omized treatment and AF for the primary endpoint . Among medically managed high‐risk ACS patients receiving DAPT , AF was associated with higher unadjusted risks of ischemic and bleeding outcomes that were similar by treatment group BACKGROUND Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation . However , long-term monitoring is necessary and many patients can not achieve optimum anticoagulation . We assessed whether clopidogrel plus aspirin was non-inferior to oral anticoagulation therapy for prevention of vascular events . METHODS Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke , and were r and omly allocated to receive oral anticoagulation therapy ( target international normalised ratio of 2.0 - 3.0 ; n=3371 ) or clopidogrel ( 75 mg per day ) plus aspirin ( 75 - 100 mg per day recommended ; n=3335 ) . Outcome events were adjudicated by a blinded committee . Primary outcome was first occurrence of stroke , non-CNS systemic embolus , myocardial infa rct ion , or vascular death . Analyses were by intention-to-treat . This study is registered with Clinical Trials.gov , number NCT00243178 . RESULTS The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy . There were 165 primary events in patients on oral anticoagulation therapy ( annual risk 3.93 % ) and 234 in those on clopidogrel plus aspirin ( annual risk 5.60 % ; relative risk 1.44 ( 1.18 - 1.76 ; p=0.0003 ) . Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events ( relative risk 1.50 , 95 % CI 1.19 - 1.89 ) and a significantly ( p=0.03 for interaction ) lower risk of major bleeding with oral anticoagulation therapy ( 1.30 ; 0.94 - 1.79 ) than patients not on this treatment at study entry ( 1.27 , 0.85 - 1.89 and 0.59 , 0.32 - 1.08 , respectively ) . CONCLUSION Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke , especially in those already taking oral anticoagulation therapy BACKGROUND In patients with atrial fibrillation undergoing percutaneous coronary intervention ( PCI ) with placement of stents , st and ard anticoagulation with a vitamin K antagonist plus dual antiplatelet therapy ( DAPT ) with a P2Y12 inhibitor and aspirin reduces the risk of thrombosis and stroke but increases the risk of bleeding . The effectiveness and safety of anticoagulation with rivaroxaban plus either one or two antiplatelet agents are uncertain . METHODS We r and omly assigned 2124 participants with nonvalvular atrial fibrillation who had undergone PCI with stenting to receive , in a 1:1:1 ratio , low-dose rivaroxaban ( 15 mg once daily ) plus a P2Y12 inhibitor for 12 months ( group 1 ) , very-low-dose rivaroxaban ( 2.5 mg twice daily ) plus DAPT for 1 , 6 , or 12 months ( group 2 ) , or st and ard therapy with a dose-adjusted vitamin K antagonist ( once daily ) plus DAPT for 1 , 6 , or 12 months ( group 3 ) . The primary safety outcome was clinical ly significant bleeding ( a composite of major bleeding or minor bleeding according to Thrombolysis in Myocardial Infa rct ion [ TIMI ] criteria or bleeding requiring medical attention ) . RESULTS The rates of clinical ly significant bleeding were lower in the two groups receiving rivaroxaban than in the group receiving st and ard therapy ( 16.8 % in group 1 , 18.0 % in group 2 , and 26.7 % in group 3 ; hazard ratio for group 1 vs. group 3 , 0.59 ; 95 % confidence interval [ CI ] , 0.47 to 0.76 ; P<0.001 ; hazard ratio for group 2 vs. group 3 , 0.63 ; 95 % CI , 0.50 to 0.80 ; P<0.001 ) . The rates of death from cardiovascular causes , myocardial infa rct ion , or stroke were similar in the three groups ( Kaplan-Meier estimates , 6.5 % in group 1 , 5.6 % in group 2 , and 6.0 % in group 3 ; P values for all comparisons were nonsignificant ) . CONCLUSIONS In participants with atrial fibrillation undergoing PCI with placement of stents , the administration of either low-dose rivaroxaban plus a P2Y12 inhibitor for 12 months or very-low-dose rivaroxaban plus DAPT for 1 , 6 , or 12 months was associated with a lower rate of clinical ly significant bleeding than was st and ard therapy with a vitamin K antagonist plus DAPT for 1 , 6 , or 12 months . The three groups had similar efficacy rates , although the observed broad confidence intervals diminish the surety of any conclusions regarding efficacy . ( Funded by Janssen Scientific Affairs and Bayer Pharmaceuticals ; PIONEER AF-PCI Clinical Trials.gov number , NCT01830543 . ) |
12,476 | 20,472,696 | These were whether or not the subject of smoking is broached by a health professional , the content of advice and information provided , the manner of communication , having service protocol s , follow-up discussion , staff confidence in their skills , the impact of time and re source constraints , staff perceptions of ineffectiveness , differences between professionals , and obstacles to accessing interventions .
DISCUSSION The findings suggest variation in practice between services and different professional groups , in particular regarding the recommendation of quitting smoking versus cutting down but also in regard to procedural aspects , such as recording status and repeat advice giving .
These differences offer the potential for a pregnant woman to receive contradicting advice . | INTRODUCTION The review had the aim of investigating factors enabling or discouraging the uptake of smoking cessation services by pregnant women smokers . | OBJECTIVE To assess Ohio obstetrician/gynecologists ' perceptions and use of the 5As method of smoking cessation ( ask , advise , assess , assist , and arrange ) with pregnant patients who smoke . METHODS A three-wave mailing procedure was used with a statewide r and om sample of obstetrician/ gynecologists who responded to a valid and reliable 31-item question naire . RESULTS Regarding the 5As method of smoking cessation , almost all ( 98 % ) asked their pregnant patients about smoking , but fewer respondents engaged in advising ( 66 % ) , assessing ( 42 % ) , assisting ( 29 % ) , and arranging for follow-up visits or referrals ( 6 % ) . Higher efficacy expectations were associated with greater use of the 5As method ( r = 0.52 , p < 0.001 ) . A majority believed that two cessation activities would result in smoking cessation in pregnant smokers : explaining the dangers of smoking ( 65 % ) and referring pregnant smokers to smoking cessation programs ( 57 % ) . However , 26 % of physicians reported that they were " slightly confident " or " not confident at all " in their ability to refer pregnant smokers to such programs , and 6 % of physicians reported always providing smoking cessation referrals . A significant proportion of respondents believed that prenatal smoking would not cause severe effects for the unborn child but would likely lead to moderate ( 46 % ) or minor ( 3 % ) health effects . CONCLUSION Obstetrician/gynecologists face many competing dem and s for their time and energy , yet 62 % believed smoking cessation advice would be of significant value . Physicians with higher levels of efficacy expectations reported significantly greater use of the 5 As . Future research should explore ways to facilitate obstetrician/gynecologists ' use of the 5As method OBJECTIVE To compare the implementation , delivery , and implication s for dissemination of 2 different maternal smoking-cessation/relapse-prevention interventions in managed care environments . STUDY DESIGN Healthy Options for Pregnancy and Parenting ( HOPP ) was a r and omized , controlled efficacy trial of an intervention that bypassed the clinical setting . Stop Tobacco for OuR Kids ( STORK ) was a quasi-experimental effectiveness study of a point-of-service intervention . Both incorporated prenatal and postnatal components . PATIENTS AND METHODS Subjects in both studies were pregnant women who either smoked currently or had quit recently . The major intervention in HOPP was telephone counseling delivered by trained counselors , whereas the STORK intervention was delivered by providers and staff during prepartum , inpatient postpartum , and well-baby visits . RESULTS In HOPP , 97 % of telephone intervention participants reported receiving 1 or more counselor calls . The intervention delayed but did not prevent postpartum relapse to smoking . Problems with intervention delivery related primarily to identification of the target population and acceptance of repeated calls . STORK delivered 1 or more cessation contacts to 91 % of prenatal smokers in year 1 , but the rate of intervention delivery declined in years 2 and 3 . Modest differences were obtained in sustained abstinence between 6 and 12 months postpartum , but not in point prevalence abstinence at 12 months . CONCLUSIONS The projects were compared using 4 of the 5 dimensions of the RE- AIM model including reach , adoption , implementation , and maintenance . It was difficult to apply the fifth dimension , efficacy , because of the differences in study design and purpose of the interventions . The strengths and limitations of each project were identified , and it was concluded that a combined intervention that incorporates elements of both HOPP and STORK would be optimal if it could be implemented at reasonable cost Antenatal clinic staff were surveyed for their attitudes to smoking in pregnancy in 1993 and again in 1996 to monitor the effect of a r and omised controlled trial of a smoking intervention conducted in the clinic over the period . Descriptive analysis showed that staff believe smoking in pregnancy is an important health risk for both mother and baby , quitting smoking is difficult , counselling is only moderately successful , they lack the skill to counsel smokers and there is little time to do so . The lack of structural support within clinic administration , the lack of a comprehensive hospital policy on smoking and unclear public health messages , were also identified as barriers to reducing the prevalence of smoking This study investigated the impact of a behaviorally based intervention design ed to increase the number of hospitals that routinely provide effective smoking cessation programs for pregnant women . In Queensl and , Australia , 70 publicly funded hospitals were matched on numbers of births and maternal socioeconomic status and r and omly allocated to an awareness-only intervention group or a behaviorally based intervention group . Success was defined as the routine offer of an evidence -based smoking cessation program to at least 80 % of the pregnant clients who smoke . At 1 month , 65 % of the behaviorally based intervention hospitals agreed to provide material s about smoking cessation programs for their antenatal patients , compared with 3 % of the awarenessonly hospitals . After 1 year , 43 % of the intervention hospitals still provided the material , compared with 9 % of the awareness-only hospitals . These findings showthat a brief intervention to hospitals can encourage antenatal staff to provide smoking cessation material s to pregnant women Background African American women are at increased risk for poor pregnancy outcomes compared to other racial-ethnic groups . Single or multiple psychosocial and behavioral factors may contribute to this risk . Most interventions focus on singular risks . This paper describes the design , implementation , challenges faced , and acceptability of a behavioral counseling intervention for low income , pregnant African American women which integrated multiple targeted risks into a multi-component format . Methods Six academic institutions in Washington , DC collaborated in the development of a community-wide , primary care research study , DC-HOPE , to improve pregnancy outcomes . Cigarette smoking , environmental tobacco smoke exposure , depression and intimate partner violence were the four risks targeted because of their adverse impact on pregnancy . Evidence -based models for addressing each risk were adapted and integrated into a multiple risk behavior intervention format . Pregnant women attending six urban prenatal clinics were screened for eligibility and risks and r and omized to intervention or usual care . The 10-session intervention was delivered in conjunction with prenatal and postpartum care visits . Descriptive statistics on risk factor distributions , intervention attendance and length ( i.e. , with < 4 sessions considered minimal adherence ) for all enrolled women ( n = 1,044 ) , and perceptions of study participation from a sub- sample of those enrolled ( n = 152 ) are reported . Results Forty-eight percent of women screened were eligible based on presence of targeted risks , 76 % of those eligible were enrolled , and 79 % of those enrolled were retained postpartum . Most women reported a single risk factor ( 61 % ) ; 39 % had multiple risks . Eighty-four percent of intervention women attended at least one session ( 60 % attended ≥ 4 sessions ) without disruption of clinic scheduling . Specific risk factor content was delivered as prescribed in 80 % or more of the sessions ; 78 % of sessions were fully completed ( where all required risk content was covered ) . Ninety-three percent of the sub sample of intervention women had a positive view of their relationship with their counselor . Most intervention women found the session content helpful . Implementation challenges of addressing multiple risk behaviors are discussed . Conclusion While implementation adjustments and flexibility are necessary , multiple risk behavioral interventions can be implemented in a prenatal care setting without significant disruption of services , and with a majority of referred African American women participating in and expressing satisfaction with treatment sessions OBJECTIVE To explore the midwife 's role in providing education and support for changes in smoking behaviour during usual primary maternity care . DESIGN A qualitative study using a thematic approach to analysis of data collected in face-to-face interviews . SETTING AND PARTICIPANTS Eleven women who had participated in the intervention groups of the MEWS Study , a cluster r and omised trial of education and support for women who smoke , and 16 midwives from the intervention and control arms of the trial . The trial was set in the lower North Isl and of New Zeal and in 2000 . FINDINGS Midwives acknowledged that asking women about smoking was part of their role as maternity care providers . However , many found it difficult to know how to ask women about their smoking , how to identify the women who would be receptive to advice and how to support them to make changes to their smoking . Midwives were also concerned about making women feel guiltier than they already did about their smoking , and about the impact of providing smoking cessation on their relationship with women . In contrast , women expected their midwife to ask them about their smoking . When women wanted to quit their midwife was an extremely valuable source of information and support . Midwives were also in a position to help women who did not want to quit to make other changes to their smoking behaviour . Even women who did not want to quit were prepared to be asked about their smoking . Problems arose when the way the midwife asked and the frequency of her enquiries were not appropriate for the stage of the change cycle the woman was in . IMPLICATION S FOR PRACTICE Midwives can effectively provide education and support for smoking change during pregnancy if they match the woman 's readiness to make changes with the type of advice and support they provide |
12,477 | 17,344,246 | The overall risk of MI with NSAIDs and cyclo-oxygenase-2-specific drugs was small ; rofecoxib showed the highest risk .
There was an increased MI risk with cyclo-oxygenase-2-specific drugs compared with NSAIDs , but less serious upper gastrointestinal toxicity | OBJECTIVE The comparative risk of myocardial infa rct ion ( MI ) with cyclo-oxygenase-2-specific drugs and traditional non-steroidal anti-inflammatory drugs ( NSAIDs ) was determined . | BACKGROUND Bodily pain and physical disability can negatively impact health-related quality of life ( HRQL ) in patients with osteoarthritis ( OA ) . OBJECTIVE To assess the effects of treatment with a new agent , rofecoxib , on HRQL in patients with OA . STUDY DESIGN R and omized , double-blind , 6-week clinical trial comparing treatment with rofecoxib , 5 to 50 mg , with placebo in 672 patients with OA of the hip or knee . MAIN OUTCOME MEASURE Patient HRQL was assessed at baseline and at the end of treatment using the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) . RESULTS At 6 weeks , mean change from baseline in all SF-36 mental and physical health domain scores demonstrated significant improvement with rofecoxib use ( P < .05 for all doses for all SF-36 domains ) , with evidence of a dose-response relation . Improvements in mental and physical HRQL domains with rofecoxib treatment were significantly greater than those with placebo treatment ( P < .05 for each dose of rofecoxib vs placebo for all domains except general health ) and highly correlated with improvements observed using disease-specific OA outcome measures such as the Western Ontario and McMaster Universities Osteoarthritis Index-visual Analog 3.0 OA index pain and physical function subscales . The effect of rofecoxib vs placebo treatment on mental health largely disappeared after adjustment for improvement in OA disease-specific measures . CONCLUSIONS Rofecoxib treatment increased physical and mental HRQL domain scores on the SF-36 . Improvements in mental health with rofecoxib use primarily result ed from effective treatment of OA ( i.e. , reduction in pain and improvement in physical function ) BACKGROUND Acetaminophen ( paracetamol ) is recommended as the initial pharmacological treatment for knee or hip osteoarthritis . However , survey and clinical trial data indicate greater efficacy for non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 specific inhibitors . DESIGN Two r and omised , double blind , placebo controlled , crossover multicentre clinical trials , Patient Preference for Placebo , Acetaminophen or Celecoxib Efficacy Studies ( PACES ) . PATIENTS Osteoarthritis of knee or hip . INTERVENTION " Wash out " of treatment ; r and omisation ; 6 weeks of celecoxib 200 mg/day , acetaminophen 1000 mg four times a day , or placebo ; second " wash out ; " crossover to 6 weeks of second treatment . MEASUREMENTS Western Ontario McMaster Osteoarthritis Index ( WOMAC ) , visual analogue pain scale , patient preference between two treatments . RESULTS Celecoxib was more efficacious than acetaminophen in both periods in both studies ; WOMAC and pain scale scores differed at p<0.05 in period II and both periods combined of PACES-a and in periods I and II and both periods combined in PACES-b , but not in period I of PACES-a . Acetaminophen was more efficacious than placebo , generally p<0.05 in PACES-b , and > 0.05 in PACES-a . Patient preferences were 53 % celecoxib v 24 % acetaminophen in PACES-a ( p<0.001 ) and 50 % v 32 % in PACES-b ( p = 0.009 ) ; 37 % acetaminophen v 28 % placebo in PACES-a ( p = 0.340 ) and 48 % v 24 % in PACES-b ( p = 0.007 ) . No clinical ly or statistically significant differences were seen in adverse events or tolerability among the three treatment groups . CONCLUSIONS Greater efficacy was seen for celecoxib v acetaminophen v placebo , while adverse events and tolerability were similar . Variation in results and statistical significance in the two different trials are of interest Background — Although r and omized trials of cyclooxygenase-2 ( COX-2 ) inhibitors have shown increased cardiovascular risk , studies of nonselective , nonsteroidal antiinflammatory drugs ( NSAIDs ) and acetaminophen have been inconsistent . Methods and Results — We examined the influence of NSAIDs and acetaminophen on the risk of major cardiovascular events ( nonfatal myocardial infa rct ion , fatal coronary heart disease , nonfatal and fatal stroke ) in a prospect i ve cohort of 70 971 women , aged 44 to 69 years at baseline , free of known cardiovascular disease or cancer , who provided medication data biennially since 1990 . During 12 years of follow-up , we confirmed 2041 major cardiovascular events . Women who reported occasional ( 1 to 21 d/mo ) use of NSAIDs or acetaminophen did not experience a significant increase in the risk of cardiovascular events . However , after adjustment for cardiovascular risk factors , women who frequently ( ≥22 d/mo ) used NSAIDs had a relative risk ( RR ) for a cardiovascular event of 1.44 ( 95 % CI , 1.27 to 1.65 ) compared with nonusers , whereas those who frequently consumed acetaminophen had a RR of 1.35 ( 95 % CI , 1.14 to 1.59 ) . The elevated risk associated with frequent NSAID use was particularly evident among current smokers ( RR=1.82 ; 95 % CI , 1.38 to 2.42 ) and was absent among never smokers ( Pinteraction=0.02 ) . Moreover , we observed significant dose-response relations : Compared with nonusers , the RRs for a cardiovascular event among women who used ≥15 tablets per week were 1.86 ( 95 % CI , 1.27 to 2.73 ) for NSAIDs and 1.68 ( 95 % CI , 1.10 to 2.58 ) for acetaminophen . Conclusions — Use of NSAIDs or acetaminophen at high frequency or dose is associated with a significantly increased risk for major cardiovascular events , although more moderate use did not confer substantial risk OBJECTIVE This multicentre , r and omized , double-blind , placebo-controlled parallel-group study was undertaken to investigate the efficacy , safety and tolerability of lumiracoxib ( Prexige ) , a cyclooxygenase-2 selective inhibitor , in patients with primary osteoarthritis ( OA ) of the h and . METHODS The study r and omized 594 patients aged > or = 18 years with symptomatic OA of the h and . Patients underwent a 3 to 7-day washout for previous nonsteroidal anti-inflammatory drugs and those with pain intensity > or = 40 mm on a 100 mm Visual Analogue Scale ( VAS ) in the target h and during the 24 hours prior to baseline and an increase in pain intensity of either > or = 20 % or > or = 10 mm VAS since screening ( whichever was greater ) were r and omized to lumiracoxib 200 mg once daily ( od ) ( n=205 ) , lumiracoxib 400 mg od ( n=193 ) or placebo ( n=196 ) . The primary efficacy variable was overall OA pain intensity ( VAS mm ) in the target h and after 4 weeks of treatment . Safety and tolerability assessment s were performed . RESULTS After 4 weeks of treatment , overall OA pain intensity in the target h and was significantly lower for patients treated with lumiracoxib compared with patients treated with placebo ( both doses p<0.001 ) . There was no significant difference between lumiracoxib doses in terms of the reduction in overall OA pain intensity . Lumiracoxib was well tolerated . The incidence of adverse events was similar for active treatment groups and placebo . CONCLUSIONS Lumiracoxib 200 and 400 mg od were effective and well tolerated treatments for OA of the h and . Lumiracoxib significantly improved overall OA pain intensity in the target h and versus placebo , with a tolerability profile similar to placebo Background Etoricoxib is a highly selective COX-2 inhibitor which was evaluated for the treatment of rheumatoid arthritis ( RA ) . Methods Double-blind , r and omized , placebo and active comparator-controlled , 12-week study conducted at 67 sites in 28 countries . Eligible patients were chronic NSAID users who demonstrated a clinical worsening of arthritis upon withdrawal of pre study NSAIDs . Patients received either placebo , etoricoxib 90 mg once daily , or naproxen 500 mg twice daily ( 2:2:1 allocation ratio ) . Primary efficacy measures included direct assessment of arthritis by counts of tender and swollen joints , and patient and investigator global assessment s of disease activity . Key secondary measures included the Stanford Health Assessment Question naire , patient global assessment of pain , and the percentage of patients who achieved ACR20 responder criteria response ( a composite of pain , inflammation , function , and global assessment s ) . Tolerability was assessed by adverse events and routine laboratory evaluations . Results 1171 patients were screened , 891 patients were r and omized ( N = 357 for placebo , N = 353 for etoricoxib , and N = 181 for naproxen ) , and 687 completed 12 weeks of treatment ( N = 242 for placebo , N = 294 for etoricoxib , and N = 151 for naproxen ) . Compared with patients receiving placebo , patients receiving etoricoxib and naproxen showed significant improvements in all efficacy endpoints ( p<0.05 ) . Treatment responses were similar between the etoricoxib and naproxen groups for all endpoints . The percentage of patients who achieved ACR20 responder criteria response was 41 % in the placebo group , 59 % in the etoricoxib group , and 58 % in the naproxen group . Etoricoxib and naproxen were both generally well tolerated . Conclusions In this study , etoricoxib 90 mg once daily was more effective than placebo and similar in efficacy to naproxen 500 mg twice daily for treating patients with RA over 12 weeks . Etoricoxib 90 mg was generally well tolerated in RA patients SUMMARY Objective : To evaluate and compare the efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis of the knee or hip . Methods : In this 6-week double-blind , active comparator controlled , parallel-group study eligible osteoarthritis patients were r and omised to receive either etoricoxib 60 mg once daily ( n = 256 ) or diclofenac 50 mg three times daily ( n = 260 ) . The primary study endpoint was the Western Ontario McMaster osteoarthritis index ( WOMAC ) pain subscale . Other endpoints included were the WOMAC stiffness and physical function subscales , and the Patient 's Global Assessment of Response to Therapy ( PGART ) question naire . Early efficacy was evaluated using WOMAC first question ( pain walking on a flat surface ) and PGART 4 h after the morning dose of each drug on days 1 and 2 . Rescue medication ( paracetamol ) used was also recorded . The study was design ed to show comparable efficacy between etoricoxib 60 mg once daily and diclofenac 50 mg three times daily with respect to the primary endpoint and was conducted outside the United States at 67 centres in 29 countries . Results : Etoricoxib ( 60 mg once daily ) was comparable in efficacy to diclofenac ( 150 mg daily ) on all the above parameters . The one exception was in the assessment of early efficacy where etoricoxib demonstrated significantly greater benefit within 4 h of taking the first dose on the first day of therapy ( p = 0.007 ) as evaluated by the percentage of patients with good or excellent ( PGART ) responses . The treatment effects of both drugs were similar by the time day 2 was reached and were sustained throughout the 6 weeks of therapy . Both treatments were generally well tolerated . Conclusions : Etoricoxib is clinical ly effective in the therapy of osteoarthritis providing a magnitude of effect comparable to that of the maximum recommended daily dose of diclofenac . The onset of clinical benefit with etoricoxib on day one is more rapid than that of diclofenac . Both drugs were generally well tolerated OBJECTIVE To compare the efficacy of the cyclooxygenase 2 (COX-2)-specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of osteoarthritis ( OA ) . METHODS In this r and omized , placebo-controlled , double-blind , multicenter study , 475 patients with OA of the knee received either celecoxib 200 mg/day ( n = 189 ) , rofecoxib 25 mg/day ( n = 190 ) , or placebo ( n = 96 ) for 6 weeks . Arthritis assessment s were performed at baseline , week 3 , and week 6 ( or at the time of early termination ) . RESULTS In primary measures of efficacy ( OA pain score on a 100-mm visual analog scale [ VAS ] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index ) , celecoxib 200 mg/day and rofecoxib 25 mg/day demonstrated similar efficacy . At week 6 , celecoxib was associated with a 34-mm mean improvement on the VAS for OA pain , compared with 31.6 mm for rofecoxib and 21.2 mm for placebo . The difference between celecoxib and rofecoxib was -2.5 mm , with an upper limit of the 95 % confidence interval of 2.7 mm and within the prespecified definition of noninferiority . Secondary measures of efficacy showed similar results . All differences in primary and secondary measures of efficacy between the 2 active treatments and placebo were statistically significant ( P < 0.02 ) , whereas all of the comparisons of efficacy between celecoxib and rofecoxib met the predefined criteria for noninferiority . All treatments were well tolerated throughout the study , with similar proportions of patients withdrawing due to adverse events . CONCLUSION Celecoxib 200 mg/day and rofecoxib 25 mg/day are equally efficacious in treating the signs and symptoms of OA BACKGROUND Lumiracoxib is a cyclooxygenase-2-selective inhibitor developed for the treatment of osteoarthritis ( OA ) , rheumatoid arthritis , and acute pain . OBJECTIVES This study assessed the efficacy and tolerability of lumiracoxib 100 mg QD compared with celecoxib and placebo in patients with OA of the knee . METHODS In this 13-week , double-blind , double-dummy , placebo-controlled , parallel-group study , patients with primary OA of the knee and pain intensity in the target knee a 40 mm on a 100-mm visual analog scale after a 3- to 7-day washout of nonsteroidal anti-inflammatory drugs were r and omized to receive lumiracoxib 100 mg QD , lumiracoxib 100 mg QD with a loading dose of lumiracoxib 200 mg QD for the first 2 weeks , celecoxib 200 mg QD , or placebo . Three primary efficacy variables were assessed at the end of the study : pain intensity in the target knee , the patient 's global assessment of disease activity , and functional status ( Western Ontario and McMaster Universities Osteoarthritis Index total score ) . In addition , the treatment response was assessed using the Outcome Measures in Clinical Trials-Osteoarthritis Research Society International ( OMERACT OARSI ) criteria . The safety profile and tolerability of all treatments were also examined . RESULTS The study enrolled 1551 patients ( primarily white ; 62 % female ; mean age , 60.5 years ) : 391 were r and omized to receive lumiracoxib 100 mg QD , 385 lumiracoxib 100 mg QD with a loading dose , 393 celecoxib 200 mg QD , and 382 placebo . Treatment groups were closely balanced at baseline with respect to demographic and disease characteristics . Lumiracoxib was superior to placebo ( P < 0.001 ) and similar to celecoxib on all primary efficacy variables . Reductions in pain intensity in the target knee were similar in the 2 lumiracoxib groups at week 13 ( estimated least square mean difference vs placebo : -6.7 and -8.1 mm for lumiracoxib 100 mg QD and lumiracoxib 100 mg QD with loading dose , respectively ; both , P < 0.001 ) ; with celecoxib , the estimated least square mean difference was -5.7 mm ( P < 0.001 ) . Significant differences compared with placebo were seen in all variables starting at week 2 for all active treatments ( all , P < 0.001 ) . No significant differences were seen between the lumiracoxib groups at any time point . Based on OMERACT OARSI criteria , all active treatments were superior to placebo ( all , P < 0.001 ) . Lumiracoxib and celecoxib were well tolerated , with an incidence of adverse events similar to that with placebo ( 64.7 % lumiracoxib 100 mg QD , 67.0 % lumiracoxib 100 mg QD with loading dose , 58.8 % celecoxib , 58.4 % placebo ) . CONCLUSION In this population of patients with OA of the knee , lumiracoxib 100 mg QD was of similar efficacy to celecoxib 200 mg QD and had similar tolerability to placebo OBJECTIVE Non-steroidal antiinflammatory agents are commonly used to treat pain and inflammation associated with osteoarthritis ( OA ) , but have poor gastrointestinal ( GI ) tolerability . This study compared the efficacy of the COX-2 specific inhibitor valdecoxib with naproxen and placebo , in treating symptomatic OA of the hip . DESIGN This multicenter , r and omized , double-blind 12-week study compared the efficacy and tolerability of single daily doses of valdecoxib 5 mg and 10 mg with placebo or naproxen 500 mg BID . Efficacy was assessed by Patient 's and Physician 's Global Assessment of Arthritis , and the WOMAC ( Western Ontario and McMasters ) OA Individual and Composite Indices . The incidence of adverse events was monitored throughout the study . RESULTS Valdecoxib was clinical ly and statistically superior to placebo for Patient 's and Physician 's Global Assessment of Arthritis and for all WOMAC OA Indices over the 12 week study period ( P < or= 0.05 ) . Valdecoxib 10 mg was similar to naproxen in terms of efficacy , and demonstrated greater numerical improvements compared with valdecoxib 5 mg . Valdecoxib 5 mg and 10 mg demonstrated similar tolerability compared to placebo and a lower incidence of GI-related adverse effects compared with naproxen . CONCLUSIONS Single daily doses of valdecoxib 5 mg and 10 mg were similar to naproxen and superior to placebo , in treating symptomatic OA of the hip . Both doses of valdecoxib were well tolerated and demonstrated improved GI tolerability compared to naproxen BACKGROUND Nonsteroidal anti-inflammatory drugs ( NSAIDs ) inhibit both cyclooxygenase-1 ( COX-1 ) and cyclooxygenase-2 ( COX-2 ) . It is not known whether a specific inhibitor of COX-2 will provide efficacy in osteoarthritis ( OA ) comparable with NSAIDs . Therefore , we compared the efficacy and safety of the rofecoxib , which specifically inhibits COX-2 , with those of the NSAID ibuprofen in patients with OA . OBJECTIVE To compare the clinical efficacy and tolerability of rofecoxib ( 12.5 and 25 mg once daily ) with ibuprofen ( 800 mg 3 times daily ) . METHODS A r and omized , double-blind trial of 809 adults with OA was conducted . Patients with OA in whom the knee or hip was the primary source of pain were r and omized to 1 of 4 treatment groups on demonstration of disease activity : placebo ; rofecoxib , 12.5 or 25 mg once daily ; or ibuprofen , 800 mg 3 times daily . Clinical efficacy and safety were monitored during a 6-week treatment period . RESULTS Both doses of rofecoxib demonstrated efficacy clinical ly comparable with ibuprofen as assessed by 3 primary end points ( pain walking on a flat surface [ Western Ontario and McMaster Universities Osteoarthritis Index ] , patient global assessment of response to therapy , and investigator global assessment of disease status ) according to predefined comparability criteria . Both rofecoxib doses and the ibuprofen dose provided significantly ( P<.001 ) greater efficacy than placebo on all primary end points . Results from secondary end points were consistent with those of the primary end points . All treatments were well tolerated ; the overall incidence rates of clinical adverse experiences were not significantly different ( P>.05 ) among the treatment groups . CONCLUSION Rofecoxib was well tolerated and provided clinical efficacy comparable with a high dose of the NSAID ibuprofen OBJECTIVES To compare the efficacy and safety of lumiracoxib with placebo and celecoxib for osteoarthritis OA in a 13 week , multicentre , r and omised , double blind study . METHODS After a 37 day washout period for nonsteroidal antiinflammatory drugs , 1702 patients with knee OA were r and omised to lumiracoxib 200 or 400 mg once daily od , celecoxib 200 mg od , or placebo 2221 . A visual analogue scale VAS pain intensity > or = 40 mm was required . Primary efficacy variables were OA pain intensity VAS mm in the target knee , patients global assessment of disease activity VAS mm , and WOMAC pain subscale and total scores at 13 weeks . OA pain intensity , patients and physicians global assessment of disease activity , and WOMAC total and all subscale scores were analysed by visit as secondary variables . RESULTS Lumiracoxib showed significant improvements in all primary and secondary variables compared with placebo . Lumiracoxib 200 mg od and celecoxib 200 mg od achieved similar improvements in OA pain intensity and functional status . Lumiracoxib 400 mg od demonstrated better efficacy for OA pain intensity and patients global assessment of disease activity at weeks 2 , 4 , and 8 and similar efficacy at week 13 compared with celecoxib 200 mg od . The incidence of adverse events AEs , serious AEs , and discontinuations due to AEs was similar in each group . CONCLUSION Lumiracoxib demonstrated significant improvement in OA pain intensity , patients global assessment of disease activity , and the WOMAC pain subscale and total scores compared with placebo . Lumiracoxib was well tolerated in this study , with overall tolerability similar to that of placebo and celecoxib BACKGROUND Although aspirin has been shown to protect patients from acute myocardial infa rct ion ( AMI ) , the effect of nonaspirin nonsteroidal anti-inflammatory drugs ( NSAIDs ) is not clear . OBJECTIVE To determine whether NSAIDs have a similar effect or whether they differ in their effect on the risk of AMI . METHODS We performed a case-control study of AMI in a large health care data base containing information on all filled prescriptions , hospitalizations , diagnoses , and procedures for all patients covered by the New Jersey Medicaid or Medicare and Pharmaceutical Assistance for the Aged and Disabled programs . We identified 4425 patients hospitalized for AMI between January 1 , 1991 , and December 31 , 1995 , and 17 700 control subjects . Multivariate models were constructed to control for potential confounders . RESULTS A quarter of the cases and controls had filled a prescription for an NSAID in the 6 months before theirAMI ( cases ) or a r and omly assigned index date ( controls ) ; 9 % had filled a prescription for an NSAID that overlapped with their date of AMI or index date . Overall , NSAID users had the same risk of AMI as nonusers , whether such use was measured on the index date ( adjusted odds ratio , 1.04 ; 95 % confidence interval , 0.92 - 1.18 ; P = .55 ) or at any time in the prior 6 months ( adjusted odds ratio , 1.00 ; 95 % confidence interval , 0.92 - 1.08 ; P = .92 ) . However , use of naproxen was associated with a significant reduction in the risk of AMI ( adjusted odds ratio , 0.84 ; 95 % confidence interval , 0.72 - 0.98 ; P = .03 ) . CONCLUSIONS Although NSAIDs have anti-inflammatory and antiplatelet effects similar to those of aspirin , we did not find that these drugs confer a protective effect against AMI . However , use of one specific NSAID , naproxen , appeared to be associated with a reduced rate of AMI , an effect recently suggested by a large r and omized controlled trial as well BACKGROUND Selective inhibition of cyclooxygenase-2 ( COX-2 ) may be associated with an increased risk of thrombotic events , but only limited long-term data have been available for analysis . We report on the cardiovascular outcomes associated with the use of the selective COX-2 inhibitor rofecoxib in a long-term , multicenter , r and omized , placebo-controlled , double-blind trial design ed to determine the effect of three years of treatment with rofecoxib on the risk of recurrent neoplastic polyps of the large bowel in patients with a history of colorectal adenomas . METHODS A total of 2586 patients with a history of colorectal adenomas underwent r and omization : 1287 were assigned to receive 25 mg of rofecoxib daily , and 1299 to receive placebo . All investigator-reported serious adverse events that represented potential thrombotic cardiovascular events were adjudicated in a blinded fashion by an external committee . RESULTS A total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3059 patient-years of follow-up ( 1.50 events per 100 patient-years ) , as compared with 26 patients in the placebo group during 3327 patient-years of follow-up ( 0.78 event per 100 patient-years ) ; the corresponding relative risk was 1.92 ( 95 percent confidence interval , 1.19 to 3.11 ; P=0.008 ) . The increased relative risk became apparent after 18 months of treatment ; during the first 18 months , the event rates were similar in the two groups . The results primarily reflect a greater number of myocardial infa rct ions and ischemic cerebrovascular events in the rofecoxib group . There was earlier separation ( at approximately five months ) between groups in the incidence of nonadjudicated investigator-reported congestive heart failure , pulmonary edema , or cardiac failure ( hazard ratio for the comparison of the rofecoxib group with the placebo group , 4.61 ; 95 percent confidence interval , 1.50 to 18.83 ) . Overall and cardiovascular mortality was similar in the two groups . CONCLUSIONS Among patients with a history of colorectal adenomas , the use of rofecoxib was associated with an increased cardiovascular risk Background —Nonsteroidal antiinflammatory drugs ( NSAIDs ) are reversible inhibitors of cyclooxygenase (COX)-1 and COX-2 . Whether transient and incomplete COX-1 inhibition with NSAIDs other than aspirin will translate into clinical cardioprotection is unclear . Some reports suggest that concurrent aspirin and ibuprofen might be associated with lower cardioprotection than aspirin alone because of a pharmacodynamic interaction . Methods and Results ——We conducted a cohort study with a nested case-control analysis . Overall , 4975 cases of acute myocardial infa rct ion ( MI ) and death from coronary heart disease ( CHD ) were identified ( January 1997 to December 2000 ) in the UK . A total of 20 000 controls were r and omly sample d , and frequency was matched to cases by age , sex , and calendar year . The incidence rate was 5.0 per 1000 person-years . The multivariate-adjusted OR for current NSAID use compared with nonuse was 1.07 ( 95 % CI , 0.95 to 1.20 ) . Treatment duration or daily dose did not change the results . The effect was similar among patients free of CHD history ( 1.04 ; 95 % CI , 0.90 to 1.20 ) and patients with previous history ( 1.12 ; 95 % CI , 0.91 to 1.38 ) . Estimates for individual NSAIDs were all comparable , with no major effect on the risk of acute MI . Naproxen was associated with an OR of 0.89 ( 95 % CI , 0.64 to 1.24 ) . The OR of aspirin and concurrent NSAIDs use was 1.10 ( 95 % CI , 0.89 to 1.37 ) compared with aspirin alone . We observed the same result when analyzing ibuprofen and aspirin taken concomitantly . Conclusions —This study could not demonstrate any detectable risk reduction of NSAIDs on the occurrence of MI . Our results do not support the existence of a clinical ly meaningful interaction between aspirin and NSAIDs , including ibuprofen Summary Objective : To evaluate the efficacy of 12 weeks of treatment with etoricoxib , a selective COX-2 inhibitor , in patients with osteoarthritis ( OA ) of the knee or hip . Methods : In the 12-week placebo- and active comparator-controlled period of a r and omized , double-blind study , eligible patients were treated with etoricoxib 60 mg once daily ( n = 224 ) , naproxen 500 mg twice daily ( n = 221 ) , or placebo ( n = 56 ) . Western Ontario McMaster 's Osteoarthritis Index ( WOMAC ) pain and physical function subscales and patient 's global assessment of disease status were primary end points . Key secondary and other end points were patient 's and investigator 's global assessment of response to therapy , WOMAC stiffness subscale , investigator 's global assessment of disease status , rescue paracetamol use , proportion of patients discontinuing due to lack of efficacy , and study joint tenderness . Results : Etoricoxib 60 mg demonstrated efficacy significantly superior to placebo ( p ≤ 0.005 ) and comparable to naproxen 500 mg twice daily as assessed by the primary efficacy end points . Secondary and other end points confirmed these results . Treatment effects were evident by day 2 , maximal by week 2 , and sustained over the entire 12 weeks . Etoricoxib was well tolerated for 12 weeks . Conclusions : Etoricoxib showed rapid and durable treatment effects in patients with OA of the knee or hip . Etoricoxib was generally well tolerated ABSTRACT Objective : To determine the efficacy and safety of lumiracoxib for knee osteoarthritis ( OA ) . Methods : This was a 13-week , multicentre , r and omized , double-blind , double-dummy , placebo-controlled study . Males or females aged ≥ 18 years with primary knee OA received lumiracoxib 100 mg od , lumiracoxib 100 mg od with a loading dose of 200 mg od for the first two weeks , celecoxib 200 mg od , or placebo . Main outcome measures : Co- primary variables , assessed at week 13 , were OA pain intensity in the target knee , patient 's global assessment of disease activity and the WOMAC total score . Other variables included OMERACT – OARSI responder rates and WOMAC subscale scores . Safety and tolerability were evaluated . Results : All active treatments were superior to placebo for all co- primary variables . No significant differences were observed between any active treatments . Mean reductions from baseline to week 13 for lumiracoxib 100 mg od , 100 mg od with loading dose , celecoxib and placebo , respectively , were : OA pain intensity in the target knee : 26.8 , 26.2 , 26.6 and 21.4 mm ( all p < 0.01 vs. placebo ) ; patient 's global assessment of disease activity : 25.1 , 21.9 , 22.9 and 18.9 mm ( all p < 0.05 vs. placebo ) ; WOMAC total score : 15.2 , 14.8 , 14.7 and 11.3 ( all p < 0.01 vs. placebo ) . Lumiracoxib was superior to placebo and similar to celecoxib for OMERACT – OARSI response and WOMAC subscale scores . Lumiracoxib was well tolerated . The incidence of adverse events was similar across groups . Conclusions : Lumiracoxib 100 mg od provided effective relief from the pain of knee OA , with efficacy similar to celecoxib 200 mg od , and was well tolerated CONTEXT Conventional nonsteroidal anti-inflammatory drugs ( NSAIDs ) are associated with a spectrum of toxic effects , notably gastrointestinal ( GI ) effects , because of inhibition of cyclooxygenase (COX)-1 . Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown . OBJECTIVE To determine whether celecoxib , a COX-2-specific inhibitor , is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs . DESIGN The Celecoxib Long-term Arthritis Safety Study ( CLASS ) , a double-blind , r and omized controlled trial conducted from September 1998 to March 2000 . SETTING Three hundred eighty-six clinical sites in the United States and Canada . PARTICIPANTS A total of 8059 patients ( > /=18 years old ) with osteoarthritis ( OA ) or rheumatoid arthritis ( RA ) were enrolled in the study , and 7968 received at least 1 dose of study drug . A total of 4573 patients ( 57 % ) received treatment for 6 months . INTERVENTIONS Patients were r and omly assigned to receive celecoxib , 400 mg twice per day ( 2 and 4 times the maximum RA and OA dosages , respectively ; n = 3987 ) ; ibuprofen , 800 mg 3 times per day ( n = 1985 ) ; or diclofenac , 75 mg twice per day ( n = 1996 ) . Aspirin use for cardiovascular prophylaxis ( < /=325 mg/d ) was permitted . MAIN OUTCOME MEASURES Incidence of prospect ively defined symptomatic upper GI ulcers and ulcer complications ( bleeding , perforation , and obstruction ) and other adverse effects during the 6-month treatment period . RESULTS For all patients , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76 % vs 1.45 % ( P = .09 ) and 2 . 08 % vs 3.54 % ( P = .02 ) , respectively . For patients not taking aspirin , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44 % vs 1.27 % ( P = .04 ) and 1.40 % vs 2.91 % ( P = .02 ) . For patients taking aspirin , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01 % vs 2.12 % ( P = .92 ) and 4.70 % vs 6.00 % ( P = .49 ) . Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss , GI intolerance , hepatotoxicity , or renal toxicity . No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs , irrespective of aspirin use . CONCLUSIONS In this study , celecoxib , at dosages greater than those indicated clinical ly , was associated with a lower incidence of symptomatic ulcers and ulcer complications combined , as well as other clinical ly important toxic effects , compared with NSAIDs at st and ard dosages . The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly . JAMA . 2000;284:1247 - BACKGROUND Non-steroidal anti-inflammatory drugs ( NSAIDs ) inhibit cyclo-oxygenase ( COX ) , which leads to suppression of COX-1-mediated production of gastrointestinal-protective prostagl and ins . Gastrointestinal injury is a common outcome . We compared the efficacy , safety , and tolerability of long-term therapy with celecoxib , a COX-1 sparing inhibitor of COX-2 , with diclofenac , a non-specific COX inhibitor . METHODS 655 patients with adult-onset rheumatoid arthritis of at least 6 months ' duration were r and omly assigned oral celecoxib 200 mg twice daily or diclofenac SR 75 mg twice daily for 24 weeks . Anti-inflammatory and analgesic activity and tolerability were assessed at baseline , every 4 weeks , and at week 24 . We assessed gastrointestinal safety by upper-gastrointestinal endoscopy within 7 days of the last treatment dose at centres where the procedure was available . Analysis was by intention-to-treat . FINDINGS 430 patients underwent endoscopy ( celecoxib n=212 , diclofenac n=218 ) . The two drugs were similar in management of rheumatoid arthritis pain and inflammation . Gastroduodenal ulcers were detected endoscopically in 33 ( 15 % ) patients treated with diclofenac and in eight ( 4 % ) in the celecoxib group ( p<0.001 ) . The rate of withdrawal for any gastrointestinal-related adverse event , most commonly abdominal pain , diarrhoea , and dyspepsia , was nearly three times higher in the diclofenac-treated group than in the celecoxib group ( 16 vs 6 % ; p<0.001 ) . INTERPRETATION Celecoxib showed sustained anti-inflammatory and analgesic activity similar to diclofenac , with a lower frequency of upper gastrointestinal ulceration or gastrointestinal adverse events , and tolerability was better OBJECTIVES To evaluate the clinical efficacy and tolerability of etoricoxib in the treatment of osteoarthritis ( OA ) of the knee and define the clinical ly active dose range for further clinical trials . METHODS This two-part , r and omized , double-blind , placebo- and active comparator-controlled trial was conducted in 617 adults with knee OA . In Part 1 ( 6 weeks ) , patients received placebo , etoricoxib 5 , 10 , 30 , 60 or 90 mg q.d . In Part 2 ( 8 weeks ) , patients received etoricoxib 30 , 60 or 90 mg q.d . or diclofenac 50 mg t.i.d . , predetermined at Part 1 allocation . Efficacy and safety were evaluated . Primary efficacy end-points were the Western Ontario and McMaster 's University Osteoarthritis Index ( WOMAC ) Pain subscale , Patient Global Assessment of Response to Therapy , and Investigator Global Assessment of Disease Status . RESULTS At 6 weeks , etoricoxib 5 , 10 , 30 , 60 and 90 mg each demonstrated clinical efficacy superior to placebo . Maximal efficacy was seen with 60 mg . In Part 2 , etoricoxib 30 , 60 and 90 mg were generally similar to diclofenac . Patients receiving etoricoxib 30 , 60 or 90 mg in Parts I and II had sustained effects over 14 weeks . All treatments were well tolerated . CONCLUSIONS Etoricoxib 60 mg once daily showed maximal efficacy in treating OA in this study . Etoricoxib 5 - 90 mg once daily was generally well tolerated in OA patients for up to 14 weeks OBJECTIVE To compare the efficacy and upper gastrointestinal ( GI ) safety of valdecoxib 20 and 40 mg daily with those of diclofenac 75 mg slow release ( SR ) twice daily in treating rheumatoid arthritis ( RA ) . METHODS Seven hundred and twenty-two patients with adult-onset RA were enrolled into this 26-week , r and omized , multicentre , double-blind , parallel-group study ( 246 in the valdecoxib 20 mg daily arm , 237 in the valdecoxib 40 mg daily arm and 239 in the diclofenac 75 mg SR daily arm ) . Acetylsalicylic acid use ( < or = 325 mg per day ) was similar across all groups : 5.4 % in the diclofenac group , 5.7 % in the valdecoxib 20 mg group and 5.9 % in the valdecoxib 40 mg group . Efficacy was measured by the Patient 's Assessment of Arthritis Pain [ visual analogue scale ( VAS ) ] and the modified Health Assessment Question naire ( mHAQ ) at baseline and at weeks 2 , 6 , 8 , 12 , 18 and 26 of treatment , or at early termination . Upper GI safety was evaluated by endoscopy at the end of treatment , which took place no more than 2 days after the last dose of study medication or at early termination . RESULTS Valdecoxib 20 and 40 mg daily were comparable to diclofenac 75 mg SR twice daily in treating the signs and symptoms of RA . No significant differences were observed between treatment groups with respect to mean changes from baseline in the Patient 's Assessment of Arthritis Pain ( VAS ) or mHAQ . The incidence of gastroduodenal ulcers in patients receiving valdecoxib 20 mg daily ( 6 % ) and valdecoxib 40 mg daily ( 4 % ) was significantly lower ( P < 0.001 ) than in patients receiving diclofenac 75 mg SR twice daily ( 16 % ) . Valdecoxib 20 mg daily was also associated with significantly improved GI tolerability ( P = 0.035 ) compared with diclofenac . CONCLUSIONS Single daily doses of valdecoxib 20 and 40 mg provided efficacy comparable to that of diclofenac , with a superior upper GI safety profile in the long-term treatment of RA patients In contrast to economic models that provide probabilistic estimates of economic impact , data extracted from clinical trials may be used to evaluate and compare actual re source utilization and costs . Health-care re source utilization and the costs of these re sources were compared from the perspective of the UK National Health Service using data obtained in a 6-month clinical trial of oral valdecoxib 20 mg once daily and diclofenac 75 mg twice daily for the symptomatic treatment of rheumatoid arthritis . However , calculated health-care costs were exclusive of drug acquisition costs because the price of valdecoxib was not available at the time of analysis . While the efficacy of the two treatments was similar , use of valdecoxib was associated with a reduction in total health-care costs amounting to approximately 200 British pounds per patient . This lower cost was associated with reduced use of health-care re sources for gastrointestinal serious adverse events ( gastrointestinal SAEs ) . In particular , the incidence of hospitalization and number of hospital days for gastrointestinal SAEs was lower in the valdecoxib group . Analysis of cost per gastrointestinal SAE favoured valdecoxib ( cost savings of 742 British pounds ) , suggesting that even when these events did occur they were less severe . When costs of gastrointestinal SAEs were averaged over the entire population , valdecoxib was suggested to have lower total costs per patient compared with diclofenac ( cost savings of 115 British pounds per patient ) , mainly result ing from significant savings in hospitalization costs ( 76.49 British pounds per patient ) . These data are consistent with economic models and suggest that the favourable gastrointestinal profile of valdecoxib observed in clinical trials will be of economic benefit BACKGROUND Cyclo-oxygenase-2 ( COX-2 ) selective inhibitors have been associated with an increased risk of thrombotic cardiovascular events in placebo-controlled trials , but no clinical trial has been reported with the primary aim of assessing relative cardiovascular risk of these drugs compared with traditional non-steroidal anti-inflammatory drugs ( NSAIDs ) . The MEDAL programme was design ed to provide a precise estimate of thrombotic cardiovascular events with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac . METHODS We design ed a prespecified pooled analysis of data from three trials in which patients with osteoarthritis or rheumatoid arthritis were r and omly assigned to etoricoxib ( 60 mg or 90 mg daily ) or diclofenac ( 150 mg daily ) . The primary hypothesis stated that etoricoxib is not inferior to diclofenac , defined as an upper boundary of less than 1.30 for the 95 % CI of the hazard ratio for thrombotic cardiovascular events in the per- protocol analysis . Intention-to-treat analyses were also done to assess consistency of results . These trials are registered at http://www . clinical trials.gov with the numbers NCT00092703 , NCT00092742 , and NCT00250445 . FINDINGS 34 701 patients ( 24 913 with osteoarthritis and 9 787 with rheumatoid arthritis ) were enrolled . Average treatment duration was 18 months ( SD 11.8 ) . 320 patients in the etoricoxib group and 323 in the diclofenac group had thrombotic cardiovascular events , yielding event rates of 1.24 and 1.30 per 100 patient-years and a hazard ratio of 0.95 ( 95 % CI 0.81 - 1.11 ) for etoricoxib compared with diclofenac . Rates of upper gastrointestinal clinical events ( perforation , bleeding , obstruction , ulcer ) were lower with etoricoxib than with diclofenac ( 0.67 vs 0.97 per 100 patient-years ; hazard ratio 0.69 [ 0.57 - 0.83 ] ) , but the rates of complicated upper gastrointestinal events were similar for etoricoxib ( 0.30 ) and diclofenac ( 0.32 ) . INTERPRETATION Rates of thrombotic cardiovascular events in patients with arthritis on etoricoxib are similar to those in patients on diclofenac with long-term use of these drugs STUDY OBJECTIVE To evaluate the risk of acute myocardial infa rct ion during current exposure to nonsteroidal antiinflammatory drugs ( NSAIDs ) . DESIGN Retrospective case-control analysis . SETTING General practice offices . SUBJECTS A total of 8688 case patients , aged 89 years or younger , with a first-time acute myocardial infa rct ion and 33,923 control subjects matched on age , sex , calendar time , and general practice attended . INTERVENTION The United Kingdom General Practice Research Data base was search ed for potential cases of first-time acute myocardial infa rct ion between January 1995 and April 2001 . Control subjects without acute myocardial infa rct ion were identified at r and om . MEASUREMENTS AND MAIN RESULTS Exposure to NSAIDs was assessed , and 650 case patients and 2339 control subjects were found to be currently taking NSAIDs . After adjusting for various risk factors for acute myocardial infa rct ion ( e.g. , hypertension , hyperlipidemia , diabetes mellitus , ischemic heart disease , body mass index , smoking ) , the relative risk ( expressed as odds ratio [ OR ] ) of acute myocardial infa rct ion was 1.07 ( 95 % confidence interval [ CI ] 0.96 - 1.19 ) for subjects with current NSAID exposure compared with those not taking NSAIDs . The adjusted OR for current diclofenac use was 1.23 ( 95 % CI 1.00 - 1.51 ) , for current ibuprofen use 1.16 ( 95 % CI 0.92 - 1.46 ) , and for current naproxen use 0.96 ( 95 % CI 0.66 - 1.38 ) compared with those not taking NSAIDs . Current aspirin use combined with current NSAID use was associated with a statistically significant risk reduction ( adjusted OR 0.74 , 95 % CI 0.57 - 0.97 ) , compared with nonuse of NSAIDs and aspirin . Current use of aspirin together with current use of ibuprofen yielded an adjusted OR of 0.69 ( 95 % CI 0.42 - 1.15 ) . CONCLUSIONS Our results provide additional evidence that the risk of first-time acute myocardial infa rct ion during current use of NSAIDs is not material ly altered . We found no evidence for a reduced cardioprotective effect of aspirin with concomitant NSAID use Context Most trials that compare gastrointestinal effects of rofecoxib and nonsteroidal anti-inflammatory drugs examine highly selected patient sample s. Contribution This r and omized , double-blind , placebo-controlled trial of 5557 patients with osteoarthritis includes patients typical of community practice : older patients with comorbid conditions and patients using aspirin for cardiovascular prophylaxis . Rofecoxib and naproxen therapies were discontinued by 5.9 % and 8.1 % of patients , respectively , because of gastrointestinal side effects . Among low-dose aspirin users , 5.2 % taking rofecoxib and 9.4 % taking naproxen discontinued using the drugs . Caution s The trial tested daily doses of medicines for a short period ( 3 months ) rather than long-term , intermittent dosing based on symptoms . The Editors Osteoarthritis usually affects older persons who frequently take many medications for comorbid conditions ( 1 - 3 ) . Patients with osteoarthritis often use nonsteroidal anti-inflammatory drugs ( NSAIDs ) to treat symptoms because of the analgesic and anti-inflammatory effects of these drugs ; in addition , NSAIDs are preferred to simple analgesics such as acetaminophen or mild opiates ( 4 ) . Gastrointestinal ( GI ) toxicity is a common side effect of dual cyclooxygenase (COX)-1- and COX-2-inhibiting NSAIDs . In older patients , GI toxicity is increased by concomitant aspirin use , previous GI intolerability , and other comorbid conditions . The 2 main forms of NSAID-induced GI toxicity manifest as serious alterations in mucosal integrity ( leading to perforations , ulcers , and GI bleeding ) and GI intolerability , which is more common . Gastrointestinal intolerability is exemplified by dyspepsia , constipation , and abdominal pain that in its most severe form prompts discontinuation of therapy or initiation of treatment with GI protective agents . Nonsteroidal anti-inflammatory drugs affect prostagl and in synthesis through dual inhibition of COX isoforms COX-1 and COX-2 ( 5 - 8 ) . Cyclooxygenase-1 is responsible for producing prostanoids involved in GI mucosal protection and normal platelet function , while COX-2 leads to the production of prostagl and ins that mediate pain and inflammation ( 9 - 11 ) . Gastrointestinal toxicity induced by NSAIDs is thought to be principally caused by inhibition of COX-1 ( 12 , 13 ) . Rofecoxib is a COX-2 selective inhibitor and spares COX-1 inhibition . A pooled analysis of 8 efficacy trials in osteoarthritis and a large prospect i ve study of outcomes in rheumatoid arthritis showed that rofecoxib maintained efficacy and result ed in a significantly lower incidence of serious GI toxicity compared with nonspecific dual COX inhibitors ( 14 , 15 ) . We prospect ively compared rofecoxib and a dual COX-inhibiting NSAID ( naproxen ) in relatively unselected patients with characteristics typical of persons seen in clinical practice . Our study sample included elderly patients with comorbid conditions . Forty-nine percent had hypertension , 60 % had a history of cardiovascular events , and 47 % had a history of GI events , including previous discontinuation of therapy with arthritis medication because of GI symptoms ( 15 % ) . Methods Study Sample Physicians predominantly at primary care practice s associated with investigational sites recruited patients from their existing practice s or recruited new patients presenting with osteoarthritis who were screened for study participation . Patients were at least 40 years of age and had osteoarthritis of the knee , hip , h and , or spine that had been symptomatic for more than 6 months and required regular treatment with an NSAID or acetaminophen . Osteoarthritis was classified as American College of Rheumatology functional class I , II , or III . Patients were excluded if , in the opinion of the investigator , they had a potentially confounding concurrent disease . Patients were not excluded because of a history of dyspepsia , ulcer , GI bleeding , or other GI symptoms besides history of malabsorption as long as they did not have a history of sustained use ( > 4 consecutive days ) of GI protective medications such as H2-blockers , antacids , and proton-pump inhibitors during the month before study entry . Low-dose aspirin ( 100 mg/d ) was allowed if it had been taken for cardiovascular prophylaxis before r and omization . Study Design We enrolled 5557 patients at 600 study sites , 581 in the United States and 19 in Sweden . At the baseline visit , written informed consent and medical history were obtained and eligible patients underwent physical examination . Baseline laboratory tests included complete blood count , serum chemistry studies , and urinalysis . In addition , at baseline , patients completed a Patient Global Assessment of Disease Status ( PGADS ) question naire , which is a 0- to 100-mm visual analogue scale , and the Medical Outcomes Study 36-item Short Form Health Survey , which measured quality of life . Patients who primarily had osteoarthritis of the h and completed the Australian/Canadian ( AUSCAN ) Osteoarthritis H and Index ( 16 ) . Following an initial overview of the question naires with study staff , patients completed all efficacy questions without assistance from site personnel . A computer-generated r and omization schedule was used to assign eligible patients in a 1:1 ratio to receive rofecoxib , 25 mg/d , or naproxen , 500 mg twice daily . Allocation was balanced by study site . To maintain blinding , patients took rofecoxib plus a naproxen placebo or naproxen plus a rofecoxib placebo in the morning and naproxen or naproxen placebo in the evening . Acetaminophen ( 2600 mg/d ) was available to all patients as needed during the study as rescue medication for intolerable pain . Patients were also permitted to use concomitant GI protective medications during the trial ( including proton-pump inhibitors , antacids , and H2-blockers ) if needed to treat GI symptoms . Investigational site staff contacted patients by telephone for collection of safety data at weeks 3 and 9 of therapy . At week 6 and week 12 ( or discontinuation ) , patients returned to the office and were question ed by a clinical investigator about adverse events and changes in medical therapy since the last visit . A physical examination was performed , vital signs were recorded , and patients completed the PGADS question naire . The investigator identified adverse events on the basis of physical examination of the patient and patient-reported adverse events ; he or she also evaluated adverse events for severity and determined causality . Study medication , adherence , and rescue acetaminophen use were recorded . At week 12 ( or discontinuation ) , a physical examination was performed ; patients completed the Medical Outcomes Study 36-item Short Form Health Survey ; and complete blood count , serum chemistry studies , and urinalysis were done . Patients with h and osteoarthritis completed the AUSCAN Osteoarthritis H and Index . Adherence was assessed by measuring pill count ( doses taken compared with doses scheduled ) during study site visits at weeks 6 and 12 . The investigators were instructed to report all laboratory and clinical adverse events that occurred during treatment and within 14 days of discontinuation of therapy with the study drug . Patients were instructed to contact an investigator if they wanted to discontinue treatment . An investigator could recommend that a patient discontinue treatment because of clinical or laboratory assessment s. Ethical Considerations The study was conducted with consideration for the protection of patients , as outlined in the Declaration of Helsinki , and was approved by the appropriate institutional review boards or ethical review committees . All patients gave written informed consent before undergoing any examination or study procedure . Statistical Analysis All analyses were prespecified in the protocol and detailed in the data analysis plan . The primary end point , GI tolerability , was defined as discontinuation due to GI adverse events or abdominal pain during the 12-week treatment period . The primary time point or exposure period was defined as end of study , that is , from the time of the first dose up to 14 days after the 12-week visit ( day 98 ) or discontinuation . For time-to-event data , the log-rank test was used to compare the cumulative incidence curves for discontinuation due to GI adverse events . The Cox proportional-hazards model with treatment as a factor was used to estimate relative risk ( RR ) and corresponding 95 % CIs for rofecoxib compared with naproxen . Similar analyses were conducted for any concomitant use of GI medications during the trial . Incidence of clinical and laboratory adverse events was tabulated by treatment group . Additional tabulations were prepared for serious adverse events , drug-related adverse events , and adverse events that result ed in study withdrawal . To determine the incidence of perforations , ulcers , bleeding , and cardiovascular events , two expert external committees ( GI and cardiovascular ) evaluated blinded data obtained from patients suspected of having an event that required adjudication , according to previously described criteria ( 17 ) . A Cox proportional-hazards model with treatment effect as a factor was used to estimate RRs and corresponding CIs for perforations , ulcers , bleeding , or cardiovascular events in the rofecoxib group compared with the naproxen group . The Fisher exact test was used to compare incidence of confirmed perforations , ulcers , bleeding , thrombotic events , and cardiovascular events according to Antiplatelet Trialists ' Collaboration criteria ( 17 ) . Summaries were prepared for all other safety variables . The PGADS question naire was measured on a 0- to 100-mm visual analogue scale and was evaluated at baseline , week 6 , and week 12 . The analysis of PGADS applied a last-observation-carried-forward approach in which missing data at week 12 were imputed by data from week 6 . Missing baseline and week 6 data were not imputed . For each efficacy evaluation , differences in treatment means and corresponding CIs were estimated CONTEXT In vitro studies have shown that celecoxib inhibits cyclooxygenase 2 ( COX-2 ) but not COX-1 , suggesting that this drug may have anti-inflammatory and analgesic activity without adverse upper gastrointestinal ( GI ) tract effects that result from COX-1 inhibition . OBJECTIVE To test whether celecoxib has efficacy as an anti-inflammatory and analgesic with reduced GI tract mucosal damage compared with conventional nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis . DESIGN R and omized , multicenter , placebo-controlled , double-blind trial lasting 12 weeks , with follow-up at weeks 2 , 6 , and 12 , from September 1996 thorugh February 1998 . SETTING Seventy-nine clinical sites in the United States and Canada . PATIENTS A total of 1149 patients aged 18 years or older with symptomatic rheumatoid arthritis who met inclusion criteria were r and omized ; 688 ( 60 % ) of these completed the study . INTERVENTIONS Patients were r and omized to receive celecoxib , 100 mg , 200 mg , or 400 mg twice per day ( n = 240 , 235 , and 218 , respectively ) ; naproxen , 500 mg twice per day ( n = 225 ) ; or placebo ( n = 231 ) . MAIN OUTCOME MEASURES Improvement in signs and symptoms of rheumatoid arthritis as assessed using st and ard measures of efficacy and GI tract safety as assessed by upper GI tract endoscopy before and after treatment , compared among treatment groups . RESULTS All dosages of celecoxib and naproxen significantly improved the signs and symptoms of arthritis compared with placebo . Maximal anti-inflammatory and analgesic activity was evident within 2 weeks of initiating treatment and was sustained throughout the 12 weeks . The incidence of endoscopically determined gastroduodenal ulcers in placebo-treated patients was 4 ( 4 % ) of 99 , and the incidences across all dosages of celecoxib were not significantly different ( P>.40 ) : 9 ( 6 % ) of 148 with 100 mg twice per day , 6 ( 4 % ) of 145 with 200 mg twice per day , and 8 ( 6 % ) of 130 with 400 mg twice per day . In contrast , the incidence with naproxen was 36 ( 26 % ) of 137 , significantly greater than either placebo or celecoxib ( P<.001 ) . The overall incidences of GI tract adverse effects were 19 % for placebo ; 28 % , 25 % , and 26 % for celecoxib 100 mg , 200 mg , and 400 mg twice per day , respectively ; and 31 % for naproxen . CONCLUSION In this study , all dosages of celecoxib were efficacious in the treatment of rheumatoid arthritis and did not affect COX-1 activity in the GI tract mucosa as evidence d by less frequent incidence of endoscopic ulcers compared with naproxen Objective : To evaluate the efficacy and tolerability of rofecoxib 25 mg and 50 mg once daily versus placebo and naproxen 500 mg twice daily in patients with RA . Methods : Eligible patients were r and omized ( double-blind ) to placebo ( n = 289 ) , rofecoxib 25 mg ( n = 306 ) , 50 mg ( n = 286 ) once daily , or naproxen ( n = 142 ) for 12 weeks . Efficacy assessment s included the ACR core set , with prespecified primary endpoints : patient and investigator global assessment s of disease activity , tender and swollen joint counts . Investigator-reported adverse experiences , routine laboratory and vital sign measurements were monitored . Results : Rofecoxib 25 mg , 50 mg , and naproxen provided similar treatment effects , significantly different from placebo , consistent with improvement , for all primary endpoints . Effects were evident at the earliest assessment ( week 2 ) and sustained for 12 weeks . All treatments were generally well-tolerated . Conclusions : Rofecoxib 25 mg once daily had similar efficacy to naproxen 500 mg twice daily ( a st and ard dose ) . No additional benefit was seen with 50 mg rofecoxib BACKGROUND Recent debate has emerged regarding the cardiovascular safety of selective cyclooxygenase 2 inhibitors and the possible cardioprotective effect of naproxen sodium . We compared the rates of acute myocardial infa rct ion ( AMI ) among elderly patients dispensed selective cyclooxygenase 2 inhibitors , naproxen , and nonselective nonnaproxen nonsteroidal anti-inflammatory drugs ( NSAIDs ) . METHODS We conducted a population -based retrospective cohort study using administrative health care data from Ontario , Canada , from April 1 , 1998 , to March 31 , 2001 . We identified NSAID-naive cohorts of subjects aged 66 years and older in whom treatment was initiated with celecoxib ( n = 15 271 ) , rofecoxib ( n = 12 156 ) , naproxen ( n = 5669 ) , and nonnaproxen nonselective NSAIDs ( n = 33 868 ) , along with a r and omly selected control cohort not exposed to NSAIDs ( n = 100 000 ) . Multivariate Cox proportional hazards models were used to compare AMI rates between study drug groups while controlling for potential confounders . RESULTS Relative to control subjects , the multivariate model showed no significant differences in AMI risk for new users of celecoxib ( adjusted rate ratio [ aRR ] , 0.9 ; 95 % confidence interval [ CI ] , 0.7 - 1.2 ) , rofecoxib ( aRR , 1.0 ; 95 % CI , 0.8 - 1.4 ) , naproxen ( aRR , 1.0 ; 95 % CI , 0.6 - 1.7 ) , or nonnaproxen nonselective NSAIDs ( aRR , 1.2 ; 95 % CI , 0.9 - 1.4 ) . CONCLUSIONS The findings of this observational study suggest no increase in the short-term risk of AMI among users of selective cyclooxygenase 2 inhibitors as commonly used in clinical practice . Furthermore , the findings do not support a short-term reduced risk of AMI with naproxen OBJECTIVES To evaluate the use of starting doses of rofecoxib and nabumetone in patients with osteoarthritis ( OA ) of the knee . DESIGN A 6-week , r and omized , parallel-group , double-blind , placebo-controlled study . SETTING One hundred thirteen outpatient sites in the United States . PARTICIPANTS A total of 1,042 male and female patients aged 40 and older with OA of the knee ( > 6 months ) . INTERVENTIONS Rofecoxib 12.5 mg once a day ( n=424 ) , nabumetone 1,000 mg once a day ( n=410 ) , or placebo ( n=208 ) for 6 weeks . MEASUREMENTS The primary efficacy endpoint was patient global assessment of response to therapy ( PGART ) over 6 weeks , which was also specifically evaluated over the first 6 days . The main safety measure was adverse events during the 6 weeks of treatment . RESULTS The percentage of patients with a good or excellent response to therapy as assessed using PGART at Week 6 was significantly higher with rofecoxib ( 55.4 % ) than nabumetone ( 47.5 % ; P=.018 ) or placebo ( 26.7 % ; P<.001 vs rofecoxib or nabumetone ) . Median time to first report of a good or excellent PGART response was significantly shorter in patients treated with rofecoxib ( 2 days ) than with nabumetone ( 4 days , P=.002 ) and placebo ( > 5 days , P<.001 ) ( nabumetone vs placebo ; P=.007 ) . The safety profiles of rofecoxib and nabumetone were generally similar , including gastrointestinal , hypertensive , and renal adverse events . CONCLUSION Rofecoxib 12.5 mg daily demonstrated better efficacy over 6 weeks of treatment and quicker onset of OA efficacy over the first 6 days than nabumetone 1,000 mg daily . Both therapies were generally well tolerated OBJECTIVE To compare the efficacy of the COX-2 specific inhibitor valdecoxib with the conventional NSAID naproxen and placebo in treating rheumatoid arthritis ( RA ) . METHODS This multi-centre , r and omized , double-blind , placebo-controlled trial compared the efficacy and safety of valdecoxib 10 mg ( n=209 ) , 20 mg ( n=212 ) or 40 mg once daily ( q.d . ) ( n=221 ) with naproxen 500 mg b.i.d . ( n=226 ) or placebo ( n=222 ) , in treating the signs and symptoms of RA . Efficacy was assessed by the number of patients responding to treatment according to the American College of Rheumatology-Responder Index ( ACR-20 ) . RESULTS ACR-20 response was recorded for all r and omized patients who received a single dose of study medication ( above ) . Valdecoxib , at all administered doses , produced significant improvements in the ACR-20 Responder Index at weeks 2 , 6 and 12 compared with placebo ( P < or=0.01 ) . Valdecoxib and naproxen did not differ in terms of ACR-20 response rate and the three doses of valdecoxib were similar to one another . All three doses of valdecoxib were well tolerated . CONCLUSIONS Single daily doses of valdecoxib 10 , 20 and 40 mg demonstrated efficacy that was superior to placebo and similar to naproxen in treating the signs and symptoms of RA . All three doses provided similar levels of efficacy OBJECTIVE To compare the effect of celecoxib vs placebo treatment on clinical and gait variables in knee osteoarthritis ( OA ) patients ; focusing on the efficiency of the locomotor mechanism . METHODS STUDY DESIGN A prospect i ve , r and omised , double-blind placebo-controlled trial . PATIENTS Eight adult patients with painful OA of the knee . OUTCOME MEASURES Clinical assessment included knee pain assessed by the visual analogue scale , range of knee motion assessed by goniometer , and locomotor function status assessed by a Knee Score Scale . Gait was assessed by means of instrumented analysis including synchronous kinematic , dynamic , electromyographic , and energetic recordings . STATISTICAL ANALYSIS The effect of treatment on the primary variable , the efficiency of the locomotor mechanism , and on secondary clinical and gait variables was assessed by the Hills and Armitage non-parametric approach . RESULTS Celecoxib treatment improved the efficiency of the locomotor mechanism significantly . Among the secondary outcome measures assessed , celecoxib treatment improved walking cadence and reduced the knee pain significantly . CONCLUSION This study shows that celecoxib is effective in improving locomotor function and pain in patients with knee OA OBJECTIVE To directly compare the efficacy and safety of etoricoxib , 30 mg once daily , ibuprofen , 800 mg 3 times daily , and placebo for treatment of osteoarthritis ( OA ) of the hip and knee . PATIENTS AND METHODS A r and omized , double-blind , placebo-controlled trial of patients with OA of the knee or hip was performed between February 2003 and November 2003 in 61 medical centers in the United States . Qualified patients aged 40 to 89 years were r and omized to receive placebo , etoricoxib , 30 mg once daily , or ibuprofen , 800 mg 3 times daily , for 12 weeks . Primary efficacy end points Included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscales and Patient Global Assessment of Disease Status . Response to treatment was assessed by the time-weighted average change from baseline over 12 weeks . RESULTS In 528 patients , baseline values for the 3 primary end points ranged from 67.78 to 72.60 mm ( 0 - 100 mm visual analog scale ) . Near-maximal efficacy was achieved by week 2 with both active treatments and sustained over the course of the trial . During the 12-week period , least squares mean changes in the primary end points ( Western Ontario and McMaster Universities Osteoarthritis Index and Patient Global Assessment of Disease Status subscales ) ranged from -16.53 to -13.55 mm , -27.89 to -23.68 mm , and -26.53 to -22.97 mm in the placebo , etoricoxib , and Ibuprofen groups , respectively . Both etoricoxib and ibuprofen were more effective ( P<.001 ) than placebo for all primary end points . Etoricoxib and ibuprofen treatment responses for the primary end points were determined to be comparable with use of prespecified comparability criteria . Results for all other efficacy end points were consistent with responses observed for the primary end points . Etoricoxib and ibuprofen generally were well tolerated . CONCLUSION For patients with OA , treatment with etoricoxib , 30 mg/d , is well tolerated and provides sustained clinical effectiveness that is superior to placebo and comparable to ibuprofen , 2400 mg/d OBJECTIVE : Nonsteroidal anti-inflammatory drugs ( NSAIDs ) block prostagl and in production by inhibiting cyclooxygenase ( COX ) ; they are believed to cause gastroduodenal damage by inhibiting the COX-1 isoform and to have analgesic and anti-inflammatory effects by inhibiting the COX-2 isoform . As compared to conventional NSAIDs , celecoxib , a COX-2 specific inhibitor , has been shown in previous single posttreatment endoscopy studies to be associated with lower gastroduodenal ulcer rates . In response to concerns that such studies may under-represent ulceration rates , the present serial endoscopy study was design ed to compare cumulative gastroduodenal ulcer rates associated with the use of celecoxib to those of naproxen , a conventional NSAID . METHODS : In this double-blind , parallel-group , multicenter study , 537 patients with osteoarthritis ( OA ) or rheumatoid arthritis ( RA ) were r and omized to treatment with celecoxib 200 mg b.i.d . ( n = 270 ) or naproxen 500 mg b.i.d . ( n = 267 ) for 12 wk . Gastroduodenal damage was determined from esophagogastroduodenoscopy after 4 , 8 , and 12 wk of therapy . Arthritis efficacy was evaluated with Patient 's and Physician 's Global Assessment s. RESULTS : Gastroduodenal ulcer rates after celecoxib and naproxen treatment were 4 % versus 19 % in the 0–4 wk interval ( p < 0.001 ) , 2 % versus 14 % in the 4–8 wk interval ( p < 0.001 ) , and 2 % versus 10 % in the 8–12 wk interval ( p < 0.001 ) , respectively . After 12 wk of treatment , the cumulative incidence of gastroduodenal ulcers was 9 % with celecoxib and 41 % with naproxen . In the celecoxib group , gastroduodenal ulcers were significantly associated with Helicobacter pylori status ( p < 0.05 ) , concurrent aspirin usage ( p = 0.001 ) , and a history of ulcer ( p = 0.010 ) , but not with disease type ( OA/RA ) , age , gender , other relevant medical histories , or concurrent corticosteroid or disease-modifying antirheumatic drugs usage ( p > 0.05 ) . Celecoxib produced a significantly lower incidence rate of both gastric ( p < 0.001 ) and duodenal ( p < 0.030 ) ulcers . The two agents produced similar improvements in Patient 's and Physician 's Global Assessment s of arthritis efficacy . The incidence of adverse events and withdrawal rates did not differ significantly between treatments . CONCLUSIONS : As compared to naproxen ( 500 mg b.i.d . ) , use of celecoxib ( 200 mg b.i.d . ) , a COX-2 specific agent , at the recommended RA dose and twice the most frequently prescribed OA dose , was associated with lower rates of gastric , duodenal , and gastroduodenal ulcers but had comparable efficacy , in patients with OA and RA BACKGROUND The potential for cyclo-oxygenase 2 (COX2)-selective inhibitors to increase the risk for myocardial infa rct ion is controversial . The Therapeutic Arthritis Research and Gastrointestinal Event Trial ( TARGET ) aim ed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs , naproxen and ibuprofen . METHODS 18325 patients age 50 years or older with osteoarthritis were r and omised to lumiracoxib 400 mg once daily ( n=9156 ) , naproxen 500 mg twice daily ( 4754 ) , or ibuprofen 800 mg three times daily ( 4415 ) in two sub studies of identical design . R and omisation was stratified for low-dose aspirin use and age . The primary cardiovascular endpoint was the Antiplatelet Trialists ' Collaboration endpoint of non-fatal and silent myocardial infa rct ion , stroke , or cardiovascular death . Analysis was by intention to treat . FINDINGS 81 ( 0.44 % ) patients did not start treatment and 7120 ( 39 % ) did not complete the study . At 1-year follow-up , incidence of the primary endpoint was low , both with lumiracoxib ( 59 events [ 0.65 % ] ) and the non-steroidal anti-inflammatory drugs ( 50 events [ 0.55 % ] ; hazard ratio 1.14 [ 95 % CI 0.78 - 1.66 ] , p=0.5074 ) . Incidence of myocardial infa rct ion ( clinical and silent ) in the overall population in the individual sub studies was 0.38 % with lumiracoxib ( 18 events ) versus 0.21 % with naproxen ( ten ) and 0.11 % with lumiracoxib ( five ) versus 0.16 % with ibuprofen ( seven ) . In the naproxen sub study , rates of myocardial infa rct ion ( clinical and silent ) did not differ significantly compared with lumiracoxib in the population not taking low-dose aspirin ( hazard ratio 2.37 [ 95 % CI 0.74 - 7.55 ] , p=0.1454 ) , overall ( 1.77 [ 0.82 - 3.84 ] , p=0.1471 ) , and in patients taking aspirin ( 1.36 [ 0.47 - 3.93 ] , p=0.5658 ) . In the ibuprofen sub study , these rates did not differ between lumiracoxib and ibuprofen in the population not taking low-dose aspirin ( 0.75 [ 0.20 - 2.79 ] , p=0.6669 ) , overall ( 0.66 [ 0.21 - 2.09 ] , p=0.4833 ) , and in patients taking aspirin ( 0.47 [ 0.04 - 5.14 ] , p=0.5328 ) . INTERPRETATION The primary endpoint , including incidence of myocardial infa rct ion , did not differ between lumiracoxib and either ibuprofen or naproxen , irrespective of aspirin use . This finding suggests that lumiracoxib is an appropriate treatment for patients with osteoarthritis , who are often at high cardiovascular risk and taking low-dose aspirin OBJECTIVE To assess the efficacy , safety , and tolerability of etoricoxib , a cyclooxygenase 2 ( COX-2 ) selective inhibitor , administered continuously over 52 weeks for the treatment of ankylosing spondylitis ( AS ) . METHODS This 2-part , multicenter , double-blind , parallel-group , 52-week study evaluated 2 doses of etoricoxib ( 90 and 120 mg ) compared with naproxen at 1,000 mg . A 6-week , active-comparator- and placebo-controlled period ( part I ) was followed by a 46-week active-comparator-controlled period ( part II ) . The primary outcome measures ( on 100-mm visual analog scales ) were patient 's assessment of spine pain , patient 's global assessment of disease activity , and the Bath Ankylosing Spondylitis Functional Index . RESULTS Of the 387 patients r and omized to receive treatment , 301 ( 77.8 % ) completed part I and 284 ( 75.9 % ) completed part II . Compared with placebo over 6 weeks , those receiving 90 mg etoricoxib , 120 mg etoricoxib , and naproxen demonstrated significantly ( P < 0.001 ) greater improvement in all primary end points ; treatment effects ( expressed as the difference in least squares mean change versus placebo ) were 21 - 29 mm for spine pain , 18 - 25 mm for disease activity , and 11 - 15 mm for function . Compared with patients receiving naproxen , significantly greater improvement in all primary end points was demonstrated in the combined group receiving either 90 mg etoricoxib or 120 mg etoricoxib over 6 weeks , in each individual etoricoxib treatment group over 6 weeks , and in the combined etoricoxib group over 1 year ( all P < 0.05 ) ; results for secondary and exploratory end points were generally consistent with those from the primary analysis . Among all groups , there were no significant differences in the incidence of overall clinical , drug-related , or serious adverse experiences ( AEs ) and discontinuations due to AEs . Safety observations during part II were generally consistent with those in part I. CONCLUSION Etoricoxib at doses of 90 mg and 120 mg demonstrated superior efficacy compared with placebo over 6 weeks , and compared with naproxen over 1 year . These study results demonstrate that etoricoxib is generally safe , well-tolerated , and efficacious for the treatment of AS BACKGROUND Non-steroidal anti-inflammatory drugs ( NSAIDs ) are widely used to treat osteoarthritis ( OA ) , though their long-term efficacy is uncertain . We report a comparison of the symptomatic responses to therapy with tiaprofenic acid , indomethacin and placebo over 5 yr . METHODS A parallel-group , r and omized , single-blind trial of patients with knee OA recruited 812 patients from 20 centres ; 307 patients received tiaprofenic acid ( 300 mg b.d . ) , 202 indomethacin ( 25 mg t.d.s . ) and 303 matching placebo for up to 5 yr . At the end of the parallel-group study , patients receiving tiaprofenic acid or placebo entered a 4-week blinded cross-over study of tiaprofenic acid or placebo , both given for 2 weeks . Assessment s were at baseline , 4 weeks , then at 6-month intervals for up to 5 yr in the parallel group study and at 2-week intervals in the cross-over study . They comprised pain scores , duration of morning stiffness , patients ' global assessment s , paracetamol consumption , adverse reactions , withdrawals and functional outcomes . RESULTS There were significant falls in overall pain scores in patients receiving NSAIDs compared with placebo at 4 weeks in the parallel-group phase . Thereafter there were no advantages favouring active therapy . In the cross-over phase , pain scores were significantly lower in patients receiving tiaprofenic acid than placebo . Patients who had been receiving long-term tiaprofenic acid showed significant rises in their pain scores when receiving placebo therapy and vice versa . Adverse events were reported by 61 % of patients receiving tiaprofenic acid , 63 % on indomethacin and 51 % on placebo . Potentially severe side-effects were rare ; for example , there were only three cases of gastrointestinal bleeding on NSAIDs . The pattern of withdrawal was similar in patients taking NSAIDs and placebo in the parallel-group study ; at 48 weeks 53 % of the patients remained on tiaprofenic acid , 50 % on indomethacin and 54 % on placebo . CONCLUSIONS NSAIDs significantly reduce overall pain over 4 weeks . This short-term responsiveness is retained , and even after several years of therapy with tiaprofenic acid pain scores increased over 2 weeks when it was changed to placebo . Our results do not show long-term benefits from the use of NSAIDs in OA and the majority of patients had persisting pain and disability despite therapy OBJECTIVES : Dyspepsia and related gastrointestinal ( GI ) symptoms are commonly reported by patients taking nonspecific nonsteroidal anti-inflammatory drugs ( NSAIDs ) and significantly impact treatment effectiveness , cost , and quality of life . This study sought to evaluate dyspepsia-related health in osteoarthritis ( OA ) and rheumatoid arthritis ( RA ) patients taking valdecoxib compared with patients taking nonspecific NSAIDs . METHODS : Analysis of two separate , double-blind , placebo-controlled studies : one in RA patients r and omized to placebo , valdecoxib ( 10 and 20 mg once daily [ o.d . ] ) and naproxen ( 500 mg twice daily [ b.i.d . ] ) ; one in OA patients r and omized to placebo , valdecoxib ( 10 and 20 mg o.d . ) , diclofenac ( 75 mg b.i.d . ) , or ibuprofen ( 800 mg three times daily [ t.i.d . ] ) . Study population comprised patients with RA in flare or clinical ly documented OA who required chronic symptomatic treatment with NSAIDs/analgesics . Dyspepsia-related health was evaluated at baseline and weeks 2 , 6 , and 12 ( or early termination ) using the vali date d Severity of Dyspepsia Assessment ( SODA ) question naire . This patient self-report tool consists of scales for evaluating dyspepsia pain intensity , nonpain symptoms , and satisfaction . Analysis was based on the intent-to-treat population with the last observation carried forward . RESULTS : Valdecoxib was significantly better at endpoint than st and ard doses of naproxen , diclofenac , and ibuprofen for pain intensity scores ( p < 0.05 ) , and provided significantly improved nonpain symptom and satisfaction scores compared with naproxen for patients with RA ( p < 0.05 ) . For RA patients , the difference between valdecoxib and naproxen pain intensity scores were clinical ly meaningful ; at all the time points , significantly fewer patients receiving valdecoxib reported severe dyspepsia pain intensity increases ( ≥10 points ) than those receiving naproxen . At 12 wk , fewer patients receiving valdecoxib reported severe dyspepsia pain intensity increases versus those receiving ibuprofen and diclofenac . CONCLUSIONS : The GI tolerability of valdecoxib is superior to that of nonspecific NSAIDs , and therefore can potentially have a favorable impact on patient quality of life Nonsteroidal anti-inflammatory drugs . ( NSAIDs ) inhibit both cyclooxygenase (COX)-1 and COX-2 isoenzymes and are effective in the treatment of inflammatory disorders . This 8-week , double-masked , placebo-controlled trial was undertaken to assess the safety profile , tolerability , and effective dose range of once-daily rofecoxib , a COX-2-specific inhibitor , in the treatment of rheumatoid arthritis ( RA ) . After a 3- to 15-day washout of prior NSAID therapy , 658 patients were r and omly allocated to receive placebo or rofecoxib 5 mg , 25 mg , or 50 mg once daily . Safety profile , tolerability , and efficacy were evaluated after 2 , 4 , and 8 weeks of therapy . Six hundred fifty-eight patients ( 168 , 158 , 171 , and 161 in the placebo and 5-mg , 25-mg , and 50-mg rofecoxib groups , respectively ) were enrolled at 79 clinical centers in the United States . Mean age was 55 years , mean duration of RA was 10 years , and 506 ( 77 % ) of the 658 patients were female . All groups had similar baseline demographic characteristics . Patients taking rofecoxib 25 and 50 mg showed significant clinical improvement compared with those taking placebo ; 43.9 % in the rofecoxib 25-mg group and 49.7 % in the rofecoxib 50-mg group completed the treatment period and achieved an American College of Rheumatology 20 response ( P = 0.025 and 0.001 vs. placebo , respectively ) . The 5-mg dose of rofecoxib did not differ significantly from placebo . Patients in the rofecoxib 25- and 50-mg groups showed significant improvement in key individual efficacy measurements , including patient global assessment of pain , patient and investigator global assessment of disease activity , and Stanford Health Assessment Question naire Disability Index ( P<0.05 vs placebo ) . Compared with placebo , significantly fewer patients in the 25-mg and 50-mg rofecoxib groups discontinued therapy because of lack of efficacy ( P = 0.02 and P = 0.032 , respectively ) . Our results show that rofecoxib 25 and 50 mg once daily was effective and generally well-tolerated in patients with RA OBJECTIVE To evaluate the short-term efficacy of celecoxib , a cyclooxygenase 2-specific inhibitor , in the treatment of ankylosing spondylitis ( AS ) . METHODS The study was a 6-week r and omized , double-blind , placebo-controlled trial with 3 treatment arms : placebo , ketoprofen 100 mg twice daily , and celecoxib 100 mg twice daily . Patients who had AS according to the modified New York criteria , without peripheral synovitis and with active disease ( pain > or = 40 mm on a 100-mm visual analog scale [ VAS ] and an increase in pain of at least 30 % after nonsteroidal antiinflammatory drug withdrawal ) were eligible for study . Primary outcome measures were change in pain intensity ( VAS ) and change in functional impairment ( Bath Ankylosing Spondylitis Functional Index [ BASFI ] ) . RESULTS Of the 246 r and omized patients , 76 were allocated to receive placebo , 90 ketoprofen , and 80 celecoxib . There were no statistically significant differences between treatment groups at study entry . During the 6 weeks of the study , the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group , with a trend in favor of celecoxib when the 2 active treatments were compared . The mean changes were -13 mm , -21 mm , and -27 mm ( P = 0.006 ) for pain and 1 , -6 , and -12 ( P = 0.0008 ) for BASFI score in the placebo , ketoprofen , and celecoxib groups , respectively . During treatment , the number of patients reporting epigastric pain was 6 ( 8 % ) , 13 ( 14 % ) , and 10 ( 13 % ) in the placebo , ketoprofen , and celecoxib groups , respectively . CONCLUSION The results of this study confirm the clinical ly relevant antiinflammatory effect of celecoxib at a 200-mg daily dosage , with significant improvement of both pain and function in patients with AS To determine whether the cyclooxygenase-2 ( COX-2 ) inhibitor celecoxib affects cardiovascular thrombotic risk , we analyzed the incidence of cardiovascular events for celecoxib , placebo , and nonsteroidal anti-inflammatory drugs ( NSAIDs ) in the entire controlled , arthritis clinical trial data base for celecoxib . The primary analysis used the Antiplatelet Trialists ' Collaboration end points , which include : ( 1 ) cardiovascular , hemorrhagic , and unknown deaths , ( 2 ) nonfatal myocardial infa rct ion , and ( 3 ) nonfatal stroke . Other secondary thrombotic events were also examined . Separate analyses were performed for all patients and for those not taking aspirin . Data from all controlled , completed arthritis trials of > or = 4 weeks duration , including 13 new drug application studies and 2 large post-marketing trials ( CLASS and SUCCESS ) were included for analyses . Patients were r and omized to celecoxib at doses from 100 to 400 mg twice daily ( 18,942 patients ; 5,668.2 patient-years of exposure ) , diclofenac 50 to 75 mg twice daily , ibuprofen 800 mg thrice daily , naproxen 500 mg twice daily ( combined NSAID exposure of 11,143 patients ; 3,612.2 patient-years ) , or placebo ( 1,794 subjects ; 199.9 subject-years ) . Data from a long-term uncontrolled trial with 5,209 patients ( 6,950 patients -years ) treated with celecoxib were included in a supplemental analysis . The entire 15-trial data base was search ed for possible serious thrombotic events as well as to identify all deaths . For these patients , detailed clinical data were obtained and review ed by 2 of the investigators ( WBW and JSB ) , who were independently and blinded to exposure , to classify the event as primary , secondary , or neither . All analyses were done using the intent-to-treat population , and time-to-event analyses were performed using per-patient data . To examine heterogeneity of results among studies , tests of interaction were performed using the Cox model . Incidences of the primary and secondary events were not significantly different between the celecoxib and placebo groups , nor for the celecoxib group compared with the NSAIDs group , regardless of aspirin use and NSAID type . The relative risks comparing celecoxib with the NSAIDs for the primary events were 1.06 ( 95 % confidence interval 0.70 to 1.61 , p = 0.79 ) for all patients , and 0.86 ( 95 % confidence interval 0.48 to 1.56 , p = 0.62 ) for the subgroup not taking aspirin . Similarly , for secondary cardiovascular end points , all relative risks were < or = 1 for celecoxib compared with either placebo or NSAIDs . These comparative analyses demonstrate no evidence of increased risk of cardiovascular thrombotic events associated with celecoxib compared with either conventional NSAIDs or placebo OBJECTIVE To compare the efficacy and tolerability of the novel cyclooxygenase 2-selective inhibitor lumiracoxib with placebo and diclofenac in osteoarthritis ( OA ) . METHODS Adults ( n=583 ) with knee or hip OA were r and omized to receive for 4 weeks lumiracoxib 50 , 100 , or 200 mg twice daily or 400 mg once daily ; placebo ; or diclofenac 75 mg twice daily . Efficacy assessment s included overall joint pain intensity and Western Ontario and McMaster Universities Osteoarthritis Index subscales ; tolerability was evaluated by adverse event and physician reporting . RESULTS All lumiracoxib doses were superior to placebo in relieving pain , improving stiffness , and improving physical function after 4 weeks . At study endpoint , pain relief was comparable among all lumiracoxib dosages and similar to diclofenac . Lumiracoxib tolerability was superior to diclofenac and comparable to placebo . CONCLUSION Lumiracoxib provides predictable and sustained relief from pain , stiffness , and impaired physical function in OA . Lumiracoxib shows clinical ly comparable efficacy and superior tolerability to diclofenac OBJECTIVE This r and omized , double-blind study tested the hypothesis that rofecoxib , a drug that specifically inhibits cyclooxygenase 2 , would cause fewer gastroduodenal ulcers than ibuprofen ( in a multicenter trial ) , and its side effects would be equivalent to those of placebo ( in a prespecified analysis combining the results with another trial of identical design ) . METHODS Seven hundred seventy-five patients with osteoarthritis were r and omized to receive rofecoxib at a dosage of 25 mg or 50 mg once daily , ibuprofen 800 mg 3 times daily , or placebo . Gastroduodenal ulceration was assessed by endoscopy at 6 , 12 , and ( for active treatment ) 24 weeks . The primary and secondary end points were the incidence of gastroduodenal ulcers at 12 and 24 weeks , respectively . RESULTS Ulcers were significantly less common ( P < 0.001 ) following treatment with rofecoxib ( 25 mg or 50 mg ) than with ibuprofen after 12 weeks ( 5.3 % and 8.8 % versus 29.2 % , respectively ) or 24 weeks ( 9.9 % and 12.4 % versus 46.8 % , respectively ) . In the combined analysis , the 12-week ulcer incidence with 25 mg rofecoxib ( 4.7 % ) and with placebo ( 7.3 % ) satisfied prespecified criteria for equivalence . CONCLUSION At 2 - 4 times the therapeutically effective dose , rofecoxib caused fewer endoscopically detected ulcers than did ibuprofen . Rofecoxib at a dose of 25 mg ( the highest dose recommended for osteoarthritis ) satisfied prespecified criteria for equivalence to placebo INTRODUCTION Rofecoxib , a cyclooxygenase 2 inhibitor ( sometimes known as a specific cyclooxygenase 2 inhibitor or Coxib ) , is used in osteoarthritis ( OA ) . Published information indicates rofecoxib 's improved gastrointestinal safety profile over nonselective nonsteroidal anti-inflammatory agents ( NSAIDs ) . OBJECTIVE To evaluate the efficacy and safety of rofecoxib in treating OA in 2 studies . METHODS Two r and omized , double-blind , parallel-group studies in patients with OA of the knee or hip were conducted using identical entry criteria and end points . A 6-week placebo-controlled trial in 736 patients compared 12.5 and 25 mg of rofecoxib once daily with 800 mg of ibuprofen 3 times daily , and a 1-year study compared 12.5 and 25 mg of rofecoxib once daily with 50 mg of diclofenac 3 times daily in 693 patients . RESULTS Rofecoxib , at 12.5 and 25 mg , demonstrated efficacy clinical ly comparable with ibuprofen , assessed by 3 primary end points according to predefined comparability criteria . Both rofecoxib doses and ibuprofen provided significantly greater efficacy than placebo on all primary end points at 6 weeks . Both rofecoxib doses and diclofenac showed similar efficacy over 1 year . All treatments were well tolerated . CONCLUSIONS Rofecoxib is effective in treating OA with once-daily dosing for 6 weeks and 1 year . Rofecoxib was generally safe and well-tolerated in OA patients for 6 weeks and 1 year . Arch Fam Med . 2000;9:1124 - Context Various cyclooxygenase-2 ( COX-2 ) selective inhibitors may affect cardiovascular risk differently . Contribution This casecontrol study from 36 hospitals in a 5-county area found that reported recent use of a COX-2 selective inhibitor was similar among adults with a first , nonfatal myocardial infa rct ion ( MI ) and r and omly selected community controls with no history of MI . However , reported use of rofecoxib was associated with a 2.72 ( 95 % CI , 1.24 to 5.95 ) higher odds of MI than was use of celecoxib . Caution s About 50 % of eligible participants completed interviews . Although analyses controlled for potential confounders , recall bias and unmeasured factors related to MI risk could have affected results . The Editors Nonaspirin nonsteroidal anti-inflammatory drugs ( NSAIDs ) include those that inhibit both the cyclooxygenase-1 ( COX-1 ) isoenzyme and the COX-2 isoenzyme ( nonselective NSAIDs ) and those that are more selective for the COX-2 isoenzyme ( COX-2 selective inhibitors , herein called COX-2 inhibitors ) . Nonselective NSAIDs may reduce the risk for myocardial infa rct ion ( MI ) by inhibiting platelet aggregation ( 1 - 3 ) . On the other h and , studies have postulated that COX-2 inhibitors increase the risk for atherothrombotic events because they inhibit prostacyclin , which may increase thrombotic tendencies and vascular injury without the beneficial effect of platelet inhibition derived from COX-1 inhibition ( 4 ) . However , COX-2 inhibitors may also reduce cardiovascular risk by inhibiting vascular inflammation , improving endothelial dysfunction , and enhancing coronary plaque stability ( 5 - 8 ) . These effects may differ among COX-2 inhibitors . Along with potential differences in blood pressure effects ( 9 ) , recent evidence suggests that celecoxib and rofecoxib may differ in their effects on endothelial dysfunction and oxidative stress ( 8) . Two r and omized trials , design ed to examine risk for gastrointestinal bleeding , found different cardiovascular results with rofecoxib and celecoxib compared with their respective NSAID comparator . In the Vioxx Gastrointestinal Outcomes Research ( VIGOR ) study ( 10 ) , users of 50 mg of rofecoxib per day had a higher rate of nonfatal MI ( 11 ) than users of naproxen . In the primary analysis of the Celecoxib Long-term Arthritis Safety Study ( CLASS ) ( 12 ) , the rate of cardiovascular events did not differ between celecoxib users and ibuprofen or diclofenac users . Because these studies did not include placebo control groups , we could not determine whether these differences were due to an increased risk from rofecoxib , a decreased risk from naproxen , a combination of both , or a reduction in risk from celecoxib but not rofecoxib that balanced the potential reduction in risk from nonselective NSAIDs . Three published observational studies ( 13 - 15 ) and 2 meta-analyses ( 16 , 17 ) have assessed the risk for cardiovascular events from rofecoxib or celecoxib . The former were limited in their ability to adjust for factors that are likely to put COX-2 users at higher cardiovascular risk ( 18 ) ( for example , higher body mass index [ BMI ] and lower levels of physical activity ) , and the latter had relatively small numbers of MIs . Nonetheless , none of these studies showed an increased risk from celecoxib , whereas some , but not all , studies identified an increased risk from rofecoxib . A recent r and omized trial of meloxicam ( a relatively COX-2 selective NSAID ) compared with placebo suggested a reduction in cardiovascular outcomes with meloxicam ( 19 ) , and another trial of the COX-2 inhibitor lumiracoxib did not detect a statistically significant increase in the risk for MI ( 20 ) . Against this backdrop , a recent r and omized trial of rofecoxib , the Adenomatous Polyp Prevention on Vioxx ( APPROVe ) trial , was stopped early because of an increase in cardiovascular outcomes among rofecoxib users ( relative to placebo ) after 18 months of use , and Merck & Co. , Inc. , voluntarily withdrew rofecoxib from the worldwide market . Thus , the current data provide conflicting evidence of the potential risks and benefits of different COX-2 inhibitors , but , overall , they suggest that there may be differences between them . We sought to determine the association between COX-2 inhibitors ( specifically rofecoxib and celecoxib ) and risk for nonfatal MI . Methods Study Site and Participants The methods of our casecontrol design have been described in detail previously ( 21 ) . We design ed and powered the current study a priori to address the effects of celecoxib and rofecoxib on MI risk . We prospect ively identified case- patients as persons 40 to 75 years of age hospitalized in a 5-county region for first , nonfatal MI between May 1998 and December 2002 . Previous research has shown that almost 90 % of all case- patients identified by using these methods had verified MIs ( 21 ) . The participation rate among eligible case- patients was 55 % . We use r and om-digit dialing to select approximately 4 community controls with no history of MI from the same geographic region and during the same time period as case- patients . We chose community controls because they represent the same source population from which the cases arose and thus are the most appropriate comparison group with which to minimize the possibility of selection bias . The participation rate among known eligible controls was 50 % . We excluded the 13 valdecoxib users because no case- patients were exposed to valdecoxib and the 40 participants who used both COX-2 inhibitors and nonselective NSAIDs at the same time . The institutional review boards of the University of Pennsylvania , Philadelphia , Pennsylvania , and all participating hospitals approved the study . Data Collection and Exposure Definition We collected exposure and covariate data for all case- patients and controls by using the same structured telephone interview . Trained telephone interviewers who were not informed of the study hypothesis interviewed the patients . Case- patients were interviewed after returning home from the hospital . To maximize the validity of drug exposure information , case- patients were interviewed only if they could be reached within 4 months of their MI . Controls were interviewed within 4 months of their initial identification to prevent selection bias . To further maximize recall of use of NSAIDs ( 22 ) , case- patients and controls were prompted with indication-specific questions and examination of photographs of medications . All participants were also instructed to have all of the containers for the medications that they took during the index week ( defined later in this article ) available during the interview . We have previously shown that these methods enhanced recall of nonselective NSAID use ( 22 ) . Our previous study also suggested that case- patients recalled more than 80 % of nonselective NSAID use ( 21 ) . The a priori definition of exposure was any nonselective NSAID , COX-2 inhibitor , or aspirin use within 1 week before the index date ( the date of first onset of symptoms of MI for case- patients and the date of the telephone interview for controls ) . Participants were asked to specify the current dose of these medications . In addition , interviewers asked participants who used these medications in the index week when they began their medication in order to determine duration of use . Statistical Analysis The primary analysis focused a priori on the association of and between the 2 COX-2 inhibitors and the odds of nonfatal MI relative to no other NSAID use . We estimated differences in the odds of MI between rofecoxib and celecoxib by comparing these 2 drugs in cross-tabulations and by comparing rofecoxib with celecoxib in logistic regression that used celecoxib as the reference group . Because the effect of aspirin on platelets and MI risk ( 23 ) could modify the effects of COX-2 inhibitors , we also performed analyses separately for users and nonusers of concurrent aspirin . To adjust for confounding , we performed multiple logistic regression analyses that a priori included risk factors plus any variable that changed the odds ratio of interest by 10 % or more , with adjustment for that specific variable ( 24 ) . We considered all variables in Table 1 as potential confounders ( 25 ) . ( Adjustment for the following variables did not alter the results ; therefore , we did not include them in the multivariable models : years of education , history of renal dysfunction , rheumatoid arthritis , or osteoarthritis , income , and use of hormone replacement therapy ( among women ) . We tested interactions with COX-2 inhibitors for all variables in Table 1 by using the product term of nonsteroidal drug type by each risk factor in multivariable regression . We also examined the association of increasing frequency of COX-2 use with nonfatal MI by using the appropriate linear term for frequency in the models with nonusers included . Table 1 . Characteristics of Nonsteroidal Drug Use among Controls Analysis of COX-2 inhibitors by dosage or duration was not possible because of small numbers . Only 2 case- patients used rofecoxib , 50 mg/d ; 4 used rofecoxib , less than 25 mg/d ; 1 used celecoxib , greater than 200 mg/d ; and 3 used celecoxib , less than 200 mg/d . Thus , to examine whether differences between rofecoxib and celecoxib were due to the effects of higher dose of rofecoxib , we performed analyses after excluding patients using 50 mg of rofecoxib per day . Similarly , few case- patients used COX-2 inhibitors for less than 3 months or more than 12 months . No rofecoxib users and 2 celecoxib users reported less than 3 months of use , and only 3 rofecoxib users and 7 celecoxib users reported more than 12 months of use . Thus , to determine whether shorter ( <3 months ) or longer ( > 12 months ) duration s of medication affected the comparison between rofecoxib and celecoxib , we performed analyses after excluding those with short or long duration s of use . To determine the potential effects of recall bias , we determined the odds ratio of MI for patient-reported use of other prescription analgesics in Background : Cyclooxygenase‐2 selective inhibitors were developed in order to reduce the incidence of life‐threatening gastrointestinal ulcer complications compared with non‐selective non‐steroidal anti‐inflammatory drugs . Previous outcomes studies have , variously , lacked power to investigate this endpoint , focused on broader outcomes , or been too small to quantify the influence of aspirin BACKGROUND & AIMS The gastric safety of cyclooxgenase-2 inhibitors and prophylactic antisecretory therapy in high-risk arthritis patients is unclear . We studied the ulcer incidence and factors predicting ulcer recurrence in a prospect i ve , double-blinded trial . METHODS We studied patients who presented with nonsteroidal anti-inflammatory drug-associated ulcer bleeding . After ulcer healing , patients who were negative for Helicobacter pylori were r and omly assigned to celecoxib 200 mg twice a day plus omeprazole placebo once daily or diclofenac 75 mg twice daily plus omeprazole 20 mg once daily for 6 months . Patients underwent endoscopy if they developed recurrent bleeding . Those without recurrent events underwent endoscopy at their last follow-up visit . RESULTS Two hundred eighty-seven patients were enrolled ; 24 had recurrent gastrointestinal complications . Among 259 patients without events , 222 underwent endoscopy ( 116 received celecoxib and 106 received diclofenac plus omeprazole ) . The probability of recurrent ulcers in 6 months was 18.7 % in the celecoxib group and 25.6 % in the diclofenac plus omeprazole group ( difference , -6.7 % ; 95 % CI : -17.8 % to 3.9 % ) ( P = 0.21 ) . Combining bleeding and endoscopic ulcers , 24.1 % in the celecoxib group and 32.3 % in the diclofenac plus omeprazole group had recurrent ulcers in 6 months ( difference , -8.2 % ; 95 % CI : -19.5 % to 2.9 % ) ( P = 0.15 ) . Treatment-induced significant dyspepsia ( hazard ratio , 5.3 ; 95 % CI : 2.6 - 10.8 ) , age > or = 75 ( hazard ratio , 2.0 ; 95 % CI : 1.1 - 3.5 ) , and comorbidity ( hazard ratio , 2.1 ; 95 % CI : 1.2 - 3.7 ) independently predicted ulcer recurrence . CONCLUSIONS Among patients with previous ulcer bleeding , neither celecoxib nor diclofenac plus omeprazole adequately prevents ulcer recurrence . Treatment-induced significant dyspepsia is an indication for endoscopic evaluation OBJECTIVE To compare the incidence of gastroduodenal ulcers in patients with osteoarthritis ( OA ) treated with therapeutic doses of the novel COX-2 selective inhibitor , lumiracoxib ( COX189 , Prexige ) , and the st and ard nonsteroidal antiinflammatory drug ( NSAID ) ibuprofen . The COX-2 selective inhibitor celecoxib was included as an active control . METHODS In this r and omized , multicenter , double-blind , parallel-group study , eligible patients were r and omized to receive lumiracoxib 200 mg ( n = 264 ) or 400 mg ( n = 260 ) once daily ( qd ) , ibuprofen 800 mg ( n = 260 ) 3 times daily ( tid ) , or celecoxib 200 mg qd ( n = 258 ) for 13 weeks . The incidence of gastroduodenal ulcers and erosions was determined by endoscopy prior to r and omization , and after 4 weeks and 13 weeks of treatment ( end of study ) . Frequencies of adverse events were also recorded . RESULTS The cumulative incidence of gastroduodenal ulcers > /= 3 mm in diameter was significantly lower in the lumiracoxib groups ( 200 mg : 4.3 % ; 400 mg : 4.0 % ) than in the ibuprofen group ( 15.7 % ; p < 0.001 ) and similar to the celecoxib group ( 3.2 % ) . In the ibuprofen group , a significantly greater number of patients ( 6.0 % ) had > 10 gastroduodenal erosions compared with lumiracoxib 200 mg ( 1.2 % ; p < 0.01 ) , lumiracoxib 400 mg ( 1.6 % ; p < 0.05 ) , and celecoxib ( 2.4 % ; p < 0.05 ) . A greater number of patients in the ibuprofen group discontinued treatment due to an adverse event compared with both lumiracoxib groups and the celecoxib group . CONCLUSION In patients with OA , lumiracoxib 200 mg or 400 mg qd was associated with a significantly lower risk of gastroduodenal ulceration than ibuprofen 800 mg tid , and was similar to celecoxib 200 mg qd OBJECTIVE To evaluate the efficacy and safety of etoricoxib and indomethacin in the treatment of patients with acute gout . METHODS A r and omized , double-blind , active-comparator study was conducted at 42 sites . A total of 189 men and women ( > or = 18 years of age ) who were experiencing an acute attack ( < or = 48 hours ) of clinical ly diagnosed gout were treated for 8 days with etoricoxib , 120 mg/day ( n = 103 ) , or indomethacin , 50 mg 3 times a day ( n = 86 ) . The primary efficacy end point was the patient 's assessment of pain in the study joint ( 0 - 4-point Likert scale ) over days 2 - 5 . Safety was assessed by adverse experiences ( AEs ) occurring during the trial . RESULTS Etoricoxib demonstrated clinical efficacy comparable to that of indomethacin in terms of the patient 's assessment of pain in the study joint . The difference in the mean change from baseline over days 2 - 5 was -0.08 ( 95 % confidence interval -0.29 , 0.13 ) ( P = 0.46 ) , which fell within the prespecified comparability bounds of -0.5 to 0.5 . Secondary end points over the 8-day study , including the onset of efficacy , reduction in signs of inflammation , and patient 's and investigator 's global assessment s of response to therapy , confirmed the comparable efficacy of the two treatments . The etoricoxib-treated patients had a numerically lower incidence of AEs ( 43.7 % ) than did the indomethacin-treated patients ( 57.0 % ) and a significantly lower incidence of drug-related AEs ( 16.5 % versus 37.2 % ; P < 0.05 ) . CONCLUSION Etoricoxib at a dosage of 120 mg once daily was confirmed to be an effective treatment for acute gout . Etoricoxib was comparable in efficacy to indomethacin at a dosage of 50 mg 3 times daily , and it was generally safe and well tolerated BACKGROUND The association between the use of nonsteroidal anti-inflammatory drugs ( NSAIDs ) and acute myocardial infa rct ion ( AMI ) is unclear . Nonsteroidal anti-inflammatory drugs vary in their antithrombotic properties , with naproxen having a particularly effective antithrombotic potential . OBJECTIVE To compare the effect of naproxen vs other NSAIDs in the prevention of AMI in an older population . METHODS Population -based , matched case-control study . Patients ( aged > or = 65 years ) in Quebec had been hospitalized for AMI between January 1 , 1992 , and December 31 , 1994 . The admission date for AMI was considered the index date . Control subjects were r and omly selected from a Quebec drug and physician cl aims data base . For each case , a control was matched with the same index date , age ( within 2 years ) , and sex . Cases and controls were required to have at least 1 year of pharmaceutical and medical records before the index date to identify risk factors for AMI and exposure to naproxen or other nonaspirin NSAIDs . Concurrent exposure to a medication was defined as exposure to that medication at the index date . Logistic regression analyses were used to evaluate the association between the use of naproxen and other NSAIDs in the prevention of AMI , adjusting for potential confounders . RESULTS Included in the study were 4163 cases and 14 160 controls . Determinants ( adjusted odds ratios [ 95 % confidence intervals ] ) of AMI included use in the prior year of anticoagulants ( 0.76 [ 0.64 - 0.90 ] ) , nitrates ( 2.01 [ 1.86 - 2.17 ] ) , antidiabetic agents ( 1.72 [ 1.56 - 1.90 ] ) , antihypertensive agents ( 1.36 [ 1.28 - 1.45 ] ) , and lipid-lowering agents ( 0.83 [ 0.75 - 0.91 ] ) , as well as concurrent exposure to naproxen vs other NSAIDs ( 0.79 [ 0.63 - 0.99 ] ) . CONCLUSION Compared with other NSAIDs , concurrent exposure to naproxen has a protective effect against AMI OBJECTIVE : Etoricoxib is a selective cyclooxygenase inhibitor that in clinical studies has improved the signs and symptoms of osteoarthritis and rheumatoid arthritis and reduced the potential for GI injury . The incidence of endoscopically detected ulcers and of clinical ly important upper GI events ( perforations , ulcers , and bleeding episodes ) was compared in patients taking etoricoxib or nonselective nonsteroidal anti-inflammatory drugs ( NSAIDs ) . METHODS : Upper GI endoscopy was performed at intervals over 12 wk in 680 patients taking etoricoxib 120 mg once daily , ibuprofen 800 mg three times daily , or placebo in a r and omized , parallel-group , double-blind study . Survival analysis was used to analyze time-to-event data for the incidence of gastric or duodenal ulcers ( ≥3 mm and ≥5 mm ) , and the log rank test was used to compare the cumulative incidence between treatment groups . A combined analysis of upper GI events in all 10 Phase II/III clinical trials of etoricoxib ( 60 , 90 , or 120 mg ) versus nonselective NSAIDs ( naproxen , ibuprofen , or diclofenac ) for osteoarthritis , rheumatoid arthritis , and chronic low back pain was conducted . Investigators reported potential events for adjudication by an external , blinded committee , using prespecified criteria to confirm events . All events that occurred during active treatment periods ( maximum 792 days ) or within 14 days of stopping treatment were included in the analysis . Time to first event was evaluated using survival analysis ; the Kaplan – Meier method was used to determine the cumulative incidence , and relative risk was estimated with the Cox proportional hazards model . RESULTS : In the endoscopy study , the cumulative incidence of ulcers ≥3 mm at 12 wk in the ibuprofen group ( 17 % ) was significantly higher than in the etoricoxib group ( 8.1 % , p < 0.001 ) ; similar results were seen for ulcers ≥5 mm . In the placebo group , the rate of ulcers ≥3 mm was 1.86 % . Of 3142 patients treated with once-daily etoricoxib and 1828 patients treated with a nonselective NSAID ( ibuprofen , naproxen , or diclofenac ) , 82 patients with investigator-reported upper GI events ( 71 confirmed ) were eligible for the combined analysis . For etoricoxib versus NSAIDs , the rate per 100 patient-yr for confirmed events was 1.16 versus 3.05 ( relative risk = 0.44 , 95 % CI = 0.27–0.72 , p < 0.001 ) , whereas that for investigator-reported events was 1.35 versus 3.42 ( relative risk = 0.47 , 95 % CI = 0.30–0.74 , p = 0.001 ) . Results were driven primarily by studies with naproxen as the comparator . CONCLUSIONS : The incidence of endoscopically detected ulcers was significantly lower with etoricoxib 120 mg than with ibuprofen 2400 mg . Treatment with etoricoxib reduced the incidence of investigator-reported and confirmed adverse upper GI events by approximately 50 % compared with treatment with nonselective NSAIDs UNLABELLED We compared onset of efficacy ( during days 1 to 6 ) of 2 coxibs ( rofecoxib , celecoxib ) with acetaminophen and nabumetone by using a prespecified approach to data from 4 similarly design ed 6-week r and omized osteoarthritis trials . In 2 trials , rofecoxib ( 12.5 mg and 25 mg once daily ) was compared with celecoxib ( 200 mg once daily ) and acetaminophen ( 4000 mg daily ) . In the other 2 trials , rofecoxib ( 12.5 mg ) was compared with nabumetone ( 1000 mg once daily ) and placebo . Efficacy end points included Patient Global Response to Therapy and Western Ontario and McMaster Osteoarthritis Index scores . Rofecoxib ( 12.5- and 25-mg doses ) consistently demonstrated a faster onset of osteoarthritis ( OA ) efficacy than the comparator drugs during the first 6 days of therapy of OA patients experiencing " flare . " Acetaminophen result ed in the slowest onset of efficacy . There was a strong correlation ( 0.7 ) between efficacy response during days 1 to 6 and that averaged over 6 weeks . Rates of discontinuation as a result of lack of efficacy were significantly lower ( P < .02 ) for each of the coxib-treated groups compared with acetaminophen and for rofecoxib 12.5 mg ( P = .01 ) compared with nabumetone . Rofecoxib treatment , with its faster onset of OA efficacy and lower rates of related discontinuations , might provide efficacy advantages in the treatment of OA pain . PERSPECTIVE The efficacy of rofecoxib , celecoxib , nabumetone , and acetaminophen is established for the majority of OA patients within the first 6 days of therapy , and this predicts efficacy during the longer term . Rofecoxib provides significantly faster time to onset of efficacy and better improvement on multiple measures versus the comparators BACKGROUND Experimental studies in animals and observational studies in humans suggest that regular aspirin use may decrease the risk of colorectal adenomas , the precursors to most colorectal cancers . METHODS We conducted a r and omized , double-blind trial to determine the effect of aspirin on the incidence of colorectal adenomas . We r and omly assigned 635 patients with previous colorectal cancer to receive either 325 mg of aspirin per day or placebo . We determined the proportion of patients with adenomas , the number of recurrent adenomas , and the time to the development of adenoma between r and omization and subsequent colonoscopic examinations . Relative risks were adjusted for age , sex , cancer stage , the number of colonoscopic examinations , and the time to a first colonoscopy . The study was terminated early by an independent data and safety monitoring board when statistically significant results were reported during a planned interim analysis . RESULTS A total of 517 r and omized patients had at least one colonoscopic examination a median of 12.8 months after r and omization . One or more adenomas were found in 17 percent of patients in the aspirin group and 27 percent of patients in the placebo group ( P=0.004 ) . The mean ( + /-SD ) number of adenomas was lower in the aspirin group than the placebo group ( 0.30+/-0.87 vs. 0.49+/-0.99 , P=0.003 by the Wilcoxon test ) . The adjusted relative risk of any recurrent adenoma in the aspirin group , as compared with the placebo group , was 0.65 ( 95 percent confidence interval , 0.46 to 0.91 ) . The time to the detection of a first adenoma was longer in the aspirin group than in the placebo group ( hazard ratio for the detection of a new polyp , 0.64 ; 95 percent confidence interval , 0.43 to 0.94 ; P=0.022 ) . CONCLUSIONS Daily use of aspirin is associated with a significant reduction in the incidence of colorectal adenomas in patients with previous colorectal cancer OBJECTIVE To compare the clinical efficacy of rofecoxib , a specific inhibitor of cyclooxygenase 2 ( COX-2 ) , with that of diclofenac in patients with osteoarthritis ( OA ) and to evaluate the safety and tolerability of rofecoxib . METHODS We performed a r and omized , double-blind , active comparator-controlled trial in 784 adults with OA of the knee or hip . Patients were r and omized to 1 of 3 treatment groups : 12.5 mg of rofecoxib once daily , 25 mg of rofecoxib once daily , and 50 mg of diclofenac 3 times daily . Clinical efficacy and safety were evaluated over a 1-year continuous treatment period . RESULTS Rofecoxib at dosages of 12.5 and 25 mg demonstrated efficacy that was clinical ly comparable to that of diclofenac , as assessed by all 3 primary end points according to predefined comparability criteria . Results from secondary end points were consistent with those of the primary end points . There were small statistical differences favoring diclofenac for 2 of the end points . All treatments were well tolerated . CONCLUSION Rofecoxib was well tolerated and provided efficacy that was clinical ly comparable , according to predefined statistical criteria , to that of 150 mg of diclofenac per day in this 1-year study . Specific inhibition of COX-2 provided therapeutic efficacy in OA SUMMARY Objective : We recently reported the efficacy of rofecoxib in two r and omized controlled trials in chronic low back pain ( CLBP ) . The objectives of this report are to present data regarding the onset of efficacy of rofecoxib from these trials and propose methods for reporting onset . Research design and methods : Patients were aged 18 - 75 , with non-radicular CLBP for > 3 months . Patients were r and omized to rofecoxib 25 mg , 50 mg , or placebo once daily for 4 weeks . Assessment s included Low Back Pain and Bothersomeness scales every morning and Relief from Starting Pain after the first dose at 0.5,1 , 2 , 3,4h , bedtime , and next morning . Onset of meaningful relief was measured by Time to Confirmed 50 % Reduction in Pain and Time to Confirmed ' Slightly ' or ' Not At All ' Bothersome Pain . Onset of perceptible pain relief was measured by Time to At Least ' A Little ' Confirmed Pain Relief . Results : 690 patients entered . Significantly more patients treated with rofecoxib had meaningful relief compared to placebo : 60.4,58.4 , and 34.7 % for rofecoxib 25 mg , 50 mg , and placebo ( p < 0.001 ) . Median time to meaningful relief for rofecoxib was 2 days , 1 day sooner than placebo . Rofecoxib was superior to placebo by bedtime after the first dose . Conclusions : Approximately 2/3 of patients achieved meaningful pain relief with rofecoxib compared with 1/3 receiving placebo . Median time to onset of meaningful relief was about 2 days , but superior relief over placebo was seen by bedtime after the first dose . Onset of perceptible pain relief was within 2 h. We propose that measures of onset of analgesic effect include the proportion of patients who achieve meaningful pain relief and in this subgroup , the time-to-onset of confirmed meaningful reduction in pain intensity , time-to-onset of confirmed pain relief , and time to first separation from placebo in the proportion of patients who achieve meaningful pain relief OBJECTIVES This study was design ed to determine if non-aspirin non-steroidal anti-inflammatory drugs ( NANSAIDs ) are associated with lower odds of myocardial infa rct ion ( MI ) and if NANSAIDs , particularly ibuprofen , interfere with aspirin 's cardioprotective effect . BACKGROUND The NANSAIDs may reduce the risk of MI but may also interfere with aspirin 's cardioprotective effect . METHODS A case-control study was conducted , with cases of first , nonfatal MI identified prospect ively and controls identified r and omly from the community . RESULTS The use of NANSAIDs was associated with a significant reduction in MI among those not using aspirin ( adjusted odds ratio [ OR ] 0.53 ; 95 % confidence interval [ CI ] : 0.42 to 0.67 ) . This was true for both ibuprofen ( adjusted OR 0.52 ; 95 % CI : 0.39 to 0.69 ) and naproxen ( adjusted OR 0.48 ; 95 % CI : 0.28 to 0.82 ) . Although aspirin itself was associated with decreased odds of MI in those not also using NANSAIDs ( adjusted OR relative to no aspirin use 0.79 ; 95 % CI : 0.63 to 0.98 ) , it was not associated with decreased odds of MI among those who were using NANSAIDs ( OR 1.28 ; 95 % CI : 0.85 to 1.94 ; p value for interaction = 0.026 ) . The association of aspirin and reduced odds of MI diminished with increasing frequency of NANSAID use ( test for interaction p = 0.006 ) , particularly for ibuprofen ( p = 0.018 ) . Among frequent ( 4 times/week ) NANSAID users , the OR for aspirin versus no aspirin was 2.04 ( 95 % CI : 1.06 to 3.94 ) . Users of prophylactic aspirin plus frequent ibuprofen had an OR relative to aspirin-only users of 2.03 ( 95 % CI : 0.60 to 6.84 ) . CONCLUSIONS In the absence of aspirin use , NANSAIDs are associated with reduced odds of MI . In those using aspirin , NANSAIDs do not provide additional protection . Additional study is needed to determine the clinical impact of using NANSAIDs along with aspirin for cardioprotection OBJECTIVE A clinical trial was conducted in 600 patients with OA of the knee to test the hypothesis that the specific COX-2 inhibitor , celecoxib , has equivalent efficacy and a superior tolerability/safety profile when compared to diclofenac , the current worldwide st and ard of care . METHODS Patients were administered celecoxib 100 mg BID , diclofenac 50 mg TID or placebo for 6 weeks in a multicentre , double-blind . placebo-controlled trial . RESULTS Primary efficacy measures ( index joint pain by VAS , WOMAC index ) indicated statistically significant improvement versus placebo for both celecoxib and diclofenac and no statistically significant differences between celecoxib and diclofenac . American Pain Society ( APS ) measures to assess the rapidity of onset of action showed statistically significant and comparable pain relief versus placebo within 24 h for both celecoxib and diclofenac . More diclofenac patients reported GI side effects than patients treated with either placebo or celecoxib . Diclofenac-treated patients experienced statistically significant elevations in mean hepatic transaminases and serum creatinine and reductions in haemoglobin concentration when compared to placebo , events not observed with celecoxib . CONCLUSION Celecoxib 200 mg daily is as effective as diclofenac 150 mg daily for relieving signs and symptoms of OA of the knee , including pain , and has a rapid onset of action . However , celecoxib appears to have a superior safety and tolerability profile OBJECTIVE We compared the efficacy and upper gastrointestinal safety of the cyclooxygenase-2-specific inhibitor valdecoxib with naproxen and placebo in treating moderate to severe osteoarthritis of the knee . STUDY DESIGN This multicenter , r and omized , double-blind , placebo-controlled study compared the efficacy and upper gastrointestinal tract safety of valdecoxib at dosages of 5 , 10 , and 20 mg once daily with placebo and naproxen at the dosage of 500 mg twice daily . POPULATION We included patients who had been diagnosed with moderate to severe osteoarthritis of the knee according to the modified criteria of the American College of Rheumatology . OUTCOMES MEASURED The Patient 's and Physician 's Global Assessment of Arthritis ( PaGAA , PhGAA ) , Patient 's Assessment of Arthritis Pain-Visual Analog Scale ( PAAP-VAS ) , and Western Ontario and McMaster 's Universities ( WOMAC ) Osteoarthritis indices were assessed at baseline and at weeks 2 , 6 , and 12 . Upper gastrointestinal ulceration was assessed by pre- and posttreatment endoscopies . RESULTS Valdecoxib 10 and 20 mg once daily ( but not 5 mg once daily ) demonstrated similar efficacy to naproxen at 500 mg twice daily , and all 3 dosages were superior to placebo for the PaGAA , PhGAA , PAAP-VAS , and WOMAC Osteoarthritis indices at most assessment s throughout the 12-week study ( P < .05 ) . The incidence of endoscopically proven ulcers was significantly higher in the naproxen group than in the 5- and 10-mg valdecoxib groups , but not in the 20-mg valdecoxib group . All 3 valdecoxib doses were comparable to placebo in ulcer incidence . CONCLUSIONS Valdecoxib ( 10 and 20 mg once daily ) is significantly superior to placebo and as effective as naproxen ( 500 mg twice daily ) in improving moderate to severe osteoarthritis of the knee . Upper gastrointestinal tract safety of valdecoxib ( 5 and 10 mg ) was comparable to that of placebo and significantly better than that of naproxen |
12,478 | 22,112,442 | Until now , there 's no clear statistical evidence for the use of either TTV or nodal volume versus primary tumor volume to predict the individual loco-regional control or survival after treatment . | This systematic review addresses the prognostic significance of neck node volume in head and neck cancer .
Primary tumor volume evolved as an independent significant factor for survival in head and neck cancer patients .
Besides primary tumor volume , multiple prognostic features related to the regional lymph nodes were studied in literature .
In literature , some authors showed the significance of total tumor volume/nodal volume for survival and loco-regional control . | PURPOSE To identify prognostic clinical and treatment related factors for local control , distant metastasis-free survival , and survival by means of a multivariate analysis in patients with advanced squamous cell carcinoma of the head and neck after concomitant boost radiochemotherapy . PATIENTS AND METHODS From 1992 to 1995 , 68 patients with squamous cell cancer of the head and neck ( 93 % stage IV disease ) were treated with a simultaneous radiochemotherapy with Carboplatin using a concomitant boost technique . The total tumor volume ( TTV ) was quantitatively determined based on computed tomography scans in 56 patients . A Cox proportional hazards regression analysis was performed for each of the above endpoints and statistical significance of the Cox models was verified using the likelihood ratio test and Bonferroni correction for multiple testing . RESULTS The survival and locoregional control rates at three years were 35 and 32 % . The multivariate analysis revealed a significant association between the TTV and survival ( P = 0.0008 ) and between the pretreatment serum hemoglobin concentration and locoregional control ( P = 0.01 ) and survival ( P = 0.05 ) . The locoregional control was significantly associated with the N-stage ( P = 0.007 ) and there was a good correlation between the N-stage and TTV in this study population . CONCLUSION Our data corroborate the prognostic relevance of the tumor volume and hemoglobin concentration . In studies comparing the survival of patients with advanced cancer of the head and neck , the use of the TTV as a covariable may improve the statistical power In trial no. 22811 on a r and omized comparison of multiple fractions per day ( MFD ) , with or without misonidazole , to conventional fractionation in advanced head and neck cancer , a large number ( 523 ) of patients was entered in a short period of time . No differences in treatment results were obtained , but the study created an important data base , allowing for detailed evaluation of the most important factors influencing prognosis . In univariate analysis , factors significantly influencing survival and locoregional control were : performance status , histological differentiation , tumor site , tumor and nodal staging , and tumoral and nodal volume . In multivariate analysis , significant factors for survival were nodal involvement , tumor stage , performance status , and tumor site . Significant factors for locoregional control were nodal involvement and total tumor burden . This analysis suggests that total tumor burden ( volume ) should be included in the interpretation of treatment results in head and neck cancer Purpose : Tumor volume after the lymph node involvement is one of the most important single prognostic factor in patients of head and neck cancers treated with radiotherapy . We have recently demonstrated that the hypoxic subvolume is more important than the total tumor volume . We therefore propose the hypothesis that the presence of visible necrosis might be an important factor for cure by radiotherapy in squamous cell cancers of the head and neck . Methods : A total of 51 patients with locally advanced inoperable ( T3 - 4 or N2 - 3 ) squamous cell cancers of the head and neck ( mean age 57 years , range 41–75 years ) were prospect ively investigated with regard to a possible impact of tumor volume . All patients received CT examination of the head and neck according to a st and ardized protocol ( spiral CT , contrast enhancement after automatic injection ) , and the total tumor volume was calculated as the sum of volumes of all visible macroscopic tumor sites . Poorly perfused and necrotic areas ( no contrast enhancement ) within macroscopic tumor sites were also calculated . Patients were then treated with accelerated-hyperfractionated radiotherapy in about 6 weeks . Seventeen patients were treated with only radiation . Patients without contraindications to cisplatin chemotherapy received cisplatin chemotherapy or a combination of cisplatin and paclitaxel ( N=34 ) . The allocation of patients to certain treatment regimens was based on individual decisions in each case and not r and omized . Results : In patients treated with radiation alone , 12/17 ( 71 % ) got recurrence whereas in patients treated with radiation plus cisplatin , only 14/34 ( 41 % ) recurred ( P=0.05 ) . The 2-year overall survival was for radiation alone versus radiation plus cisplatin 0 % vs. 62 % ( P<0.0008 ) . Tumors with smaller amount of necrosis ( necrosis volume<4 cm3 ) had a good prognosis irrespective of type of treatment ( radiation alone or radiation plus cisplatin ) . However , patients with tumors with a larger amount of necrosis ( necrosis volume≥4 cm3 ) had a significantly better outcome if they were treated with radiation plus cisplatin as compared to patients treated with radiation alone . In a multi-variate analysis using a Cox-regression model the type of treatment ( radiotherapy plus versus without cisplatin ) was the only independent prognostic factor for event-free survival ( P<0.03 ) in the whole group . Conclusions : In this non-r and omized retrospective investigation with limited sample size , radiation plus cisplatin was superior to radiation alone . This result ed mainly from a higher efficacy of the radiochemotherapy regimen in patients with large and especially necrotic tumors . The prognostic and predictive impact of visible necrosis should be further evaluated PURPOSE To determine whether the immunohistochemical expression of proliferation-associated antigens ( proliferating cell nuclear antigen , MIB1 ) and the nuclear p53 reactivity in addition to total tumor volume , nodal CT density and T and N category are predictive for overall survival and locoregional tumor control in patients with squamous cell carcinoma of the head and neck region . MATERIAL S AND METHODS Between October 1989 and September 1993 , 87 patients with biopsy proven head and neck cancer were r and omly allocated to receive radiation alone or simultaneous radiation and chemotherapy as part of a multicenter trial with a total of 298 r and omized patients . There were only inoperable lesions in UICC ( 1992 ) stage III ( 8 % ) and IV ( 92 % ) . Radiotherapy was delivered with 180 cGy twice daily up to a total dose of 7020 cGy in 51 days . Three cycles of 2340 cGy each were separated by a rest period of 11 days . Chemotherapy consisted of cis-DDP , 5-fluorouracil and leucovorin and was repeated on days 22 and 44 . Routinely-processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferation-associated antigens ( MIB1 and PCNA ) and p53 oncoprotein to determine the labeling index ( LI ) . In addition , the total tumor volume and the percentage of necrosis were measured using CT data . The median follow-up was 3.9 years ( range 1.9 - 5.0 years ) . RESULTS The overall survival and locoregional control for all 87 patients were 34 and 39 % at 3 years , respectively . The addition of chemotherapy result ed in a better overall survival ( 27 versus 47 % , P = 0.03 ) but did not influence locoregional control ( 31 versus 47 % , P = 0.08 ) . In univariate analysis , nodal CT density ( P < 0.0001 ) , total tumor volume ( P < 0.0001 ) , age ( P = 0.001 ) and the MIB1-LI ( P = 0.04 ) had a significant impact on overall survival . However , in the final Cox model only the nodal CT density ( P = 0.0003 ) and age ( P = 0.05 ) were independent prognostic factors for survival and only the nodal CT density ( P = 0.0006 ) was an independent prognostic factor for locoregional control . The expression of the p53 oncoprotein was not found to have a clear predictive value . CONCLUSION Nodal CT density , total tumor volume and age will remain the relevant prognostic factors in stage III/IV head and neck cancer The imaging and analysis protocol of the UK multicentre study of magnetic resonance imaging ( MRI ) as a method of screening for breast cancer in women at genetic risk is described . The study will compare the sensitivity and specificity of contrast-enhanced MRI with two-view x-ray mammography . Approximately 500 women below the age of 50 at high genetic risk of breast cancer will be recruited per year for three years , with annual MRI and x-ray mammography continuing for up to 5 years . A symptomatic cohort will be measured in the first year to ensure consistent reporting between centres . The MRI examination comprises a high-sensitivity three-dimensional contrast-enhanced assessment , followed by a high-specificity contrast-enhanced study in equivocal cases . Multiparametric analysis will encompass morphological assessment , the kinetics of contrast agent uptake and determination of quantitative pharmacokinetic parameters . Retrospective analysis will identify the most specific indicators of malignancy . Sensitivity and specificity , together with diagnostic performance , diagnostic impact and therapeutic impact will be assessed with reference to pathology , follow-up and changes in diagnostic certainty and therapeutic decisions . Mammography , lesion localisation , pathology and cytology will be performed in accordance with the UK NHS Breast Screening Programme quality assurance st and ards . Similar st and ards of quality assurance will be applied for MR measurements and evaluation PURPOSE To investigate the value of CT-derived tumor parameters as predictor of local and regional outcome of tonsillar squamous cell carcinoma treated by definitive radiation therapy . METHODS AND MATERIAL S The pretreatment CT studies of 112 patients with tonsillar squamous cell carcinoma were review ed . After redigitizing the films , primary and nodal tumor volume was calculated with the summation-of- areas technique . The nodal CT aspect was grade d using a 3-point scale ( homogenous , inhomogeneous , and necrotic ) . Mean follow-up time was 33 months . Actuarial statistical analysis of local and regional outcome was done for each of the covariates ; multivariate analysis was performed using Cox 's proportional hazards model . RESULTS In the actuarial analysis , CT-determined primary tumor volume was significantly correlated with local recurrence rate ( p < 0.05 ) when all patients were considered , but primary tumor volume did not predict local control within the T2 , T3 , and T4 category . CT-determined nodal volume was significantly related to regional outcome ( p < 0.01 ) , but nodal density was not . Total tumor volume was not significantly related to locoregional outcome ( p = 0.1 ) . In the multivariate analysis , the T and N categories were the independent predictors of local and regional outcomes , respectively . CONCLUSION Compared to other head- and -neck sites , primary and nodal tumor volume have only marginal predictive value regarding local and regional outcome after radiation therapy in tonsillar cancer PURPOSE Tumor volume ( TV ) is one of the main reported factors determining the outcome of treatment in head- and -neck carcinomas . In this study , the prognostic impact of TV was explored in the context of a r and omized trial with the patients assigned to receive st and ard radiotherapy ( RT ) alone or RT plus platinum compounds ( RT alone , RT plus cisplatin , or RT plus carboplatin ) . METHODS AND MATERIAL S The tumor outlines were traced and digitized on each pretreatment CT slice for each of the 101 patients studied . Taking into account the magnification factor of the scan and CT slice thickness , a computer with specifically design ed software calculated the TV in cubic centimeters . RESULTS The median overall survival for the whole group of patients was 21.6 months ( 95 % confidence interval , 13.0 - 30.2 ) and the 3-year survival rate was 40 % . The addition of platinum compounds to RT ( Groups 2 and 3 ) significantly improved the survival rate ( RT alone vs. RT plus cisplatin , hazard ratio 0.36 , p = 0.002 ; RT alone vs. RT plus carboplatin , hazard ratio 0.53 , p = 0.029 ) . In univariate analysis , the most significant parameters for survival were treatment group , total gross tumor volume ( TGTV ) , complete response , nodal GTV , primary GTV , and performance status . In multivariate analysis , treatment group , TGTV , gender , and primary site were independent prognostic factors for survival . A prognostic threshold of 22.8 cm(3 ) was detected for TGTV . Patients with a TGTV of < 22.8 cm(3 ) were more likely to achieve a complete response and had a median survival of 45.3 months , and those with a TGTV > 22.8 cm(3 ) had a median survival of 12.3 months ( log-rank test , p = 0.0102 ) . CONCLUSION The prognostic significance of the TGTV was confirmed and a cutoff value of 22.8 cm(3 ) derived . Our data indicated that locally advanced head- and -neck carcinomas should not be treated by st and ard ( once-daily ) RT alone . Tumor size and disease subsite should be taken into account in future r and omized trials to increase their statistical power OBJECTIVES /HYPOTHESIS Just as tumor volume is a prognostic indicator for local disease control among patients with head and neck cancer of intermediate size treated with radiation therapy , we hypothesized a similar association for patients with advanced disease treated with chemoradiation therapy . STUDY DESIGN Retrospective analysis of primary and nodal tumor volume was correlated with prospect ively collected treatment outcome measures . METHODS Sixty-four patients with stage III-IV disease who were treated with targeted intra-arterial chemotherapy and radiation therapy ( RADPLAT ) were studied . Tumor volume was correlated with local disease control and survival . RESULTS Primary tumor volume correlated with local disease control and survival . The greatest risk for local failure was found among patients with primary tumor volume greater than 19.6 cc ( 93.8 % vs. 57 % [ P = .001 ] ) . A nominal logistic regression analysis demonstrated primary tumor volume as being the only significant parameter related to local failure . Survival was only 14.1 % among patients with primary tumor volume greater than 19.6 cc compared with 41.5 % for patients with volumes less than 19.6 cc ( P=.0018 ) . A proportional hazard model indicated that the most significant and independent parameters associated with survival were primary tumor volume ( P=.0007 ) and the site of the tumor ( P=.05 ) . CONCLUSION Tumor volume is the most important factor predictive of treatment outcome among patients with advanced head and neck cancer and should be used to stratify favorable versus unfavorable patient subsets |
12,479 | 24,833,028 | AUTHORS ' CONCLUSIONS Early PCV , either before or after RT , appears to improve OS of participants with AO or AOA .
Use of biomarkers including codeletion of chromosomes 1p and 19q with or without IDH-1 or -2 mutation identify a subset of people with increased sensitivity to combined PCV and RT .
However , PCV was associated with significant grade 3 and 4 toxicities , and whether temozolomide can be substituted for this remains unclear | BACKGROUND St and ard care of adjuvant treatment for anaplastic oligodendrogliomas ( AO ) and anaplastic oligoastrocytomas ( AOA ) is not yet well defined .
The benefit of adjuvant chemotherapy and radiotherapy ( RT ) , given as single modalities or sequentially , is still unclear .
Furthermore , insight into the predictive and prognostic impact of various biomarkers is surging .
OBJECTIVES To compare postoperative sequential RT and chemotherapy to RT alone in adults with newly diagnosed AO or mixed AOA .
To evaluate the predictive and prognostic impact of the following biomarkers : codeletion of chromosomes 1p and 19q , O(6)-methylguanine-DNA methyltransferase ( MGMT ) promotor methylation and isocitrate dehydrogenase (IDH)-1 and -2 mutations . | Despite similar morphological aspects , anaplastic oligodendroglial tumors ( AOTs ) form a heterogeneous clinical subgroup of gliomas . The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas . To identify new genomic regions associated with prognosis , 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization . The data were processed using a binary tree method . Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis ( p < 0.0001 ) . Type I tumors ( 25 % ) were characterized by : ( 1 ) an EGFR amplification , ( 2 ) a poor prognosis , ( 3 ) a higher rate of necrosis , and ( 4 ) an older age of patients . Type II tumors ( 21.7 % ) had : ( 1 ) loss of prognostic BACs located on 1p tightly associated with 19q deletion , ( 2 ) a longer survival , ( 3 ) an oligodendroglioma phenotype , and ( 4 ) a frontal location in brain . Type III AOTs ( 11.7 % ) exhibited : ( 1 ) a deletion of prognostic BACs located on 21q , and ( 2 ) a short survival . Finally , type IV tumors ( 41.7 % ) had different genomic patterns and prognosis than type I , II and III AOTs . Multivariate analysis showed that genomic type provides additional prognostic data to clinical , imaging and pathological features . Similar results were obtained in the cohort of 45 central ly review ed – vali date d cases of AOTs . Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs PURPOSE This is one of a few studies that have explored the value of baseline symptoms and health-related quality of life ( HRQOL ) in predicting survival in patients with brain cancer . PATIENTS AND METHODS Baseline HRQOL scores ( from the European Organisation for Research and Treatment of Cancer [ EORTC ] Quality of Life Question naire C30 and the EORTC Brain Cancer Module ) were examined in 247 patients with anaplastic oligodendrogliomas to determine the relationship with overall survival by using Cox proportional hazards regression models . Refined techniques as the bootstrap resampling procedure and the computation of C indexes and R2 coefficients were used to explore the stability of the models as well as better assess the potential benefit of using HRQOL to predict survival in clinical practice and research . RESULTS Classical analysis controlled for major clinical prognostic factors selected emotional functioning ( P = .0016 ) , communication deficit ( P = .0261 ) , future uncertainty ( P = .0481 ) , and weakness of legs ( P = .0001 ) as statistically significant prognostic factors of survival . However , several issues question the validity of these findings and no single model was found to be preferable over all others . C indexes , which estimate the probability of a model to correctly predict which patient among a r and omly chosen pair of patients will survive longer , and R2 coefficients , which measure the proportion of variability explained by the model , did not exhibit major improvement when adding selected or all HRQOL scores to clinical factors . CONCLUSION While classical techniques lead to positive results , more refined analyses suggest that baseline HRQOL scores add relatively little to clinical factors to predict survival . These results may have implication s for future use of HRQOL as a prognostic factor for patients with cancer PURPOSE O6-methylguanine-methyltransferase ( MGMT ) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy ( RT ) . It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine , lomustine , and vincristine ( PCV ) chemotherapy in patients with anaplastic oligodendroglial tumors ( AOT ) . PATIENTS AND METHODS In the European Organisation for the Research and Treatment of Cancer study 26951 , 368 patients with AOT were r and omly assigned to either RT alone or to RT followed by adjuvant PCV . From 165 patients of this study , formalin-fixed , paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis . This was investigated with methylation specific multiplex ligation-dependent probe amplification . RESULTS In 152 cases , an MGMT result was obtained , in 121 ( 80 % ) cases MGMT promoter methylation was observed . Methylation strongly correlated with combined loss of chromosome 1p and 19q loss ( P = .00043 ) . In multivariate analysis , MGMT promoter methylation , 1p/19q codeletion , tumor necrosis , and extent of resection were independent prognostic factors . The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival . In tumors diagnosed at central pathology review as glioblastoma , no prognostic effect of MGMT promoter methylation was observed . CONCLUSION In this study , on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy . The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The increased chemosensitivity of oligodendroglial tumors has been associated with loss of heterozygosity ( LOH ) on chromosomes 1p and 19q . Other clinical and molecular factors have also been identified as being prognostic and predictive for treatment outcome . Seventy-seven patients with anaplastic oligodendroglioma ( AO ) or anaplastic oligoastrocytoma ( AOA ) , treated in Beijing Tiantan Hospital from 2006 through 2008 , were review ed . LOH 1p , LOH 19q , IDH1 mutation , O(6)-methylguanine-DNA methyltransferase ( MGMT ) promoter methylation , and protein expression level of MGMT , P53 , EGFR , and Ki-67 were evaluated . Age at diagnosis , LOH 1p and 19q , IDH1 mutation , P53 expression level , reoperation when progression , and adjuvant chemotherapy were statistically significant factors for overall survival ( OS ) in univariate analysis . Further multivariate analysis showed that age at diagnosis ( P = .010 ) , LOH 1p and 19q ( P = .016 ) , IDH1 mutation ( P = .011 ) , and reoperation after progression ( P = .048 ) were independent predictors for longer survival in these patients . Nonr and om associations were found between LOH 1p and LOH 19q , MGMT promoter methylation and LOH 1p or 19q , IDH1 mutation and LOH 1p and 19q , IDH1 mutation and MGMT promoter methylation , whereas mutual exclusion was found between MGMT promoter methylation and MGMT expression level . The present study confirmed that age at diagnosis , LOH 1p and 19q , IDH1 mutation , and reoperation after progression were independent significant prognostic factors for patients with anaplastic oligodendroglial tumors . Inter-relationship between LOH 1p , LOH 19q , IDH1 mutation , MGMT promoter methylation , and MGMT expression level were also revealed . Future clinical trials for AO and AOA should consider the molecular alterations of patients PURPOSE The st and ard of care for anaplastic gliomas is surgery followed by radiotherapy . The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas . PATIENTS AND METHODS Patients ( N = 318 ) were r and omly assigned 2:1:1 ( A : B1:B2 ) to receive conventional radiotherapy ( arm A ) ; procarbazine , lomustine ( CCNU ) , and vincristine ( PCV ; arm B1 ) ; or temozolomide ( arm B2 ) at diagnosis . At occurrence of unacceptable toxicity or disease progression , patients in arm A were treated with PCV or temozolomide ( 1:1 r and om assignment ) , whereas patients in arms B1 or B2 received radiotherapy . The primary end point was time to treatment failure ( TTF ) , defined as progression after radiotherapy and one chemotherapy in either sequence . RESULTS Patient characteristics in the intention-to-treat population ( n = 274 ) were balanced between arms . All histologic diagnoses were central ly confirmed . Median TTF ( hazard ratio [ HR ] = 1.2 ; 95 % CI , 0.8 to 1.8 ) , progression-free survival ( PFS ; HR = 1.0 ; 95 % CI , 0.7 to 1.3 , and overall survival ( HR = 1.2 ; 95 % CI , 0.8 to 1.9 ) were similar for arms A and B1/B2 . Extent of resection was an important prognosticator . Anaplastic oligodendrogliomas and oligoastrocytomas share the same , better prognosis than anaplastic astrocytomas . Hypermethylation of the O(6)-methylguanine DNA-methyltransferase ( MGMT ) promoter ( HR = 0.59 ; 95 % CI , 0.36 to 1.0 ) , mutations of the isocitrate dehydrogenase ( IDH1 ) gene ( HR = 0.48 ; 95 % CI , 0.29 to 0.77 ) , and oligodendroglial histology ( HR = 0.33 ; 95 % CI , 0.2 to 0.55 ) reduced the risk of progression . Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm . CONCLUSION Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas . IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas , with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation Purpose : Recent studies have shown the prognostic significance of IDH1 mutations in glioma . It is yet unclear if IDH1 mutations are predictive for outcome to chemotherapy . We determined the effect of IDH1 mutations on progression-free survival and overall survival ( OS ) , and its correlation with other clinical and molecular features in the prospect i ve r and omized European Organization for Research and Treatment of Cancer study 26951 on adjuvant procarbazine , 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea , and vincristine ( PCV ) in anaplastic oligodendroglioma . Experimental Design : IDH1 and IDH2 alterations of the mutational hotspot codons R132 and R172 were assessed by the bidirectional cycle sequencing of PCR-amplified fragments . MGMT promoter methylation was assessed using methylation-specific multiplex ligation – dependant probe amplification based on methylation-sensitive restriction analysis . Loss of chromosomes 1p , 19q , 10 , and 10q and the gain of 7 and the EGFR gene were assessed with fluorescence in situ hybridization . Results : From 159 patients , sufficient material was available for IDH1 analysis . In 151 and 118 of these patients , respectively , the 1p/19q status and the MGMT promoter methylation status were known . In 73 cases ( 46 % ) , an IDH1 mutation was found and only one IDH2 mutation was identified . The presence of IDH1 mutations correlated with 1p/19q codeletion and MGMT promoter methylation , and inversely correlated with loss of chromosome 10 , EGFR amplification , polysomy of chromosome 7 , and the presence of necrosis . IDH1 mutations were found to be prognostic in the radiotherapy- and the radiotherapy/PCV-treated patients , for both progression-free survival and OS . With Cox proportional hazard modeling for OS with stepwise selection , IDH1 mutations and 1p/19q codeletion but not MGMT promoter methylation were independent prognostic factors . Conclusion : In this homogeneously treated group of anaplastic oligodendroglioma patients , the presence of IDH1 mutations was found to carry a very strong prognostic significance for OS but without evidence of a predictive significance for outcome to PCV chemotherapy . IDH1 mutations were strongly associated with 1p/19q codeletion and MGMT promoter methylation . Clin Cancer Res ; 16(5 ) ; Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas , oligodendrogliomas and oligoastrocytomas of WHO grade s II and III . IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in these tumors , albeit at much lower frequencies . Preliminary data suggest an importance of IDH1 mutation for prognosis showing that patients with anaplastic astrocytomas , oligodendrogliomas and oligoastrocytomas harboring IDH1 mutations seem to fare much better than patients without this mutation in their tumors . To determine mutation types and their frequencies , we examined 1,010 diffuse gliomas . We detected 716 IDH1 mutations and 31 IDH2 mutations . We found 165 IDH1 ( 72.7 % ) and 2 IDH2 mutations ( 0.9 % ) in 227 diffuse astrocytomas WHO grade II , 146 IDH1 ( 64.0 % ) and 2 IDH2 mutations ( 0.9 % ) in 228 anaplastic astrocytomas WHO grade III , 105 IDH1 ( 82.0 % ) and 6 IDH2 mutations ( 4.7 % ) in 128 oligodendrogliomas WHO grade II , 121 IDH1 ( 69.5 % ) and 9 IDH2 mutations ( 5.2 % ) in 174 anaplastic oligodendrogliomas WHO grade III , 62 IDH1 ( 81.6 % ) and 1 IDH2 mutations ( 1.3 % ) in 76 oligoastrocytomas WHO grade II and 117 IDH1 ( 66.1 % ) and 11 IDH2 mutations ( 6.2 % ) in 177 anaplastic oligoastrocytomas WHO grade III . We report on an inverse association of IDH1 and IDH2 mutations in these gliomas and a non-r and om distribution of the mutation types within the tumor entities . IDH1 mutations of the R132C type are strongly associated with astrocytoma , while IDH2 mutations predominantly occur in oligodendroglial tumors . In addition , patients with anaplastic glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations PURPOSE Anaplastic oligodendroglioma are chemotherapy-sensitive tumors . We now present the long-term follow-up findings of a r and omized phase III study on the addition of six cycles of procarbazine , lomustine , and vincristine ( PCV ) chemotherapy to radiotherapy ( RT ) . PATIENTS AND METHODS Adult patients with newly diagnosed anaplastic oligodendroglial tumors were r and omly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV . An exploratory analysis of the correlation between 1p/19q status and survival was part of the study . Retrospectively , the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase ( IDH ) gene were determined . The primary end points were overall survival ( OS ) and progression-free survival based on intent-to-treat analysis . RESULTS A total of 368 patients were enrolled . With a median follow-up of 140 months , OS in the RT/PCV arm was significantly longer ( 42.3 v 30.6 months in the RT arm , hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.60 to 0.95 ) . In the 80 patients with a 1p/19q codeletion , OS was increased , with a trend toward more benefit from adjuvant PCV ( OS not reached in the RT/PCV group v 112 months in the RT group ; HR , 0.56 ; 95 % CI , 0.31 to 1.03 ) . IDH mutational status was also of prognostic significance . CONCLUSION The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors . 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non-1p/19q-deleted tumors PURPOSE A recent report suggests that alterations of chromosome arms 1p and 19q are associated with chemotherapeutic response and overall survival in anaplastic oligodendroglioma patients treated with procarbazine , lomustine , and vincristine chemotherapy . We set out to further clarify the diagnostic and prognostic implication s of these alterations in a broader set of diffuse gliomas , including astrocytic neoplasms and low- grade oligodendrogliomas . PATIENTS AND METHODS Fluorescence in situ hybridization ( FISH ) signals from DNA probes mapping to 1p and 19q common deletion regions were enumerated in 162 diffuse gliomas ( 79 astrocytomas , 52 oligodendrogliomas , and 31 mixed oligoastrocytomas ) , collected as part of an ongoing prospect i ve investigation of CNS tumors . RESULTS The oligodendroglial phenotype was highly associated with loss of 1p ( P = .0002 ) , loss of 19q ( P < .0001 ) , and combined loss of 1p and 19q ( P < .0001 ) . Combined loss of 1p and 19q was identified as a univariate predictor of prolonged overall survival among patients with pure oligodendroglioma ( log-rank , P = .03 ) and remained a significant predictor after adjusting for the effects of patient age and tumor grade ( P < .01 ) . This favorable association was not evident in patients with astrocytoma or mixed oligoastrocytoma . CONCLUSION Combined loss of 1p and 19q is a statistically significant predictor of prolonged survival in patients with pure oligodendroglioma , independent of tumor grade . Given the lack of this association in patients with astrocytic neoplasms and the previously demonstrated chemosensitivity of oligodendrogliomas , a combined approach of histologic and genotypic assessment could potentially improve existing strategies for patient stratification and management Recent studies have shown that the clinical outcome of anaplastic oligodendroglial tumors is variable , but also that the histological diagnosis is subject to interobserver variation . We investigated whether the assessment of 1p/19q codeletion , polysomy of chromosome 7 , epidermal growth factor receptor ( EGFR ) gene amplification ( EGFR(amp ) ) , and loss of chromosome 10 or 10q offers additional prognostic information to the histological diagnosis and would allow molecular subtyping . For this study , we used the clinical data and tumor sample s of the patients included in multicenter prospect i ve phase III European Organisation for Research and Treatment of Cancer ( EORTC ) study 26951 on the effects of adjuvant procarbazine , chloroethyl cyclohexylnitrosourea ( lomustine ) , and vincristine chemotherapy in anaplastic oligodendroglial tumors . Fluorescence in situ hybridization was used to assess copy number aberrations of chromosome 1p , 19q , 7 , 10 , and 10q and EGFR . Three different analyses were performed : on all included patients based on local pathology diagnosis , on the patients with confirmed anaplastic oligodendroglial tumors on central pathology review , and on this latter group but after excluding anaplastic oligoastrocytoma ( AOA ) with necrosis . As a reference set for glioblastoma multiforme ( GBM ) , patients from the prospect i ve r and omized phase III study on GBM ( EORTC 26981 ) were used as a benchmark . In 257 of 368 patients , central pathology review confirmed the presence of an anaplastic oligodendroglial tumor . Tumors with combined 1p and 19q loss ( 1p(loss)19q(loss ) ) were histopathologically diagnosed as anaplastic oligodendroglioma , were more frequently located in the frontal lobe , and had a better outcome . Anaplastic oligodendroglial tumors with EGFR(amp ) were more frequently AOA , were more often localized outside the frontal lobe , and had a survival similar to that for GBM . Survival of patients with AOA harboring necrosis was in a similar range as for GBM , while patients with AOA with only endothelial proliferation had better overall survival . In univariate analyses , all molecular factors except loss of 10q were of prognostic significance , but on multivariate analysis a histopathological diagnosis of AOA , necrosis , and 1p(loss)19q(loss ) remained independent prognostic factors . AOA tumors with necrosis are to be considered WHO grade IV tumors ( GBM ) . Of all molecular markers analyzed in this study , especially loss of 1p/19q carried prognostic significance , while the others contributed little prognostic value to classical histology Although it has been demonstrated that the neuronal intermediate filament alpha‐internexin ( INA ) is closely related to 1p19q codeletion in gliomas , its prognostic and predictive value has not yet been confirmed in a prospect i ve trial . The authors of this report assessed the prognostic significance of INA expression and its correlation with relevant clinical and molecular characteristics in the prospect i ve , r and omized European Organization for Research and Treatment of Cancer ( EORTC ) 26951 trial of adjuvant procarbazine , lomustine , and vincristine ( PCV ) in patients with anaplastic oligodendroglial tumors ( AOTs ) Intergroup Radiation Therapy Oncology Group Trial 9402 study , a phase III trial of chemotherapy plus radiotherapy ( PCV‐plus‐RT ) vs. radiotherapy alone for pure and mixed anaplastic oligodendroglioma confirmed the prognostic significance of 1p 19q deletion and showed that only progression‐free survival ( PFS ) was prolonged in PCV‐plus‐RT‐treated patients and only in association with 1p 19q deletion . We review ed tumor histopathology , separating 115 tumors deemed to be classic for oligodendroglioma ( CFO ) from 132 lacking classic features of oligodendroglioma ( NCFO ) and evaluated the relationship of histopathology and 1p 19q status to treatment and outcome . The study disclosed : ( i ) overall survival ( OS ) of patients with CFO was significantly longer than for patients with NCFO ( P < 0.0001 ) and was not affected by necrosis . Median OS for CFO patients with and without necrosis was 6.6 and 6.3 years ( OS log‐rank P = not significant ) , respectively , in contrast to NCFO showing 1.9 and 3.3 years respectively ( OS log‐rank P = 0.014 ) . ( ii ) Classic oligodendroglial morphology was highly associated with 1p 19q deletion , present in 80 % of CFO and only in 13 % of NCFO . ( iii ) On multivariate analysis , both classic oligodendroglial morphology and 1p 19q deletion remained significantly associated with PFS and OS . ( iv ) Patients with CFO treated with PCV‐plus‐RT showed a trend toward increased survival compared with CFO treated with RT ( P = 0.08 ) . Median OS was not reached in the PCV‐plus‐RT group and was 6.3 years in RT group . These findings suggest that classic oligodendroglial morphology combined with 1p 19q deletion may in the future be predictive of chemotherapeutic response and survival PURPOSE Anaplastic oligodendrogliomas are more responsive to chemotherapy than high- grade astrocytomas . We investigated , in a multicenter r and omized controlled trial , whether adjuvant procarbazine , lomustine , and vincristine ( PCV ) chemotherapy improves overall survival ( OS ) in newly diagnosed patients with anaplastic oligodendrogliomas or anaplastic oligoastrocytomas . PATIENTS AND METHODS The primary end point of the study was OS ; secondary end points were progression-free survival ( PFS ) and toxicity . Patients were r and omly assigned to either 59.4 Gy of radiotherapy ( RT ) in 33 fractions only or to the same RT followed by six cycles of st and ard PCV chemotherapy ( RT/PCV ) . 1p and 19q deletions were assessed with fluorescent in situ hybridization . RESULTS A total of 368 patients were included . The median follow-up time was 60 months , and 59 % of patients have died . In the RT arm , 82 % of patients with tumor progression received chemotherapy . In 38 % of patients in the RT/PCV arm , adjuvant PCV was discontinued for toxicity . OS time after RT/PCV was 40.3 months compared with 30.6 months after RT only ( P = .23 ) . RT/PCV increased PFS time compared with RT only ( 23 v 13.2 months , respectively ; P = .0018 ) . Twenty-five percent of patients were diagnosed with combined 1p/19q loss ; 74 % of this subgroup was still alive after 60 months . RT/PCV did not improve survival in the subgroup of patients with 1p/19q loss . CONCLUSION Adjuvant PCV chemotherapy does not prolong OS but does increase PFS in anaplastic oligodendroglioma . Combined loss of 1p/19q identifies a favorable subgroup of oligodendroglial tumors . No genetic subgroup could be identified that benefited with respect to OS from adjuvant PCV PURPOSE Anaplastic oligodendroglioma ( AO ) and anaplastic oligoastrocytoma ( AOA ) are treated with surgery and radiotherapy ( RT ) at diagnosis , but they also respond to procarbazine , lomustine , and vincristine ( PCV ) , raising the possibility that early chemotherapy will improve survival . Furthermore , better outcomes in AO have been associated with 1p and 19q allelic loss . PATIENTS AND METHODS Patients with AO and AOA were r and omly assigned to PCV chemotherapy followed by RT versus postoperative RT alone . The primary end point was overall survival . The status of 1p and 19q alleles was assessed by fluorescence in situ hybridization . RESULTS Two hundred eighty-nine eligible patients were r and omly assigned to either PCV plus RT ( n = 147 ) or RT alone ( n = 142 ) . At progression , 80 % of patients r and omly assigned to RT had chemotherapy . With 3-year follow-up on most patients , the median survival times were similar ( 4.9 years after PCV plus RT v 4.7 years after RT alone ; hazard ratio [ HR ] = 0.90 ; 95 % CI , 0.66 to 1.24 ; P = .26 ) . Progression-free survival time favored PCV plus RT ( 2.6 years v 1.7 years for RT alone ; HR = 0.69 ; 95 % CI , 0.52 to 0.91 ; P = .004 ) , but 65 % of patients experienced grade 3 or 4 toxicity , and one patient died . Patients with tumors lacking 1p and 19q ( 46 % ) compared with tumors not lacking 1p and 19q had longer median survival times ( > 7 v 2.8 years , respectively ; P < or = .001 ) ; longer progression-free survival was most apparent in this subset . CONCLUSION For patients with AO and AOA , PCV plus RT does not prolong survival . Longer progression-free survival after PCV plus RT is associated with significant toxicity . Tumors lacking 1p and 19q alleles are less aggressive or more responsive or both Treatment for newly diagnosed anaplastic oligodendroglial tumors is controversial . Radiotherapy ( RT ) alone and in combination with chemotherapy ( CT ) are the most well studied strategies . However , CT alone is often advocated , especially in cases with 1p19q codeletion . We retrospectively identified 1013 adults diagnosed from 1981 - 2007 treated initially with RT alone ( n = 200 ) , CT + RT ( n = 528 ) , CT alone ( n = 201 ) , or other strategies ( n = 84 ) . Median overall survival ( OS ) was 6.3 years and time to progression ( TTP ) was 3.1 years . 1p19q codeletion correlated with longer OS and TTP than no 1p or 19q deletion . In codeleted cases , median TTP was longer following CT + RT ( 7.2 y ) than following CT ( 3.9 y , P = .003 ) or RT ( 2.5 y , P < .001 ) alone but without improved OS ; median TTP was longer following treatment with PCV alone than temozolomide alone ( 7.6 vs. 3.3 y , P = .019 ) . In cases with no deletion , median TTP was longer following CT + RT ( 3.1 y ) than CT ( 0.9 y , P = .0124 ) or RT ( 1.1 y , P < .0001 ) alone ; OS also favored CT + RT ( median 5.0 y ) over CT ( 2.2 y , P = .02 ) or RT ( 1.9 y , P < .0001 ) alone . In codeleted cases , CT alone did not appear to shorten OS in comparison with CT + RT , and PCV appeared to offer longer disease control than temozolomide but without a clear survival advantage . Combined CT + RT led to longer disease control and survival than did CT or RT alone in cases with no 1p19q deletion . Ongoing trials will address these issues prospect ively PURPOSE To examine the rate and duration of response of anaplastic oligodendrogliomas to a dose-escalated combination chemotherapy regimen consisting of procarbazine , lomustine ( CCNU ) , and vincristine ( PCV ) and to evaluate the side effects of this treatment . METHODS In this single-arm multicentered phase II study , patients with measurable , newly diagnosed or recurrent , contrast-enhancing anaplastic oligodendrogliomas were treated with up to six cycles of PCV . Central pathology and radiology review were m and atory , and rigorous response criteria based on imaging were used . RESULTS Thirty-three patients entered the trial ; nine were excluded subsequently , seven due to ineligible pathology . Eighteen of 24 eligible patients ( 75 % ) responded , nine completely ( 38 % ) , four had stable disease ( SD ) , and two progressed during the first cycle of PCV . Responses were observed in nine of 10 patients ( 90 % ) with a preexisting low- grade oligodendroglioma and 10 of 15 ( 67 % ) with necrotic tumors , called glioblastoma multiforme by some . Previously irradiated patients were as likely to respond to PCV as those newly diagnosed ( 11 of 15 [ 73 % ] v seven of nine [ 78 % ] ) . The median time to progression will be at least 25.2 months for complete responders , and was 14.2 months for partial responders and 6.8 months for stable patients . Four ineligible patients also responded to PCV ; all had gliomas with oligodendroglial differentiation . All responders , eligible or ineligible , were stable or improved neurologically , but nine of 22 ( 41 % ) experienced a decline in Eastern Cooperative Oncology Group ( ECOG ) performance status of one grade while on PCV . Adverse events on treatment included a death from Pneumocystis pneumonia , a severe reversible encephalopathy due to procarbazine , an intratumoral hemorrhage , and a subdural hematoma . All other acute toxicities were anticipated and manageable . CONCLUSION Anaplastic oligodendrogliomas are chemosensitive brain cancers . Patients with these tumors respond predictably , durably , and often completely to PCV , and many tolerate a dose-escalated formulation . Cooperative group and r and omized trials will be necessary to explore fully the role of chemotherapy in the treatment of aggressive oligodendrogliomas BACKGROUND Glioblastoma , the most common primary brain tumor in adults , is usually rapidly fatal . The current st and ard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible , followed by adjuvant radiotherapy . In this trial we compared radiotherapy alone with radiotherapy plus temozolomide , given concomitantly with and after radiotherapy , in terms of efficacy and safety . METHODS Patients with newly diagnosed , histologically confirmed glioblastoma were r and omly assigned to receive radiotherapy alone ( fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks , for a total of 60 Gy ) or radiotherapy plus continuous daily temozolomide ( 75 mg per square meter of body-surface area per day , 7 days per week from the first to the last day of radiotherapy ) , followed by six cycles of adjuvant temozolomide ( 150 to 200 mg per square meter for 5 days during each 28-day cycle ) . The primary end point was overall survival . RESULTS A total of 573 patients from 85 centers underwent r and omization . The median age was 56 years , and 84 percent of patients had undergone debulking surgery . At a median follow-up of 28 months , the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone . The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 ( 95 percent confidence interval , 0.52 to 0.75 ; P<0.001 by the log-rank test ) . The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone . Concomitant treatment with radiotherapy plus temozolomide result ed in grade 3 or 4 hematologic toxic effects in 7 percent of patients . CONCLUSIONS The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma result ed in a clinical ly meaningful and statistically significant survival benefit with minimal additional toxicity PURPOSE Anaplastic oligodendrogliomas , pure ( AO ) and mixed ( anaplastic oligoastrocytoma [ AOA ] ) , are chemosensitive , especially if codeleted for 1p/19q , but whether patients live longer after chemoradiotherapy is unknown . PATIENTS AND METHODS Eligible patients with AO/AOA were r and omly assigned to procarbazine , lomustine , and vincristine ( PCV ) plus radiotherapy ( RT ) versus RT alone . The primary end point was overall survival ( OS ) . RESULTS Two hundred ninety-one eligible patients were r and omly assigned : 148 to PCV plus RT and 143 to RT . For the entire cohort , there was no difference in median survival by treatment ( 4.6 years for PCV plus RT v 4.7 years for RT ; hazard ratio [ HR ] = 0.79 ; 95 % CI , 0.60 to 1.04 ; P = .1 ) . Patients with codeleted tumors lived longer than those with noncodeleted tumors ( PCV plus RT : 14.7 v 2.6 years , HR = 0.36 , 95 % CI , 0.23 to 0.57 , P < .001 ; RT : 7.3 v 2.7 years , HR = 0.40 , 95 % CI , 0.27 to 0.60 , P < .001 ) , and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT ( 14.7 v 7.3 years ; HR = 0.59 ; 95 % CI , 0.37 to 0.95 ; P = .03 ) . For those with noncodeleted tumors , there was no difference in median survival by treatment arm ( 2.6 v 2.7 years ; HR = 0.85 ; 95 % CI , 0.58 to 1.23 ; P = .39 ) . In Cox models that included codeletion status , the adjusted OS for all patients was prolonged by PCV plus RT ( HR = 0.67 ; 95 % CI , 0.50 to 0.91 ; P = .01 ) . CONCLUSION For the subset of patients with 1p/19q codeleted AO/AOA , PCV plus RT may be an especially effective treatment , although this observation was derived from an unplanned analysis |
12,480 | 18,050,149 | The results indicate that an audiotape of the patients ' own consultation has added value upon oral information only .
However , providing patients with a general audiotape does not improve recall of information and might even inhibit patients ' recall .
Furthermore , there is scientific evidence , although limited , that the use of a question prompt sheet ( QPS ) has a positive effect on recall of information , provided that the physician actively endorses this sheet .
No evidence was found for an effect of providing patients with a summary letter of the consultation on recall , although research on this subject is scarce .
In conclusion , the review suggests that interventions that are tailored to the individual cancer patient , such as an audiotape of the consultation or a QPS , are most effective . | This systematic review investigates which interventions are effective to improve recall of medical information in cancer patients . | PURPOSE By means of a r and omized double-blind study , the effect of providing taped initial consultations on cancer patients ' satisfaction , recall , and quality of life was investigated . PATIENTS AND METHODS Consecutive cancer patients referred to either the gynecology or medical oncology outpatient clinic were eligible . Initial consultations were audiotaped . Patients were either provided with the tape ( experimental group ) or not ( control group ) . Baseline variables included sociodemographics , preferences for information , coping styles , and clinical characteristics . Follow-up ( after 1 week and 3 months ) variables included attitudes toward the intervention , satisfaction , recall , and quality of life . Assessment s took place through mailed question naires and telephone interviews . RESULTS Two hundred one patients were included ( response , 71 % ) , 105 in the experimental group and 96 in the control group . Most patients ( 75 % ) listened to the tape , the majority of which ( 73 % ) listened with others . Almost all patients , both in the experimental group ( 96 % ) and control group ( 98 % ) were positive about the intervention . Expectations were confirmed ; patients provided with the tape were more satisfied ( P < .05 ) and recalled more information ( P < .01 ) than patients without the tape . The intervention did not have an effect on quality of life . An interaction effect was found between the intervention and patients ' age on satisfaction with the taped consultation ( P < .01 ) and recall of diagnostic information ( P < .01 ) ; access to tapes seems more helpful in enhancing satisfaction in younger patients and recall of diagnostic information in older patients . CONCLUSION Cancer patients and their families value the taped initial consultation . This intervention enhances their satisfaction and improves their recall of information . Tapes seem more helpful in enhancing satisfaction in younger patients and recall of diagnostic information in older patients OBJECTIVES To evaluate the impact of an information booklet on HIV clinical trials , Clinical Trials in HIV and AIDS : Information For People Who Are Thinking About Joining a Trial , in addition to the st and ard trial information ( SI ) on patients ' knowledge ; underst and ing and attitudes about clinical trials ; and to investigate patients ' motivations and reasons for enrolling or not enrolling in a clinical trial . METHODS Fifty HIV-1 positive patients who attended the HIV clinic at a west London hospital were r and omized to receive either SI alone ( n = 27 ) or SI and a 16 page information booklet explaining the principles and procedures of HIV clinical trials ( n = 23 ) . A self-administered question naire was used at baseline to assess past experience and attitudes to clinical trials ( 10 questions ) , knowledge and underst and ing of HIV treatments ( 8 questions ) and clinical trials ( 11 questions ) . At 2 - 6 months after r and omization , a second interviewer-administered question naire addressed the patient 's assessment of the usefulness and comprehensiveness of the information provided by the SI and information booklet , whether or not the patient had enrolled in a clinical trial and reasons for enrolling/not enrolling , knowledge of specific aspects of the trial protocol the patient was eligible to join ( 13 questions ) and general knowledge of clinical trial procedures ( repeat of 11 baseline questions ) . Changes in the attitudes and scores on knowledge and underst and ing of clinical trials were compared for the two groups . RESULTS In both groups , patient knowledge of clinical trial procedures improved significantly over the study period . The median score increased from 30 at baseline to 35/44 at follow-up ( SI only ) vs. 24 - 31/44 ( SI plus booklet ) , but this did not differ significantly between the two groups . However , knowledge of the specific trial protocol was poor [ median score 13/25 , interquartile range ( IQR ) 8 - 14 ] , and there was no difference in the scores for the two groups . The prime motivations for joining a clinical trial were to benefit personal health and to gain access to new treatments . Potential side-effects were the main concern of prospect i ve trial participants . CONCLUSIONS This small trial shows that , while the patients ' general knowledge and underst and ing of clinical trials improved over time , this was not improved by the information booklet and re collection of the details of the relevant trial protocol remained poor Active participation in the medical consultation has been demonstrated to benefit aspects of patients ’ subsequent psychological well-being . We investigated two interventions promoting patient question -asking behaviour . The first was a question prompt sheet provided before the consultation , which was endorsed and worked through by the clinician . The second was a face to face coaching session exploring the benefits of , and barriers to , question -asking , followed by coaching in question -asking behaviour employing rehearsal techniques . Sixty patients with heterogeneous cancers , seeing two medical oncologists for the first time , were r and omly assigned to one of three groups : two intervention groups and one control group . Sociodemographic variables and anxiety were assessed prior to the intervention which preceded the consultation . The consultations were audiotaped and subsequently analysed for question -asking behaviour . Anxiety was assessed again immediately following the consultation . Question naires to assess patient satisfaction , anxiety and psychological adjustment were sent by mail 2 weeks following the consultation . Presentation and discussion of the prompt sheet significantly increased the total number of questions asked and the number of questions asked regarding tests and treatment . Coaching did not add significantly to the effects of the prompt sheet . Psychological outcomes were not different among the groups . We conclude that a question prompt sheet addressed by the doctor is a simple , inexpensive and effective means of promoting patient question asking in the cancer consultation Patient participation in medical consultations has been demonstrated to benefit their subsequent psychological well being . Question asking is one way in which patients can be active . We investigated 2 means of promoting cancer patient question asking . One was the provision of a question prompt sheet to patients prior to their initial consultation with their oncologist . The second was the active endorsement and systematic review of the question prompt sheet by their oncologist . 318 patients with heterogeneous cancers , seeing one of 5 medical and 4 radiation oncologists for the first time , were r and omised to either receive or not receive a question prompt sheet . Doctors were r and omised to either proactively address or passively respond to the question prompt sheet in the subsequent consultation . Anxiety was assessed prior to the consultation . Consultations were audiotaped and content analysed . Anxiety was assessed again immediately following the consultation . Within the next 10 days patients completed question naires assessing information needs , anxiety and satisfaction and were given a structured telephone interview assessing information recall . Patients provided with a question prompt sheet asked more questions about prognosis compared with controls and oncologists gave significantly more prognostic information to these patients . Provision of the question prompt sheet prolonged consultations and increased patient anxiety ; however , when oncologists specifically addressed the prompt sheet , anxiety levels were significantly reduced , consultation duration was decreased and recall was significantly improved . A patient question prompt sheet , used proactively by the doctor , is a powerful addition to the oncology consultation . © 2001 Cancer Research Campaign PURPOSE Women with breast cancer were provided with an audiotape of their primary adjuvant treatment consultation , and the following patient outcomes were measured at 12 weeks postconsultation : perceived degree of information provision , audiotape satisfaction and use , communication satisfaction with oncologist , mood state , and cancer-specific quality of life . PATIENTS AND METHODS Participants included 628 women newly diagnosed with breast cancer and 40 oncologists from six cancer centers in Canada . The patients were block r and omized to one of four consultation groups : st and ard care control , not audiotaped ; audiotaped , no audiotape given ; audiotaped , patient given audiotape ; and audiotaped , patient offered choice of receiving audiotape or not . RESULTS Patients receiving the consultation audiotape had significantly better recall of having discussed side effects of treatment than patients who did not receive the audiotape . Audiotape benefit was not significantly related to patient satisfaction with communication , mood state , or quality of life at 12 weeks postconsultation , and was not significantly affected by choice of receiving the audiotape . Patients rated the audiotape intervention positively , with an average score of 83.9 of 100 . CONCLUSION Audiotape provision benefits patients by facilitating their perception of being informed about treatment side effects , but does not significantly influence patient satisfaction with communication , mood state , or quality of life PURPOSE Studies of tape recordings of cancer consultations have produced conflicting results . At the same time , audiotapes containing general information about cancer are poorly evaluated and are distributed to patients in an ad hoc manner . We compared the effects of both interventions on patient satisfaction , psychologic adjustment , and recall of information following their first consultation with a medical oncologist . PATIENTS AND METHODS Patients ( n = 142 ) were r and omized to receive ( 1 ) an audiotape of their consultation , ( 2 ) an audiotape describing cancer in general terms , or ( 3 ) no tape . Recall of information was assessed in a structured interview 4 to 20 days after the consultation . RESULTS Satisfaction with the consultation increased linearly from no tape to general tape to consultation tape . Satisfaction with the tape itself was higher in patients who received the consultation tape ( satisfaction score , 61 % ) compared with those who received the general tape ( 43 % ) . Average recall for all groups was 6.4 of the 25 items of information presented , and 2.4 of the six points identified as particularly important by the oncologist . The consultation tape did not improve recall over the no tape control , but the general tape caused a decrease of almost two items in total recall . Spontaneous ( ie , unprompted ) recall was significantly poorer with the general information tape . Psychologic adjustment to cancer was unaffected . CONCLUSION We conclude that individual audiotapes have a limited potential to increase recall of information from the oncology consultation . General information tapes about cancer appear to inhibit recall actively Abstract OBJECTIVE : To assess the effect of video and pamphlet interventions on patient prostate cancer ( CaP ) screening knowledge , decision-making participation , preferences , and behaviors . DESIGN : R and omized , controlled trial . SETTING : Four midwestern Veterans Affairs medical facilities . PATIENTS / PARTICIPANTS : One thous and , one hundred fifty-two male veterans age 50 and older with primary care appointments at participating facilities were r and omized and 893 completed follow-up . INTERVENTIONS : Patients were r and omized to mailed pamphlet , mailed video , or usual care/control . MEASUREMENTS AND MAIN RESULTS : Outcomes assessed by phone survey 2 weeks postintervention included a 10-item knowledge index ; correct responses to questions on CaP natural history , treatment efficacy , the prostate-specific antigen ( PSA ) ’s predictive value , and expert disagreement about the PSA ; whether screening was discussed with provider ; screening preferences ; and PSA testing rates . Mean knowledge index scores were higher for video ( 7.44 ; P=.001 ) and pamphlet ( 7.26 ; P=.03 ) subjects versus controls ( 6.90 ) . Video and pamphlet subjects reported significantly higher percentages of correct responses relative to controls to questions on CaP natural history ( 63 % , 63 % , and 54 % , respectively ) ; treatment efficacy ( 19 % , 20 % , and 5 % ) , and expert disagreement ( 28 % , 19 % , and 8 % ) , but not PSA accuracy ( 28 % , 22 % , and 22 % ) . Pamphlet subjects were more likely than controls to discuss screening with their provider ( 41 % vs 32 % ; P=.03 ) but video subjects were not ( 35 % ; P=.33 ) . Video and pamphlet subjects were less likely to intend to have a PSA , relative to controls ( 63 % , 65 % , and 74 % , respectively ) . PSA testing rates did not differ significantly across groups . CONCLUSIONS : Mailed interventions enhance patient knowledge and self-reported participation in decision making , and alter screening preferences . The pamphlet and video interventions evaluated are comparable in effectiveness . The lower-cost pamphlet approach is an attractive option for clinics with limited re sources Open or uncontrolled studies have suggested that providing cancer patients with audiotapes of their clinical interviews can improve information recall and reduce psychological distress . We tested these hypotheses in a ' clinician-blind ' , prospect i ve , r and omised controlled trial . A total of 117 patients newly referred to a medical oncology clinic who were to be given ' bad news ' had their consultations audiotaped . Blind to the clinician , patients were r and omly allocated to receive a copy of the tape to play at home or not ( control group ) . At 6 months follow-up , tape group patients reported positive attitudes to the audiotape and were shown to recall significantly more information about their illness than did controls . Overall improvement in psychological distress at 1 and 6 months follow-up , as measured with the 30-item General Health Question naire and the Hospital Anxiety and Depression Scale was no different in the two groups . However , a second-order interaction suggested that poor-prognosis patients were disadvantaged specifically by access to the audiotape , with less improvement in psychological distress at 6 months follow-up than non-tape controls . Patient access to audiotapes of clinical interviews promotes factual retention but does not reliably reduce psychological distress and may be actively unhelpful in some subgroups of patients Summary A range of measures have been proposed to enhance the provision of information to cancer patients and r and omized controlled trials have demonstrated their impact on patient satisfaction and recall . The current study explored the practice and views of oncologists , surgeons and general practitioners ( GPs ) with regards to providing patients with consultation audiotapes and summary letters . In stage 1 , 28 semi-structured interviews with doctors were conducted to provide qualitative data on which to base a question naire . In stage 2 , 113 medical oncologists , 43 radiation oncologists , 55 surgeons and 108 GPs completed question naires . Only one-third of doctors had ever provided patients with a copy of the letter written to the oncologist or referring doctor , and one-quarter had provided a summary letter or tape . The majority of doctors were opposed to such measures ; however , a substantial minority were in favour of providing a letter or tape under certain conditions . More surgeons and GPs ( > two-thirds ) were opposed to specialists providing a consultation audiotape than oncologists ( one-third ) . Gender , years of experience and attitude to patient involvement in decision-making were predictive of doctors ’ attitudes . The majority of doctors remain opposed to offering patients personalized information aids . However , practice and perspectives appear to be changing A question prompt list ( QPL ) is a structured list of questions design ed to encourage patients to acquire information during a medical consultation . It has been shown to be an effective , inexpensive means of helping cancer patients ask questions in certain content areas when consulting an oncologist . The objective of this study was to develop a QPL for cancer patients seeing a surgeon initially , targeting issues identified by patients as important . Focus groups and structured interviews were convened with 22 cancer patients . One focus group was conducted with allied health professionals . Focus groups were audiotaped , transcribed and content analysed to ensure all issues were identified . The results led to the identification of 59 questions covering five themes . We have grouped the questions under the following themes : preliminary negotiation and discussion of diagnosis and its implication s ; further investigations — why and how ; am I seeing the right doctor — who else should I see ? ; treatment information and options ; and support . Participants believed that the QPL would be useful not only during diagnosis and discussion s regarding the surgical care but also subsequently . Patients felt that provision and endorsement of a QPL would assist them to achieve their information needs and participation preferences The purpose of this study was to determine the helpfulness of a prompt sheet versus a general information sheet for patient communication with physicians . Sixty women with breast cancer attending their first outpatient consultation with a breast medical oncologist were r and omized to receive either a prompt sheet ( PS ) or a general information ( GI ) sheet regarding breast cancer . Analysis of the results found that helpfulness of the written material was rated higher in the PS group ( 8.5 + /- 2 ) than the GI group ( 6.2 + /- 3.6 ) , P = 0.005 . The mean score of helpfulness in communicating with physicians was 7.9 + /- 2.4 and 5.7 + /- 3.8 , respectively , P = 0.01 . There were no significant differences between the groups in the average total number of questions asked by the patients or average physician or patient speaking time . We conclude that a disease-specific prompt sheet provided before medical encounters may assist in communication between patients and physicians To determine whether st and ardized instructions enhance communication of discharge information , we provided 197 parents of children in whom otitis media was diagnosed with one of three types of instruction at the time of discharge from a pediatric emergency department : ( 1 ) instruction by individual housestaff and medical students after consultation with an attending physician ( control group ) ; ( 2 ) st and ardized verbal instructions given by housestaff and students trained in their use ( verbal group ) ; or ( 3 ) the same instructions given to the verbal group , together with a type-written copy of the information to take home ( verbal + written group ) . Prior to leaving the emergency department and , again , by phone , 1 and 3 days later , parents were question ed concerning the prescribed medication 's name , dose , frequency , and duration of administration ( medication data ) , three signs of improvement , and eight signs indicating the need for medical advice ( worrisome signs ) . The mean percentage of correct responses per parent in each group was computed for each information category . Both at exit interview and at follow-up , parents receiving either form of st and ardized instructions showed significantly greater knowledge of information related to their child 's illness than did controls . Information regarding medication data was more likely to be communicated to parents in all groups than were signs of improvement or worrisome signs . The addition of written instructions to st and ardized verbal instructions did not improve parental recall of discharge information OBJECTIVE To vali date the usefulness of written information for patients with venous leg ulcers and test the hypothesis that patients who receive written information retain more knowledge than those who receive verbal information alone . METHOD Twenty patients newly diagnosed with venous leg ulcers were recruited into this prospect i ve trial . Patients were r and omised either to the control group ( given verbal information on their condition ) or the intervention group ( same verbal information and an information leaflet ) . The verbal information was in the same format as in the leaflet . Patients ' knowledge of the condition was ascertained at an initial interview and at follow-up four to six weeks later . RESULTS At follow-up both groups showed an overall improvement in knowledge , with no statistical difference between them . CONCLUSION The results indicate there is limited value in providing information leaflets to this patient group , who were predominantly older patients with low levels of education . The relatively small sample size may explain the disappointing results . Further research may reveal a benefit of providing these leaflets to carers An important goal in oncology nursing is to provide out patients receiving chemotherapy with adequate information about their treatment so they will be able to cope with treatment reactions and make appropriate decisions about seeking early medical attention when potentially serious side-effects occur . The purpose of the present study was to evaluate patient teaching strategies at one cancer centre . A comparative descriptive study design was employed . A group of patients receiving one-to-one nurse/patient teaching was compared to a group of patients receiving one-to-one nurse/patient teaching plus a take-home instructional chemotherapy video . The patient groups were compared with respect to : a ) level of recall of chemotherapy information ; b ) the sources of information used ; and c ) preferred information sources . When the mean scores achieved on the chemotherapy knowledge question naire were compared , no statistically significant differences were found between the two groups . In fact , both groups showed a " high " level of information recall . Both patient groups reported using a variety of information sources to learn about their chemotherapy , however , for both groups the preferred sources of information were their direct health care providers . The results of the study raise interesting issues about the feasibility of developing " high-tech " patient education strategies BACKGROUND The purpose of this study was to systematic ally compare two audiotape formats for the delivery of information relevant to informed consent to participate in a clinical trial in breast oncology , and to establish the feasibility of adding a consultation recording protocol to a clinical treatment trial . METHOD Participants were 69 women with newly diagnosed breast cancer and 21 oncologists from 5 Canadian cancer centers . Patients were block r and omized to one of three groups : 1 . st and ardized audiotape ; 2 . consultation audiotape ; or 3 . both audiotapes . Patients received their tapes immediately following the clinical trial consultation . Patient outcomes included perception of being informed about clinical trials , knowledge of information relevant to providing informed consent to a clinical trial , and satisfaction with communication during the consultation . RESULTS The consultation audiotapes contained less trial-related information than the st and ardized audiotape but there were no differences in clinical trial knowledge or perception of being informed across the intervention groups . Patients expressed a marginally significant preference for consultation audiotapes over st and ardized audiotapes . CONCLUSIONS Patients tended to prefer receiving an audiotape of their own consultation over a st and ardized audiotape . The majority of oncologists considered the audiotape intervention feasible but were less enthusiastic about being involved in a larger study given the accrual challenges that arose when trying to " piggy-back " one r and omized controlled trial on an existing clinical trial Communication between physicians and advanced cancer patients is frequently difficult . Patients often report poor levels of satisfaction with communication . The purpose of this study was to assess the impact on patients ' recall of and overall satisfaction with their consultation by the addition of an audiocassette recording of a consultation to written recommendations OBJECTIVE --To determine whether a booklet given to patients being discharged from hospital giving details of their admission and treatment increased their knowledge and recall when review ed in outpatient clinics . DESIGN -- Patients alternately allocated to receive a booklet or to serve as controls . Assessment by a question naire at first attendance at outpatient clinic after discharge . Data were collected over nine months . SETTING --One general medical and cardiological ward in a large teaching hospital and associated outpatient clinics . PATIENTS --One hundred and thirty one patients discharged taking at least one drug and scheduled to return to clinic within 12 weeks . Patients stratified by age and by the number of weeks between discharge and outpatient appointment . INTERVENTION -- A booklet was given to 65 patients at discharge from the ward ; 66 patients served as controls . MAIN RESULTS --Of the patients who received the booklet , 56 ( 86 % ) knew the names of their drugs , 62 ( 95 % ) the frequency of the dose , and 55 ( 85 % ) the reasons for taking each drug . The numbers in the control group were 31 ( 47 % ) , 38 ( 58 % ) , and 28 ( 42 % ) respectively . These differences were highly significant ( p less than 0.001 ) . Twenty six ( 40 % ) who received the booklet brought all their drugs to clinic compared with 12 ( 18 % ) control patients . Appreciably more of the first group of patients than control patients knew the reason they had been in hospital , and more of the first group indicated that they would take the correct action when their prescribed drugs ran out . Most general practitioners thought that the booklet was a good idea , that it was helpful , and that it was better than the existing interim discharge letter . CONCLUSIONS --Giving patients an information booklet at discharge from hospital appreciably increased the accuracy and thoroughness of their recall of important medical details concerning their illness and its treatment . The booklet was shown to be feasible , helpful in the outpatient clinic , and preferred by most general practitioners BACKGROUND The purpose of this investigation was to systematic ally examine the efficacy of providing men with prostate cancer with an audiotape of their primary treatment consultation . METHOD Participants included 425 men newly diagnosed with prostate cancer and 15 radiation oncologists from 4 cancer centers in Canada . Patients were block r and omized to one of four consultation groups : 1 . St and ard care control -- not audio-taped ; 2 . Audio-taped -- no audiotape given ; 3 . Audio-taped -- patient given audiotape ; and 4 . Audio-taped -- patient offered choice of receiving audiotape or not ( 4 patients declined ; 94 accepted ) . Patient outcomes were measured at 12 weeks post-consultation : perceived degree of information provision ; audiotape satisfaction and use ; communication satisfaction with oncologist ; mood state ; and cancer-specific quality of life . RESULTS Patients receiving the consultation audiotape reported having been provided with significantly more disease and treatment information in general ( p=0.04 ) , and more information about treatment alternatives ( p=0.04 ) and treatment side effects ( p=0.01 ) in particular , than patients who did not receive the audiotape . Audiotape benefit was not significantly related to patient satisfaction with communication , mood state or quality of life at 12 weeks post-consultation , and was not significantly affected by choice of receiving the audiotape . Patients rated the audiotape intervention positively , with an average score of 83.0 out of 100 . CONCLUSION Consultation audiotapes are rated highly by men with prostate cancer , and these audiotapes help to enhance their perception of having been provided with critical disease- and treatment-related information Study Design . R and omized controlled factorial trial . Objective . To assess the effectiveness of a booklet and of physician advice to take regular exercise . Summary of Background Data . Educational booklets are one of the simplest interventions for back pain but have not been shown to alter pain and function . Although there is evidence that advice to mobilize is effective , doctors have also been advised to encourage regular exercise — but there is no evidence that such advice alone improves outcomes . Method . Eight doctors from six practice s r and omized 311 patients with a new episode of back pain using sealed numbered opaque envelopes to receive a detailed self-management booklet , advice to take regular exercise , both , or neither . All groups were advised to mobilize and to use simple analgesia . Patients were telephoned during the first week after entry into the study , and after 3 weeks to assess a vali date d numerical pain/function score ( 0 = no pain normal activities to 100 = extreme pain no normal activities ) . Patients also returned a postal question naire in the first week with the Aberdeen pain and function scale , a knowledge score , and a reliable satisfaction scale ( mean score of 4 items : 0 = not satisfied to 100 = extremely satisfied ) . Results . Pain/function scores were obtained in 239 ( 77 % ) patients . There were interactions between exercise and booklet groups for both pain/function scores and the Aberdeen scale , which are unlikely to have been chance findings ( P = 0.009 and P = 0.012 , respectively ) . In comparison with the control group , there were reductions in the pain/function score in the first week with a booklet ( −8.7 , 95 % CI −17.4 to −0.03 ) or advice to exercise ( −7.9 ; −16.7 to 0.8 ) but much less effect with both together ( −0.08 , −9.0 to 8.9 ) . Similarly , the Aberdeen scale was lower in the booklet group ( −3.8 , −7.7 to 0.07 ) and in the exercise advice group ( −5.3 ; −9.3 to −1.38 ) but much less with both combined ( −1.9 , −5.8 to 2.1 ) . There was no significant difference between groups in pain/function scores by week 3 , when 58 % reported being back to normal . Satisfaction was increased in booklet ( 7.9 , 1.3 to 14.4 ) and exercise groups ( 7.4 , 0.8 to 13.9 ) ) , and a booklet also increased knowledge ( Kruskal-Wallis & khgr;2 27.2 , P = 0.001 ) . Conclusion . Doctors can increase satisfaction and moderately improve functional outcomes in the period immediately after the consultation when back pain is worst , by using very simple interventions : either by endorsing a self-management booklet or by giving advice to take exercise . Previous studies suggest that simple advice and the same written information provide reinforcement . This study supports evidence that it may not be helpful to provide a detailed information booklet and advice together , where the amounts or formats of information differ BACKGROUND Active participation and asking questions are important ways in which patients can ensure they underst and what the doctor has said . This study evaluated a question prompt sheet design ed to encourage patients to ask questions in the cancer consultation . PATIENTS AND METHODS Patients ( n = 142 ) were r and omised to receive ( i ) a question prompt sheet or ( ii ) a general sheet informing patients of services available through the regional Cancer Council . Recall of information was assessed in a structured interview 4 - 20 days after the consultation . Question naires to assess patient satisfaction and adjustment to cancer were sent by mail . RESULTS The question prompt sheet had a significant effect in one content area : prognosis . Thirty-five percent of patients who received the question h and out asked questions about prognosis compared to 16 % of those receiving the information h and out . The prompt sheet did not increase the mean number of questions asked overall . Age , in/out-patient status , gender and involvement preference were predictive of both number and duration of patient questions . CONCLUSIONS A question prompt sheet has a limited but important effect on patient question asking behaviour in the cancer consultation This paper describes a pilot study of information giving in an oncology setting . This was achieved by r and omly allocating patients to having their consultation tape-recorded or not . The results suggest that this approach increases the retention of information in patients as well as reducing their levels of anxiety . The method is cheap and easy to use , acceptable to patients and their families , and does not inhibit the consultation process PURPOSE This study evaluated a cancer consultation preparation package ( CCPP ) design ed to facilitate patient involvement in the oncology consultation . PATIENTS AND METHODS A total of 164 cancer patients ( 67 % response rate ) were r and omly assigned to receive the CCPP or a control booklet at least 48 hours before their first oncology appointment . The CCPP included a question prompt sheet , booklets on clinical decision making and patient rights , and an introduction to the clinic . The control booklet contained only the introduction to the clinic . Physicians were blinded to which intervention patients received . Patients completed question naires immediately after the consultation and 1 month later . Consultations were audiotaped , transcribed verbatim , and coded . RESULTS All but one patient read the information . Before the consultation , intervention patients were significantly more anxious than were controls ( mean , 42 v 38 ; P = .04 ) ; however anxiety was equivalent at follow-up . The CCPP was reported as being significantly more useful to family members than the control booklet ( P = .004 ) . Patients receiving the intervention asked significantly more questions ( 11 v seven questions ; P = .005 ) , tended to interrupt the physician more ( 1.01 v 0.71 interruptions ; P = .08 ) , and challenged information significantly more often ( twice v once ; P = .05 ) . Patients receiving the CCPP were less likely to achieve their preferred decision making style ( 22 % ) than were controls ( 35 % ; P = .06 ) . CONCLUSION This CCPP influences patients ' consultation behavior and does not increase anxiety in the long-term . However , this intervention , without physician endorsement , reduced the percentage of patients whose preferred involvement in decision making was achieved Numerous studies have shown that patients are usually dissatisfied with the information they receive during clinical consultations with medical specialists . Therefore , a r and omised study design has been used to assess the role of personal letters to patients outlining their cancer consultation . Compared with the control group , patients receiving letters were more satisfied with the amount of information given , and tended to have greater and more accurate recall of the consultation . A survey of referring doctors revealed general support for the idea of sending to cancer patients letters that outline the substance of their consultations . The study shows that letters to patients are a useful method of improving patient satisfaction and recall in clinical consultations . They also provide a permanent record of the consultation , which can be kept for future reference , and encourage greater patient involvement in their care A quasi-experimental trial was conducted to compare the effect on information recall of : ( a ) the use of adjunct questions ( AQ ) in printed material s ; and ( b ) a procedure ( the 5Rs ) for integrating printed patient education material s into face-to-face teaching . A total of 51 patients with severe left ventricular failure ( cardiomyopathy ) was assigned to one of three groups ( n=17 ) . Each group worked with a purpose -prepared booklet , the first in association with the 5Rs procedure ; the second group with a version of the booklet containing adjunct questions ; and the third with a text only version of the booklet . Recall of information from the booklet was measured using a checklist scored on the basis of responses secured in a st and ardised interview . Improved recall was associated with both the adjunct questions and the 5Rs procedure , with the latter achieving a substantially superior outcome . The practical implication s of these findings are presented and directions for further research indicated The effect of adjunct questions on the amount of information retained from the reading of a patient education booklet was investigated experimentally . Ninety older adults ( mean age 77 years ) were assigned r and omly to a treatment , treatment control or non-treatment control group , 30 in each . The treatment condition was established by having subjects spend 30 min with a booklet about post-operative eye care . The booklet included four sets of review questions . The treatment control group spent the same period with a booklet which was identical apart from the questions . Knowledge of eye care was measured using a checklist scored on the basis of responses secured in a st and ardised interview . Although the two treatment groups decisively outperformed the control group on the measure , no effect attributable to the adjunct questions was detected . Factors which might account for this outcome are discussed . Directions for further research and implication s for practice are indicated Over recent years , specialist breast care nurses have become increasingly recognized as core members of any breast care team within the UK . Part of the role is to support patients at the highly stressful stage of receiving a diagnosis . This paper describes an ' advocacy ' style of nurse counsellor intervention which aims to improve patients ' preparation for , and involvement in , the diagnostic consultation and provides a framework for future counselling support . One hundred and three women undergoing surgery following diagnosis of breast cancer or a benign breast lump were supported using either this advocacy intervention or a more conventional model of care . The aim was to identify the most effective and appropriate method of intervening at this important stage . Assessment took place before surgery , with 2-week and 6-month follow-ups , and included the Hospital Anxiety and Depression Scale , Rotterdam Symptom Check List and semi-structured interviews addressing perceived quality of care , involvement in decision-making and psycho-social functioning . Whilst the results of many measures were similar for women in the two intervention groups , qualitative data support the implementation of the advocacy method by the breast care nurse The authors investigated the effect of giving written material on information recall from informed consent counselling for cataract surgery . Fifty English-speaking patients who underwent non-urgent cataract extraction at Flinders Medical Centre , South Australia , were prospect ively enrolled . Systematic counselling for cataract surgery was provided , with a written copy of the content given to a r and omly selected group of patients ( n = 24 ) . All subjects completed a question naire after counselling and again at two weeks after surgery to test their satisfaction with , and recall of , information provided . Patients were found to be satisfied with the amount of information they received and most were able to recall details about the cataract surgery procedure . However , many could not recall success rates or complication rates and only a minority could list any complication . The provision of written information did not significantly alter recall ( p>0.05 ) . Recall was significantly better immediately after counselling than two weeks after surgery ( p<0.05 ) . Younger patients also had significantly better recall ( p<0.05 ) . Patients were happy with the information they had been given but did not remember enough from the informed consent process to satisfy legal requirements PURPOSE Despite reports of poor patient underst and ing and recall after cancer consultations , few doctors provide communication aids . We conducted a r and omized trial comparing an audiotape of the consultation versus individualized summary letters to patients after their first consultation with a medical oncologist . METHODS One hundred eighty-two cancer patients were r and omized to receive either ( 1 ) the audiotape followed 7 to 10 days later by the letter or ( 2 ) the letter followed by the audiotape . Outcome measures included patient recall , anxiety and depression , satisfaction with and use of the communication aids , and patient preferences for six communication options . Demographic and disease variables and information and involvement preferences were documented . RESULTS Eighty percent of patients wanted all information and 72 % wanted to participate in treatment decisions . Patients listened to the tape on average 2.3 times and read the letter 2.8 times over 4 weeks , and 90 % showed the tape or letter to a friend , relative , or doctor . Satisfaction with the tape and letter were uniformly high and they did not differentially affect recall , anxiety , or depression . When asked to rank six communication options , 46 % of patients gave the highest rank to the tape and 21 % to the letter . CONCLUSION Patients use audiotapes of their cancer consultation and individualized letters to review the information given and communicate information to relatives and friends . They prefer audiotapes to letters . Clinicians should consider installing audiotape-recording facilities that could be used to tape new-patient consultations |
12,481 | 29,982,523 | Provider price display in electronic health record environment did not consistently influence domains of healthcare quality such as efficiency , effectiveness and patient safety .
Conclusions Published evidence suggests that price display tools aim ed at ordering providers in EHR/CPOE do not influence the efficiency domain of healthcare quality .
Scant published evidence suggests that they do not influence the effectiveness and patient safety domains of healthcare quality . | Objective To study the association between Electronic Health Record (EHR)/Computerized Physician Order Entry ( CPOE ) provider price display , and domains of healthcare quality ( efficiency , effective care , patient centered care , patient safety , equitable care , and timeliness of care ) . | OBJECTIVE We sought to determine whether information on hospital charges ( prices ) would affect test-ordering and quality of patient care in a pediatric emergency department ( ED ) . DESIGN Prospect i ve , nonblind , controlled trial of price information . SETTING Urban , university-affiliated pediatric ED . METHODS We prospect ively assessed patients 2 months to 10 years of age with a presenting temperature > /=38.5 degrees C or complaint of vomiting , diarrhea , or decreased oral intake . The assessment s were done during three periods : September 1997 through December 1997 ( control ) , January 1998 through March 1998 ( intervention ) , and April 1998 ( washout ) . In the control and washout periods , physicians noted tests ordered on a list attached to each chart . In the intervention period , physicians noted tests ordered on a similar list that included st and ard hospital charges for each test . Records of each visit were review ed to determine clinical and demographic information as well as patient disposition . In the control and intervention periods , families of nonadmitted patients were interviewed by telephone 7 days after the visit . RESULTS When controlled for triage level , vital signs , and admission rates , in a multivariate model , charges for tests in the intervention period were 27 % less than charges in the control period . The greatest decrease was seen among low-acuity , nonadmitted patients ( 43 % ) . In telephone follow-up , patients in the intervention period were slightly more likely to have made an unscheduled follow-up visit to a health care provider ( 24.4 % vs 17.8 % ) , but did not differ on improved condition ( 86.7 % vs 83.4 % ) or family satisfaction ( 93.8 % vs 93.0 % ) . Adjusted charges in the washout period were 15 % lower than in the control period and 15 % higher than in the intervention period . CONCLUSION Providing price information was associated with a significant reduction in charges for tests ordered on pediatric ED patients with acute illness not requiring admission . This decrease was associated with a slightly higher rate of unscheduled follow-up , but no difference in subjective outcomes or family satisfaction Background Prior studies have demonstrated how price transparency lowers the test-ordering rates of trainees in hospitals , and physician-targeted price transparency efforts have been viewed as a promising cost-controlling strategy . Objective To examine the effect of displaying paid-price information on test-ordering rates for common imaging studies and procedures within an accountable care organization ( ACO ) . Design Block r and omized controlled trial for 1 year . SubjectsA total of 1205 fully licensed clinicians ( 728 primary care , 477 specialists ) . InterventionS tarting January 2014 , clinicians in the Control arm received no price display ; those in the intervention arms received Single or Paired Internal/External Median Prices in the test-ordering screen of their electronic health record . Internal prices were the amounts paid by insurers for the ACO ’s services ; external paid prices were the amounts paid by insurers for the same services when delivered by unaffiliated providers . Main Measures Ordering rates ( orders per 100 face-to-face encounters with adult patients ): overall , design ated to be completed internally within the ACO , considered “ inappropriate ” ( e.g. , MRI for simple headache ) , and thought to be “ appropriate ” ( e.g. , screening colonoscopy).Key Results We found no significant difference in overall ordering rates across the Control , Single Median Price , or Paired Internal/External Median Prices study arms . For every 100 encounters , clinicians in the Control arm ordered 15.0 ( SD 31.1 ) tests , those in the Single Median Price arm ordered 15.0 ( SD 16.2 ) tests , and those in the Paired Prices arms ordered 15.7 ( SD 20.5 ) tests ( one-way ANOVA p-value 0.88 ) . There was no difference in ordering rates for tests design ated to be completed internally or considered to be inappropriate or appropriate . Conclusions Displaying paid-price information did not alter how frequently primary care and specialist clinicians ordered imaging studies and procedures within an ACO . Those with a particular interest in removing waste from the health care system may want to consider a variety of context ual factors that can affect physician-targeted price transparency PURPOSE The aim of this study was to determine whether presenting providers with cost information at the point of order entry significantly influences imaging utilization . METHODS Using data from fiscal year 2007 , the 10 most frequently ordered imaging tests were identified . Five of these were r and omly assigned to the active cost display group and 5 to the control group . During a 6-month baseline period from November 10 , 2008 , to May 9 , 2009 , no costs were displayed . During a seasonally matched intervention period from November 10 , 2009 , to May 9 , 2010 , costs were displayed only for tests in the active group . At the conclusion of the study , the radiology information system was queried to determine the number of orders executed for all tests during both periods . The main outcome measure was the mean relative utilization change between the control and intervention periods for the active group vs the control group . An additional measure was the correlation between test cost and utilization change in the active group vs the control group . RESULTS The mean utilization change was + 2.8 ± 4.4 % for the active group and -3.0 ± 5.5 % for the control group , with no significant difference between the two groups ( P = .10 , Student 's t-test ) . There was also no significant difference in the correlation between test cost and utilization change for the active group vs the control group ( P = .25 , Fisher 's z-test ) . On the basis of the observed st and ard deviations , this study had 90 % power to detect an 11.8 % difference in mean relative utilization change between groups . CONCLUSIONS Provider cost transparency alone does not significantly influence inpatient imaging utilization Objectives To determine the impact of systemwide charge display on laboratory utilization . Methods This was a r and omized controlled trial with a baseline period and an intervention period . Tests were r and omized to a control arm or an active arm . The maximum allowable Medicare reimbursement rate was displayed for tests in the active arm during the intervention period . Total volume of tests in the active arm was compared with those in the control arm . Residents were surveyed before and after the intervention to assess charge awareness . Results Charge display had no effect on order behavior . This result held for patient type ( inpatient vs outpatient ) and for insurance category ( commercial , government , self-pay ) . Residents overestimated the charges of tests both before and after the intervention . Many residents failed to notice the charge display in the computerized order entry system . Conclusions The impact of charge display depends on context . Charge display is not always effective OBJECTIVE To assess the effects on health care re source utilization of a network of microcomputer workstations for writing all inpatient orders . DESIGN R and omized controlled clinical trial . SETTING Inpatient internal medicine service of an urban public hospital . SUBJECTS A total of 5219 internal medicine patients and the 68 teams of house officers , medical students , and faculty internists who cared for them . INTERVENTION Microcomputer workstations , linked to a comprehensive electronic medical record system , for writing all inpatient orders . MAIN OUTCOME MEASURES Total inpatient charges for each admission and charges for specific categories of orders . A time-motion study of selected interns assessed the ordering system 's time consumption . RESULTS Intervention teams generated charges that were $ 887 ( 12.7 % ) lower per admission than did control teams ( P = .02 ) . Significant reductions ( P < .05 ) were demonstrated separately for bed charges , diagnostic test charges , and drug charges . Reductions of similar proportion and statistical significance were found for hospital costs . The mean length of stay was 0.89 day shorter for intervention resident teams ( P = .11 ) . Interns in the intervention group spent an average of 33 minutes longer ( 5.5 minutes per patient ) during a 10-hour observation period writing orders than did interns in the control group ( P < .0001 ) . CONCLUSIONS A network of microcomputer workstations for writing all inpatient orders significantly lowered patient charges and hospital costs . This would amount to savings of more than $ 3 million in charges annually for this hospital 's medicine service and potentially tens of billions of dollars nationwide . However , the system required more physician time than did the paper charts . Research at other sites and system advances to reduce time requirements are warranted BACKGROUND AND OBJECTIVES : Ordering rates for imaging studies and procedures may change if clinicians are shown the prices of those tests while they are ordering . We studied the effect of 2 forms of paid price information , single median price and paired internal/external median prices , on how often pediatric-focused and adult-oriented clinicians ( most frequently general pediatricians and adult specialists caring for pediatric-aged patients , respectively ) order imaging studies and procedures for 0- to 21-year-olds . METHODS : In January 2014 , we r and omized 227 pediatric-focused and 279 adult-oriented clinicians to 1 of 3 study arms : Control ( no price display ) , Single Median Price , or Paired Internal/External Median Prices ( both with price display in the ordering screen of electronic health record ) . We used 1-way analysis of variance and paired t tests to examine how frequently clinicians ( 1 ) placed orders and ( 2 ) design ated tests to be completed internally within an accountable care organization . RESULTS : For pediatric-focused clinicians , there was no significant difference in the rates at which orders were placed or design ated to be completed internally across the study arms . For adult-oriented clinicians caring for children and adolescents , however , those in the Single Price and Paired Price arms placed orders at significantly higher rates than those in the Control group ( Control 3.2 [ SD 4.8 ] , Single Price 6.2 [ SD 6.8 ] , P < .001 and Paired Prices 5.2 [ SD 7.9 ] , P = .04 ) . The rate at which adult-oriented clinicians design ated tests to be completed internally was not significantly different across arms . CONCLUSIONS : The effect of price information on ordering rates appears to depend on whether the clinician is pediatric-focused or adult-oriented We studied the effect of informing physicians of the charges for outpatient diagnostic tests on their ordering of such tests in an academic primary care medical practice . All tests were ordered at microcomputer workstations by 121 physicians . For half ( the intervention group ) , the charge for the test being ordered and the total charge for tests for that patient on that day were displayed on the computer screen . The remaining physicians ( control group ) also used the computers but received no message about charges . The primary outcomes measured were the number of tests ordered and the charges for tests per patient visit . In the 14 weeks before the study , the number of tests ordered and the average charge for tests per patient visit were similar for the intervention and control groups . During the 26-week intervention period , the physicians in the intervention group ordered 14 percent fewer tests per patient visit than did those in the control group ( P less than 0.005 ) , and the charges for tests were 13 percent ( $ 6.68 per visit ) lower ( P less than 0.05 ) . The differences were greater for scheduled visits ( 17 percent fewer tests and 15 percent lower charges for the intervention group ; P less than 0.01 ) than for unscheduled ( urgent ) visits ( 11 percent fewer tests and 10 percent lower charges ; P greater than 0.3 ) . During the 19 weeks after the intervention ended , the number of tests ordered by the physicians in the intervention group was only 7.7 percent lower than the number ordered by the physicians in the control group , and the charges for tests were only 3.5 percent lower ( P greater than 0.3 ) . Three measures of possible adverse outcomes --number of hospitalizations , emergency room visits , and outpatient visits during the study period and the following six months -- were similar for the patients seen by the physicians in both groups . We conclude that displaying the charges for diagnostic tests significantly reduced the number and cost of tests ordered , especially for patients with scheduled visits . The effects of this intervention did not persist after it was discontinued Objectives The aim of this study was to establish whether price list information could reduce laboratory and radiological examination costs in emergency departments ( EDs ) . Material s and methods A prospect i ve survey of adult ( > 16 years old ) admissions was conducted at the ED of a university hospital in Belgium . Nine resident emergency physicians were followed for a span of 6 months , which was divided into 2-month periods : control ( October and November 2011 ) , intervention ( December 2011 to January 2012 ) , and washout ( February and March 2012 ) . Laboratory and radiological costs for each of the daily admissions were calculated during the respective periods and compared . Results A total of 3758 patients were registered : 1093 in period 1 ( control ) , 1329 in period 2 ( intervention ) , and 1336 in period 3 ( washout ) . We observed significant reductions in examination costs : 10.73 % ( P=0.015 ) for laboratory and 33.66 % ( P<0.001 ) for radiological costs in period 2 versus period 1 ; 5.02 % ( P=0.014 ) for laboratory and 40.00 % ( P<0.001 ) for radiological costs in period 3 versus period 1 . In addition , we found that laboratory examination costs increased slightly between periods 2 and 3 ( + 6.4 % ) , whereas costs related to radiologic examinations continued to decrease ( −10.16 % ) ; however , these differences were not statistically significant . Conclusion We conclude that the distribution of price lists at EDs promotes cost awareness , which can result in significant decreases in examination costs Objective Reference tests , also known as send-out tests , are commonly ordered laboratory tests with variable costs and turn-around times . We aim to examine the effects of displaying reference laboratory costs and turn-around times during computerised physician order entry ( CPOE ) on inpatient physician ordering behaviour . Design We conducted a prospect i ve observational study at a tertiary care hospital involving inpatient attending physicians and residents . Physician ordering behaviour was prospect ively observed between September 2010 and December 2012 . An intervention was implemented to display cost and turn-around time for reference tests within our CPOE . We examined changes in the mean number of monthly physician orders per inpatient day at risk , the mean cost per order , and the average turn-around time per order . Results After our intervention , the mean number of monthly physician orders per inpatient day at risk decreased by 26 % ( 51 vs 38 , p<0.0001 ) with a decrease in mean cost per order ( US$ 146.50 vs US$ 134.20 , p=0.0004 ) . There were no significant differences in mean turn-around time per order ( 5.6 vs 5.7 days , p=0.057 ) . A stratified analysis of both cost and turn-around time showed significant decreases in physician ordering . The intervention projected a mean annual savings of US$ 330 439 . Reference test cost and turn-around time variables were poorly correlated ( r=0.2 ) . These findings occurred in the setting of non-significant change to physician ordering in a control cohort of non-reference laboratory tests . Conclusions Display of reference laboratory cost and turn-around time data during real-time ordering may result in significant decreases in ordering of reference laboratory tests with subsequent cost savings OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND The computerized display of charges for ancillary tests in out patients has been found to affect physician-ordering behavior , but this issue has not been studied in in patients . OBJECTIVE To assess whether the computerized display of charges for clinical laboratory or radiological tests affected physician-ordering behavior . PATIENTS AND METHODS Two prospect i ve controlled trials , r and omized by patient , were performed . Each trial included all medical and surgical in patients at 1 large teaching hospital during 4 and 7 months : 3536 intervention and 3554 control in patients in the group with clinical laboratory tests , and 8728 intervention and 8653 control in patients in the group with radiological tests . The intervention consisted of the computerized display of charges for tests at the time of ordering . MAIN OUTCOME MEASURES The number of clinical laboratory and radiological tests ordered per admission and the charges for these tests . RESULTS For the clinical laboratory tests , during a 4-month study period , patients in the intervention group had 4.5 % fewer tests ordered , and the total charges for these tests were 4.2 % lower , although neither difference was statistically significant . Compared with historical controls from the same 4-month period a year before , the charges for the tests per admission had decreased 13.3 % , but the decrease was temporally correlated with a restriction of future ordering of tests , and not with the introduction of the display of charges . For the radiological tests , during a 7-month period , the intervention group had almost identical numbers of tests ordered and charges for these tests . CONCLUSIONS The computerized display of charges had no statistically significant effect on the number of clinical laboratory tests or radiological procedures ordered or performed , although small trends were present for clinical laboratory tests . More intensive interventions may be needed to affect physician test utilization IMPORTANCE Inpatient care providers often order laboratory tests without any appreciation for the costs of the tests . OBJECTIVE To determine whether we could decrease the number of laboratory tests ordered by presenting providers with test fees at the time of order entry in a tertiary care hospital , without adding extra steps to the ordering process . DESIGN Controlled clinical trial . SETTING Tertiary care hospital . PARTICIPANTS All providers , including physicians and nonphysicians , who ordered laboratory tests through the computerized provider order entry system at The Johns Hopkins Hospital . INTERVENTION We r and omly assigned 61 diagnostic laboratory tests to an " active " arm ( fee displayed ) or to a control arm ( fee not displayed ) . During a 6-month baseline period ( November 10 , 2008 , through May 9 , 2009 ) , we did not display any fee data . During a 6-month intervention period 1 year later ( November 10 , 2009 , through May 9 , 2010 ) , we displayed fees , based on the Medicare allowable fee , for active tests only . MAIN OUTCOME MEASURES We examined changes in the total number of orders placed , the frequency of ordered tests ( per patient-day ) , and total charges associated with the orders according to the time period ( baseline vs intervention period ) and by study group ( active test vs control ) . RESULTS For the active arm tests , rates of test ordering were reduced from 3.72 tests per patient-day in the baseline period to 3.40 tests per patient-day in the intervention period ( 8.59 % decrease ; 95 % CI , -8.99 % to -8.19 % ) . For control arm tests , ordering increased from 1.15 to 1.22 tests per patient-day from the baseline period to the intervention period ( 5.64 % increase ; 95 % CI , 4.90 % to 6.39 % ) ( P < .001 for difference over time between active and control tests ) . CONCLUSIONS AND RELEVANCE Presenting fee data to providers at the time of order entry result ed in a modest decrease in test ordering . Adoption of this intervention may reduce the number of inappropriately ordered diagnostic tests Importance Many health systems are considering increasing price transparency at the time of order entry . However , evidence of its impact on clinician ordering behavior is inconsistent and limited to single-site evaluations of shorter duration . Objective To test the effect of displaying Medicare allowable fees for inpatient laboratory tests on clinician ordering behavior over 1 year . Design , Setting , and Participants The Pragmatic R and omized Introduction of Cost data through the electronic health record ( PRICE ) trial was a r and omized clinical trial comparing a 1-year intervention to a 1-year preintervention period , and adjusting for time trends and patient characteristics . The trial took place at 3 hospitals in Philadelphia between April 2014 and April 2016 and included 98 529 patients comprising 142 921 hospital admissions . Interventions Inpatient laboratory test groups were r and omly assigned to display Medicare allowable fees ( 30 in intervention ) or not ( 30 in control ) in the electronic health record . Main Outcomes and Measures Primary outcome was the number of tests ordered per patient-day . Secondary outcomes were tests performed per patient-day and Medicare associated fees . Results The sample included 142 921 hospital admissions representing patients who were 51.9 % white ( 74 165 ) , 38.9 % black ( 55 526 ) , and 56.9 % female ( 81 291 ) with a mean ( SD ) age of 54.7 ( 19.0 ) years . Preintervention trends of order rates among the intervention and control groups were similar . In adjusted analyses of the intervention group compared with the control group over time , there were no significant changes in overall test ordering behavior ( 0.05 tests ordered per patient-day ; 95 % CI , −0.002 to 0.09 ; P = .06 ) or associated fees ( $ 0.24 per patient-day ; 95 % CI , −$0.42 to $ 0.91 ; P = .47 ) . Exploratory subset analyses found small but significant differences in tests ordered per patient-day based on patient intensive care unit ( ICU ) stay ( patients with ICU stay : −0.16 ; 95 % CI , −0.31 to −0.01 ; P = .04 ; patients without ICU stay : 0.13 ; 95 % CI , 0.08 - 0.17 ; P < .001 ) and the magnitude of associated fees ( top quartile of tests based on fee value : −0.01 ; 95 % CI , −0.02 to −0.01 ; P = .04 ; bottom quartile : 0.03 ; 95 % CI , 0.002 - 0.06 ; P = .04 ) . Adjusted analyses of tests that were performed found a small but significant overall increase in the intervention group relative to the control group over time ( 0.08 tests performed per patient day , 95 % CI , 0.03 - 0.12 ; P < .001 ) . Conclusions and Relevance Displaying Medicare allowable fees for inpatient laboratory tests did not lead to a significant change in overall clinician ordering behavior or associated fees . Trial Registration clinical trials.gov Identifier : OBJECTIVE We aim ed to assess the trends in prescribed defined daily doses ( DDD ) and drug expenses before and after the introduction of a computerized cost containment module into the computer record system of a defined group of GPs . The GPs ' expectations for and experiences with the module were examined . METHOD We performed a controlled follow-up study on antecedent data before and after intervention . A question naire was administered to the intervention group at the introduction and 1 year later . Data on prescribing were collected in the data base of the Health Insurance Aarhus County , as a normal routine for accounting . The GPs were not aware of the ongoing cost supervision study . Additional cost information software was introduced on 1 January 1993 to 20 practice s with 28 GPs . The software assisted the GPs in a semiautomatic way to identify and prescribe the cheapest drugs . The subjects comprised 158 practice s including 231 GPs in Aarhus County , Denmark . Question naires were sent to the 20 intervention practice s. The main outcome measures were prescribed DDD , reimbursement for prescribed drugs , and reimbursement per prescribed DDD quarterly during 1992 and 1993 . RESULTS Compared with the controls there were no changes in prescribed DDD , reimbursement for prescribed drugs , and reimbursement per prescribed DDD in the intervention group after the introduction of the module . CONCLUSION Simply giving a r and om group of GPs computer assistance to choose less expensive drugs did not reduce expenditure per DDD . Cost containment procedures should be more intensive than just giving the doctors a computer-assisted decision aid |
12,482 | 30,443,007 | In conclusion , empagliflozin reduces systolic and diastolic blood pressure , uric acid , hemoglobin A1c , fasting plasma glucose , and body weight .
These data suggest the beneficial effects of empagliflozin on these cardiovascular risk factors in patients with type 2 diabetes mellitus | The antidiabetic effect of empagliflozin in patients with type 2 diabetes mellitus has been explored in several trials .
We performed this meta- analysis determining the effects of empagliflozin on blood pressure , uric acid , estimated glomerular filtration rate , blood lipids , blood glucose , and body weight in patients with type 2 diabetes mellitus . | Patients with type 2 diabetes mellitus ( T2DM ) with a glycated haemoglobin ( HbA1c ) level ≥7 and ≤10 % were r and omized to receive empagliflozin 12.5 mg twice daily ( n = 219 ) , 25 mg once daily ( n = 218 ) , 5 mg twice daily ( n = 219 ) or 10 mg once daily ( n = 220 ) , or placebo ( n = 107 ) as add‐on to stable‐dose metformin immediate release ( IR ) twice daily for 16 weeks . The primary endpoint was change from baseline in HbA1c at week 16 . At week 16 , change from baseline in HbA1c with empagliflozin twice daily was non‐inferior to empagliflozin once daily and vice versa . The adjusted mean ( 95 % confidence interval ) difference in change from baseline in HbA1c with empagliflozin 12.5 mg twice daily versus 25 mg once daily was −0.11 % ( −0.26 , 0.03 ) , and with empagliflozin 5 mg twice daily versus 10 mg once daily it was −0.02 % ( −0.16 , 0.13 ) . All empagliflozin regimens were well tolerated ; thus , when used as add‐on to metformin IR in patients with T2DM , the therapeutic effect of empagliflozin twice‐daily and once‐daily regimens can be considered equivalent Background and Purpose — In the EMPA-REG OUTCOME trial ( Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients ) , empagliflozin added to st and ard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events , driven by a reduction in cardiovascular mortality , with no significant difference between empagliflozin and placebo in risk of myocardial infa rct ion or stroke . In a modified intent-to-treat analysis , the hazard ratio for stroke was 1.18 ( 95 % confidence interval , 0.89–1.56 ; P=0.26 ) . We further investigated cerebrovascular events . Methods — Patients were r and omized to empagliflozin 10 mg , empagliflozin 25 mg , or placebo ; 7020 patients were treated . Median observation time was 3.1 years . Results — The numeric difference in stroke between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event > 90 days after last intake of study drug ( versus 3 on placebo ) . In a sensitivity analysis based on events during treatment or ⩽90 days after last dose of drug , the hazard ratio for stroke with empagliflozin versus placebo was 1.08 ( 95 % confidence interval , 0.81–1.45 ; P=0.60 ) . There were no differences in risk of recurrent , fatal , or disabling strokes , or transient ischemic attack , with empagliflozin versus placebo . Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke . Conclusions — In patients with type 2 diabetes mellitus and high cardiovascular risk , there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01131676 OBJECTIVE To investigate the efficacy , safety , and tolerability of empagliflozin in patients with type 2 diabetes and hypertension . RESEARCH DESIGN AND METHODS Patients ( N = 825 ) with type 2 diabetes and hypertension ( mean seated systolic blood pressure [ SBP ] 130–159 mmHg and diastolic blood pressure [ DBP ] 80–99 mmHg ) were r and omized ( double blind ) to 10 mg or 25 mg empagliflozin or placebo once daily for 12 weeks . RESULTS At week 12 , adjusted mean difference versus placebo in change from baseline in mean 24-h SBP ( ambulatory blood pressure monitoring [ ABPM ] ) was −3.44 mmHg ( 95 % CI −4.78 , −2.09 ) with 10 mg empagliflozin and −4.16 mmHg ( −5.50 , −2.83 ) with 25 mg empagliflozin ( both P < 0.001 ) . At week 12 , adjusted mean difference versus placebo in change from baseline in mean 24-h DBP ( ABPM ) was −1.36 mmHg ( 95 % CI −2.15 , −0.56 ) with 10 mg empagliflozin and −1.72 mmHg ( 95 % CI −2.51 , −0.93 ) with 25 mg empagliflozin ( both P < 0.001 ) . Changes in office BP were consistent with ABPM . Adjusted mean difference versus placebo in change from baseline in HbA1c at week 12 was −0.62 % ( 95 % CI −0.72 , −0.52 ) ( −6.8 mmol/mol [ 95 % CI −7.9 , −5.7 ] ) with 10 mg empagliflozin and −0.65 % ( 95 % CI −0.75 , −0.55 ) ( −7.1 mmol/mol [ 95 % CI −8.2 , −6.0 ] ) with 25 mg empagliflozin ( both P < 0.001 ) . Empagliflozin was well tolerated . One patient on placebo and one patient on 10 mg empagliflozin reported events consistent with volume depletion . CONCLUSIONS Empagliflozin was associated with significant and clinical ly meaningful reductions in BP and HbA1c versus placebo and was well tolerated in patients with type 2 diabetes and hypertension Background This study evaluated the effect of empagliflozin on postpr and ial glucose ( PPG ) and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Methods Patients ( N = 60 ; baseline mean [ SD ] HbA1c 7.91 [0.80]% ; body mass index 24.3 [ 3.2 ] kg/m2 ) were r and omized to receive empagliflozin 10 mg ( n = 20 ) , empagliflozin 25 mg ( n = 19 ) or placebo ( n = 21 ) once daily as monotherapy for 28 days . A meal tolerance test and continuous glucose monitoring ( CGM ) for 24 hours were performed at baseline and on days 1 and 28 . The primary endpoint was change from baseline in area under the glucose concentration-time curve 3 hours after breakfast ( AUC1–4h for PPG ) at day 28 . Results Adjusted mean ( 95 % ) differences versus placebo in changes from baseline in AUC1 - 4h for PPG at day 1 were −97.1 ( −126.5 , −67.8 ) mg · h/dl with empagliflozin 10 mg and −91.6 ( −120.4 , −62.8 ) mg · h/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) and at day 28 were −85.5 ( −126.0 , −45.0 ) mg · h/dl with empagliflozin 10 mg and −104.9 ( −144.8 , −65.0 ) mg · h/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) . Adjusted mean ( 95 % CI ) differences versus placebo in change from baseline in 24-hour mean glucose ( CGM ) at day 1 were −20.8 ( −27.0 , −14.7 ) mg/dl with empagliflozin 10 mg and −23.9 ( −30.0 , −17.9 ) mg/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) and at day 28 were −24.5 ( −35.4 , −13.6 ) mg/dl with empagliflozin 10 mg and −31.7 ( −42.5,-20.9 ) mg/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) . Changes from baseline in mean amplitude of glucose excursions ( MAGE ; CGM ) were not significantly different with either empagliflozin dose versus placebo at either timepoint . Curves of mean glucose ( CGM ) did not change between baseline and day 1 or 28 with placebo , but shifted downward with empagliflozin . Percentage of time with glucose ≥70 to < 180 mg/dl increased from 52.0 % at baseline to 77.0 % at day 28 with empagliflozin 10 mg and from 55.0 % to 81.1 % with empagliflozin 25 mg , without increasing time spent with hypoglycemia . Conclusion Empagliflozin for 28 days reduced PPG from the first day and improved daily blood glucose control in Japanese patients with T2DM.Trial registration Clinical trials.gov OBJECTIVE We investigated the efficacy and safety of the sodium glucose cotransporter 2 inhibitor , empagliflozin , added to multiple daily injections of insulin ( MDI insulin ) in obese patients with type 2 diabetes mellitus ( T2DM ) . RESEARCH DESIGN AND METHODS Patients inadequately controlled on MDI insulin ± metformin ( mean HbA1c 8.3 % [ 67 mmol/mol ] ; BMI 34.8 kg/m2 ; insulin dose 92 international units/day ) were r and omized and treated with once-daily empagliflozin 10 mg ( n = 186 ) , empagliflozin 25 mg ( n = 189 ) , or placebo ( n = 188 ) for 52 weeks . Insulin dose was to remain stable in weeks 1–18 , adjusted to meet glucose targets in weeks 19–40 , then stable in weeks 41–52 . The primary end point was change from baseline in HbA1c at week 18 . Secondary end points were changes from baseline in insulin dose , weight , and HbA1c at week 52 . RESULTS Adjusted mean ± SE changes from baseline in HbA1c were −0.50 ± 0.05 % ( −5.5 ± 0.5 mmol/mol ) for placebo versus −0.94 ± 0.05 % ( −10.3 ± 0.5 mmol/mol ) and −1.02 ± 0.05 % ( −11.1 ± 0.5 mmol/mol ) for empagliflozin 10 mg and empagliflozin 25 mg , respectively , at week 18 ( both P < 0.001 ) . At week 52 , further reductions with insulin titration result ed in changes from baseline in HbA1c of −0.81 ± 0.08 % ( −8.9 ± 0.9 mmol/mol ) , −1.18 ± 0.08 % ( −12.9 ± 0.9 mmol/mol ) , and −1.27 ± 0.08 % ( −13.9 ± 0.9 mmol/mol ) with placebo , empagliflozin 10 mg , and empagliflozin 25 mg , respectively , and final HbA1c of 7.5 % ( 58 mmol/mol ) , 7.2 % ( 55 mmol/mol ) , and 7.1 % ( 54 mmol/mol ) , respectively . More patients attained HbA1c < 7 % ( < 53 mmol/mol ) with empagliflozin ( 31–42 % ) versus placebo ( 21 % ; both P < 0.01 ) . Empagliflozin 10 mg and empagliflozin 25 mg reduced insulin doses ( −9 to −11 international units/day ) and weight ( −2.4 to −2.5 kg ) versus placebo ( all P < 0.01 ) at week 52 . CONCLUSIONS In obese , difficult-to-treat patients with T2DM inadequately controlled on high MDI insulin doses , empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements OBJECTIVE To investigate the efficacy and tolerability of empagliflozin as add-on to metformin and sulfonylurea in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Patients inadequately controlled on metformin and sulfonylurea ( HbA1c ≥7 to ≤10 % ) were r and omized and treated with once-daily empagliflozin 10 mg ( n = 225 ) , empagliflozin 25 mg ( n = 216 ) , or placebo ( n = 225 ) for 24 weeks . The primary end point was change from baseline in HbA1c at week 24 . Key secondary end points were changes from baseline in weight and mean daily glucose ( MDG ) at week 24 . RESULTS At week 24 , adjusted mean ( SE ) changes from baseline in HbA1c were −0.17 % ( 0.05 ) for placebo vs. −0.82 % ( 0.05 ) and −0.77 % ( 0.05 ) for empagliflozin 10 and 25 mg , respectively ( both P < 0.001 ) . Empagliflozin significantly reduced MDG , weight , and systolic ( but not diastolic ) blood pressure versus placebo . Adverse events were reported in 62.7 , 67.9 , and 64.1 % of patients on placebo and empagliflozin 10 and 25 mg , respectively . Events consistent with urinary tract infection were reported in 8.0 , 10.3 , and 8.3 % of patients on placebo and empagliflozin 10 and 25 mg , respectively ( females : 13.3 , 18.0 , and 17.5 % , respectively ; males : 2.7 , 2.7 , and 0 % , respectively ) . Events consistent with genital infection were reported in 0.9 , 2.7 , and 2.3 % of patients on placebo and empagliflozin 10 and 25 mg , respectively ( females : 0.9 , 4.5 , and 3.9 % , respectively ; males : 0.9 % in each group ) . CONCLUSIONS Empagliflozin 10 and 25 mg for 24 weeks as add-on to metformin plus sulfonylurea improved glycemic control , weight , and systolic blood pressure and were well tolerated AIMS Dapagliflozin , a highly selective inhibitor of sodium-glucose cotransporter 2 ( SGLT2 ) , reduces hyperglycaemia and weight in patients with type 2 diabetes mellitus ( T2DM ) by increasing urinary glucose excretion . Long-term glycaemic control , body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment . METHODS This r and omized , double-blind , placebo-controlled study ( NCT00855166 ) enrolled patients with T2DM [ mean : age 60.7 years ; HbA1c 7.2 % ; body mass index ( BMI ) 31.9 kg/m(2 ) ; body weight 91.5 kg ] inadequately controlled on metformin . Patients ( N = 182 ) were r and omly assigned 1 : 1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period . At week 102 , changes from baseline in HbA1c , weight , waist circumference , total body fat mass as measured by dual-energy X-ray absorptiometry ( DXA ) , serum markers of bone turnover , bone mineral density ( BMD ) as measured by DXA , and adverse events were evaluated . RESULTS A total of 140 patients ( 76.9 % ) completed the study . Over 102 weeks , dapagliflozin-treated patients showed reductions in HbA1c by -0.3 % , weight by -4.54 kg , waist circumference by -5.0 cm and fat mass by -2.80 kg without increase in rate of hypoglycaemia . Compared with placebo , no meaningful changes from baseline in markers of bone turnover or BMD were identified over 102 weeks . One fracture occurred in each treatment group . The frequency of urinary tract infection ( UTI ) and genital infection was similar in both treatment groups . CONCLUSIONS Over 102 weeks , dapagliflozin improved glycaemic control , and reduced weight and fat mass , without affecting markers of bone turnover or BMD in patients with T2DM inadequately controlled on metformin Aims To investigate the efficacy and tolerability of empagliflozin added to basal insulin‐treated type 2 diabetes . Methods Patients inadequately controlled [ glycated haemoglobin ( HbA1c ) > 7 to ≤10 % ( > 53 to ≤86 mmol/mol ) ] on basal insulin ( glargine , detemir , NPH ) were r and omized to empagliflozin 10 mg ( n = 169 ) , empagliflozin 25 mg ( n = 155 ) or placebo ( n = 170 ) for 78 weeks . The baseline characteristics were balanced among the groups [ mean HbA1c 8.2 % ( 67 mmol/mol ) , BMI 32.2 kg/m2 ] . The basal insulin dose was to remain constant for 18 weeks , then could be adjusted at investigator 's discretion . The primary endpoint was change from baseline in HbA1c at week 18 . Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78 . Results At week 18 , the adjusted mean ± st and ard error changes from baseline in HbA1c were 0.0 ± 0.1 % ( −0.1 ± 0.8 mmol/mol ) for placebo , compared with −0.6 ± 0.1 % ( −6.2 ± 0.8 mmol/mol ) and −0.7 ± 0.1 % ( −7.8 ± 0.8 mmol/mol ) for empagliflozin 10 and 25 mg , respectively ( both p < 0.001 ) . At week 78 , empagliflozin 10 and 25 mg significantly reduced HbA1c , insulin dose and weight vs placebo ( all p < 0.01 ) , and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo ( p = 0.004 ) . Similar percentages of patients had confirmed hypoglycaemia in all groups ( 35–36 % ) . Events consistent with urinary tract infection were reported in 9 , 15 and 12 % of patients on placebo , empagliflozin 10 and 25 mg , and events consistent with genital infection were reported in 2 , 8 and 5 % , respectively . Conclusions Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo BACKGROUND Diabetes is a leading cause of chronic kidney disease ( CKD ) worldwide . Optimum glycaemic control in patients with type 2 diabetes is important to minimise the risk of microvascular and macrovascular complications and to slow the progression of CKD . We assessed the efficacy and safety of empagliflozin as an add-on treatment in patients with type 2 diabetes and CKD . METHODS We did a phase 3 , r and omised , double-blind , parallel-group , placebo-controlled trial at 127 centres in 15 countries . Patients with HbA1c of 7 % or greater to 10 % or less were eligible for inclusion . Patients with stage 2 CKD ( estimated glomerular filtration rate [ eGFR ] ≥60 to < 90 mL/min per 1·73 m(2 ) ; n=290 ) were r and omly assigned ( 1:1:1 ) to receive empagliflozin 10 mg or 25 mg or placebo once daily for 52 weeks . Patients with stage 3 CKD ( eGFR ≥30 to < 60 mL/min per 1·73 m(2 ) ; n=374 ) were r and omly assigned ( 1:1 ) to receive empagliflozin 25 mg or placebo for 52 weeks . R and omisation was done with a computer-generated r and om sequence and stratified by renal impairment , HbA1c , and background antidiabetes medication . Treatment assignment was masked from patients and investigators . The primary endpoint was change from baseline in HbA1c at week 24 by ANCOVA in the full analysis set . This study is registered with Clinical Trials.gov , number NCT01164501 . FINDINGS In patients with stage 2 CKD , adjusted mean treatment differences versus placebo in changes from baseline in HbA1c at week 24 were -0·52 % ( 95 % CI -0·72 to -0·32 ) for empagliflozin 10 mg and -0·68 % ( -0·88 to -0·49 ) for empagliflozin 25 mg ( both p<0·0001 ) . In patients with stage 3 CKD , adjusted mean treatment difference versus placebo in change from baseline in HbA1c at week 24 was -0·42 % ( -0·56 to -0·28 ) for empagliflozin 25 mg ( p<0·0001 ) . In patients with stage 2 CKD , adverse events were reported over 52 weeks by 83 patients ( 87 % ) on placebo ( 15 severe [ 16 % ] and 11 serious [ 12 % ] ) , 86 ( 88 % ) on empagliflozin 10 mg ( six severe [ 6 % ] and six serious [ 6 % ] ) and 78 ( 80 % ) on empagliflozin 25 mg ( eight severe [ 8 % ] and seven serious [ 7 % ] ) . In patients with stage 3 CKD , adverse events were reported over 52 weeks by 156 patients ( 83 % ) on placebo ( 15 severe [ 8 % ] and 23 serious [ 12 % ] ) and 156 ( 83 % ) on empagliflozin 25 mg ( 18 severe [ 10 % ] and 22 serious [ 12 % ] ) . INTERPRETATION In patients with type 2 diabetes and stage 2 or 3 CKD , empagliflozin reduced HbA1c and was well tolerated . However , our findings might not be applicable to the general population of patients with type 2 diabetes and renal impairment . FUNDING Boehringer Ingelheim , Eli Lilly Uric acid is a risk factor for coronary artery disease in postmenopausal women , but the association with inflammation and coronary endothelial dysfunction ( CED ) is not well defined . The aim of this study was to determine the relationship of serum uric acid ( SUA ) , inflammatory markers , and CED . In this prospect i ve cohort study , SUA , high-sensitivity C-reactive protein levels , and neutrophil count were measured in 229 postmenopausal women who underwent diagnostic catheterization , were found to have no obstructive coronary artery disease , and underwent coronary microvascular function testing , to measure coronary blood flow response to intracoronary acetylcholine . The average age was 58 years ( interquartile range , 52–66 years ) . Hypertension was present in 48 % , type 2 diabetes mellitus in 5.6 % , and hyperlipidemia in 61.8 % . CED was diagnosed in 59 % of postmenopausal women . Mean uric acid level was 4.7±1.3 mg/dL. Postmenopausal women with CED had significantly higher SUA compared with patients without CED ( 4.9±1.3 versus 4.4±1.3 mg/dL ; P=0.02 ) . There was a significant correlation between SUA and percent change in coronary blood flow to acetylcholine ( P=0.009 ) , and this correlation persisted in multivariable analysis . SUA levels were significantly associated with increased neutrophil count ( P=0.02 ) and high-sensitivity C-reactive protein levels ( P=0.006 ) among patients with CED , but not among those without CED . SUA is associated with CED in postmenopausal women and may be related to inflammation . These findings link SUA levels to early coronary atherosclerosis in postmenopausal women AIMS This study investigated the efficacy and tolerability of empagliflozin as add-on to pioglitazone ± metformin in patients with type 2 diabetes ( T2DM ) . METHODS Patients with HbA1c ≥7 and ≤10 % were r and omized and treated with once daily empagliflozin 10 mg ( n = 165 ) , empagliflozin 25 mg ( n = 168 ) or placebo ( n = 165 ) as add-on to pioglitazone ± metformin for 24 weeks . Endpoints included changes from baseline in HbA1c ( primary endpoint ) , fasting plasma glucose ( FPG ) and body weight at week 24 . RESULTS Adjusted mean ± st and ard error changes in HbA1c were -0.6 ± 0.07 % and -0.7 ± 0.07 % with empagliflozin 10 mg and 25 mg , respectively , vs. -0.1 ± 0.07 % with placebo ( both p < 0.001 ) . More patients with HbA1c ≥7 % at baseline achieved HbA1c < 7 % with empagliflozin 10 mg ( 23.8 % ) and 25 mg ( 30.0 % ) vs. placebo ( 7.7 % ) ( both p < 0.001 ) . FPG decreased with empagliflozin ( -0.94 mmol/l for 10 mg and -1.22 mmol/l for 25 mg ) and increased with placebo ( + 0.36 mmol/l ; both p < 0.001 ) . Adjusted mean ± st and ard error changes in weight were -1.62 ± 0.21 kg and -1.47 ± 0.21 kg with empagliflozin 10 mg and 25 mg , respectively , vs. + 0.34 ± 0.21 kg with placebo ( both p < 0.001 ) . Similar proportions of patients reported adverse events with empagliflozin ( 67.3 - 71.4 % ) and placebo ( 72.7 % ) . Confirmed hypoglycaemia was reported by 1.2 - 2.4 % of patients on empagliflozin and 1.8 % on placebo . CONCLUSION Empagliflozin 10 mg and 25 mg once daily for 24 weeks as add-on to pioglitazone ± metformin reduced HbA1c , FPG and weight and were well tolerated in patients with T2DM Introduction This study was design ed to determine the efficacy and tolerability of empagliflozin monotherapy in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Methods Patients with glycosylated hemoglobin ( HbA1c ) ≥7.0–≤10 % were r and omized via an interactive web response system , and treated double-blind with empagliflozin 5 , 10 , 25 , 50 mg , or placebo once daily for 12 weeks . The primary endpoint was change from baseline in HbA1c at week 12 . Other endpoints included percentage of patients with HbA1c < 7.0 % and changes from baseline in fasting plasma glucose ( FPG ) , body weight , and systolic blood pressure ( SBP ) at week 12 . Results A total of 547 patients were r and omized and treated with empagliflozin 5 mg ( n = 110 ) , 10 mg ( n = 109 ) , 25 mg ( n = 109 ) , 50 mg ( n = 110 ) , or placebo ( n = 109 ) for 12 weeks . Adjusted mean [ 95 % confidence interval ( CI ) ] differences vs. placebo in changes from baseline in HbA1c were −0.72 % ( −0.87 , −0.57 ) with empagliflozin 5 mg , −0.70 % ( −0.85 , −0.55 ) with 10 mg , −0.95 % ( −1.10 , −0.80 ) with 25 mg , and −0.91 ( −1.06 , −0.76 ) with 50 mg ( all p < 0.001 ) . More patients with HbA1c ≥7.0 % at baseline reached HbA1c < 7.0 % with empagliflozin ( 19–33 % ) than placebo ( 3 % ) . Compared with placebo , empagliflozin reduced FPG , body weight ( p < 0.001 for all doses for both endpoints ) and SBP ( p = 0.001 , p = 0.014 and p = 0.003 for empagliflozin 10 , 25 , and 50 mg , respectively ) . Adverse events were reported by 42 % of patients receiving placebo and 33–38 % of patients receiving empagliflozin . There were few reports of confirmed hypoglycemic adverse events or events consistent with urinary tract infection or genital infection in any treatment group . Conclusions Empagliflozin monotherapy for 12 weeks in Japanese patients with T2DM reduced HbA1c , FPG , body weight and SBP , and was well tolerated Aims : To determine the effects of empagliflozin on adiposity indices among patients with type 2 diabetes mellitus . Methods : Changes in weight , waist circumference , estimated total body fat , index of central obesity and visceral adiposity index were assessed using analysis of covariance and testing of treatment by strata for age , sex and baseline waist circumference in patients with type 2 diabetes mellitus r and omized to blinded treatment with empagliflozin versus placebo in clinical trials of 12 weeks ( cohort 1 ) or 24 weeks ( cohort 2 ) duration . Results : This study comprised 3300 patients ( cohort 1 , N = 823 ; cohort 2 , N = 2477 ) . Empagliflozin reduced weight , waist circumference and adiposity indices versus placebo in both cohorts . Adjusted mean ( 95 % confidence interval ) change from baseline in empagliflozin versus placebo was −1.7 kg ( −2.1 to −1.4 kg ) and −1.9 kg ( −2.1 to −1.7 kg ) for body weight ( p < 0.001 ) ; −1.3 cm ( −1.8 to −0.7 cm ) and −1.3 cm ( −1.7 to −1.0 cm ) for waist circumference ( p < 0.001 ) ; −0.2 % ( −0.7 % to 0.3 % ; p = 0.45 ) and −0.3 % ( −0.7 % to 0.0 % ; p = 0.08 ) for estimated total body fat ; −0.007 ( −0.011 to −0.004 ) and −0.008 ( −0.010 to −0.006 ) for index of central obesity ( p < 0.001 ) ; and −0.3 ( −0.5 to 0.0 ; p = 0.07 ) and −0.4 ( −0.7 to −0.1 ; p = 0.003 ) for visceral adiposity index in cohorts 1 and 2 , respectively . Adipose reductions were seen across most age , sex and waist circumference subgroups . Conclusion : Empagliflozin significantly reduced weight and adiposity indices with the potential to improve cardiometabolic risk among patients with type 2 diabetes mellitus AIMS To provide model-based clinical development decision support including dose selection guidance for empagliflozin , an orally administered sodium glucose cotransporter 2 inhibitor , through developed exposure-response ( E-R ) models for efficacy and tolerability in patients with type 2 diabetes mellitus ( T2DM ) . METHODS Five r and omized , placebo-controlled , multiple oral dose studies of empagliflozin in patients with T2DM ( n = 974 ; 1 - 100 mg once daily , duration ≤12 weeks ) were used to develop E-R models for efficacy ( glycosylated haemoglobin [ HbA1c ] , fasting plasma glucose [ FPG ] and urinary glucose excretion ) . Two studies ( n = 748 , 12 weeks ) were used to evaluate tolerability E-R. RESULTS The efficacy model predicted maximal decreases in FPG and HbA1c of 16 % and 0.6 % , respectively , assuming a baseline FPG concentration of 8 mm ( 144 mg dl(-1 ) ) and 10 - 25 mg every day empagliflozin targeted 80 - 90 % of these maximums . Increases in exposure had no effect on incidence rates of hypoglycaemia ( n = 4 ) , urinary tract infection ( n = 17 ) or genital/vulvovaginal-related ( n = 16 ) events , although low prevalence rates may have precluded more accurate evaluation . CONCLUSIONS E-R analyses indicated that 10 and 25 mg once daily empagliflozin doses achieved near maximal glucose lowering efficacy Canagliflozin is a sodium glucose co‐transporter 2 inhibitor in development for treatment of type 2 diabetes mellitus ( T2DM ) . This study evaluated the efficacy and safety of canagliflozin in subjects with T2DM and stage 3 chronic kidney disease [ CKD ; estimated glomerular filtration rate ( eGFR ) ≥30 and < 50 ml/min/1.73 m2 ] In patients with diabetes , glycemic improvement by sodium-glucose cotransporter-2 inhibition depends on the kidney 's ability to filter glucose . Dapagliflozin , a sodium-glucose cotransporter-2 inhibitor , reduces hyperglycemia in patients with diabetes and normal or mildly impaired renal function . In this r and omized , double-blind , placebo-controlled study we assessed daily treatment with dapagliflozin in 252 patients with inadequately controlled type 2 diabetes and moderate renal impairment . The primary endpoint , the mean change in HbA1c , was not statistically different from placebo after 24 weeks ( −0.41 % and −0.44 % for 5- and 10-mg doses , respectively , and −0.32 % for placebo ) . The mean weight change from baseline was −1.54 and −1.89 kg for the 5- and 10-mg doses , respectively , and + 0.21 kg for placebo . The mean systolic and diastolic blood pressure decreased in the dapagliflozin groups compared to placebo . Through 104 weeks , 13 patients receiving dapagliflozin and no patients receiving placebo experienced bone fracture . At 1 week , the mean serum creatinine increased with dapagliflozin 5 mg ( + 0.13 mg/dl ) and 10 mg ( + 0.18 mg/dl ) and did not change further after 104 weeks . Mean serum electrolytes did not change in any group , and there were fewer episodes of hyperkalemia with dapagliflozin than placebo . Thus , in patients with moderate renal impairment , dapagliflozin did not improve glycemic control , but reduced weight and blood pressure Sodium – glucose cotransporter 2 ( SGLT2 ) inhibitors are a newly approved class of glucose-lowering medications with a novel mechanism of action . These agents increase glycosuria , which leads to improved glucose control . They also produce an osmotic diuresis that , in part , contributes to blood pressure reduction and calorie loss secondary to glycosuria leading to weight loss ( 1,2 ) . A recent review of SGLT2 inhibitors focuses on the blood pressure – lowering effects of the two approved glucose-lowering agents , dapagliflozin and canagliflozin ( 3 ) . While not approved as antihypertensive agents , they may potentially aid in lowering blood pressure in patients with diabetes . A review of studies in both hypertensive and normotensive patients with type 2 diabetes demonstrates a 4–10 mmHg reduction of systolic blood pressure ( 3 ) . In this issue of Diabetes Care , Tikkanen et al. ( 4 ) investigate the effectiveness and safety of the newest agent in this class , empagliflozin , on blood pressure using 24-h ambulatory blood pressure monitoring . This study r and omized over 800 subjects with type 2 diabetes , mean age of 60 years , and good kidney function ( i.e. , a mean estimated glomerular filtration rate [ eGFR ] of 84 mL/min/1.73 m2 ) . These subjects either were normotensive ( < 140/90 mmHg ) or had stage 1 hypertension ( ≥140/90 < 160/99 mmHg ) . They were r and omized to either empagliflozin 10 mg daily , empagliflozin 25 mg BACKGROUND In the EMPA-REG OUTCOME ® trial , empagliflozin added to st and ard of care reduced the risk of 3-point major adverse cardiovascular ( CV ) events ( 3-point MACE : composite of CV death , non-fatal myocardial infa rct ion , or non-fatal stroke ) by 14 % , CV death by 38 % , hospitalization for heart failure by 35 % , and all-cause mortality by 32 % in patients with type 2 diabetes ( T2DM ) and established CV disease . We investigated the effects of empagliflozin in patients of Asian race . Methods and Results : Patients were r and omized to receive empagliflozin 10 mg , empagliflozin 25 mg , or placebo . Of 7,020 patients treated , 1,517 ( 21.6 % ) were of Asian race . The reduction in 3-point MACE in Asian patients was consistent with the overall population : 3-point MACE occurred in 79/1,006 patients ( 7.9 % ) in the pooled empagliflozin group vs. 58/511 patients ( 11.4 % ) in the placebo group ( hazard ratio : 0.68 [ 95 % confidence interval : 0.48 - 0.95 ] , P-value for treatment by race interaction ( Asian , White , Black/African-American ) : 0.0872 ) . The effects of empagliflozin on the components of MACE , all-cause mortality , and heart failure outcomes in Asian patients were consistent with the overall population ( P-values for interaction by race > 0.05 ) . The adverse event profile of empagliflozin in Asian patients was similar to the overall trial population . CONCLUSIONS Reductions in the risk of CV outcomes and mortality with empagliflozin in Asian patients with T2DM and established CV disease were consistent with the overall trial population AIMS To evaluate the effects of the sodium glucose cotransporter 2 ( SGLT2 ) inhibitor empagliflozin added to metformin for 12 weeks in patients with type 2 diabetes . METHODS This dose-ranging , double-blind , placebo-controlled trial r and omized 495 participants with type 2 diabetes inadequately controlled on metformin [ haemoglobin A1c ( HbA1c ) > 7 to ≤10 % ] to receive 1 , 5 , 10 , 25 , or 50 mg empagliflozin once daily ( QD ) , or placebo , or open-label sitagliptin ( 100 mg QD ) , added to metformin for 12 weeks . The primary endpoint was change in HbA1c from baseline to week 12 ( empagliflozin groups versus placebo ) . RESULTS Reductions in HbA1c of -0.09 to -0.56 % were observed with empagliflozin after 12 weeks , versus an increase of 0.15 % with placebo ( baseline : 7.8 - 8.1 % ) . Compared with placebo , empagliflozin doses from 5 to 50 mg result ed in reductions in fasting plasma glucose ( -2 to -28 mg/dl vs. 5 mg/dl with placebo ; p < 0.0001 ) and body weight ( -2.3 to -2.9 kg vs. -1.2 kg ; p < 0.01 ) . Frequency of adverse events was generally similar with empagliflozin ( 29.6 - 48.6 % ) , placebo ( 36.6 % ) and sitagliptin ( 35.2 % ) . Hypoglycaemia rates were very low and balanced among groups . Most frequent adverse events with empagliflozin were urinary tract infections ( 4.0 % vs. 2.8 % with placebo ) and pollakiuria ( 2.5 % vs. 1.4 % with placebo ) . Genital infections were reported only with empagliflozin ( 4.0 % ) . CONCLUSIONS Once daily empagliflozin as add-on therapy to metformin was well tolerated except for increased genital infections and result ed in reductions in HbA1c , fasting plasma glucose and body weight in patients with type 2 diabetes inadequately controlled on metformin monotherapy AIMS Empagliflozin is a selective sodium glucose cotransporter 2 ( SGLT2 ) inhibitor that inhibits renal glucose reabsorption and is being investigated for the treatment of type 2 diabetes mellitus ( T2DM ) . METHODS In this open-label study , the effect of renal impairment on the pharmacokinetics , pharmacodynamics and safety of a 50 mg dose of empagliflozin was investigated in 40 subjects , grouped according to estimated glomerular filtration rate ( eGFR ) . RESULTS Maximum empagliflozin plasma concentrations were similar in subjects with normal renal function and renal impairment . Area under the empagliflozin concentration-time curve ( AUC0 -∞ ) values increased by approximately 18 , 20 , 66 and 48 % in subjects with mild , moderate , severe renal impairment and renal failure/end stage renal disease ( ESRD ) , respectively , in comparison to healthy subjects . This was attributed to decreased renal clearance ( CLR ) . Urinary glucose excretion ( UGE ) decreased with increasing renal impairment and correlated with decreased eGFR and CLR . Empagliflozin was well tolerated , with no increase in adverse events associated with renal impairment . CONCLUSIONS Renal insufficiency result ed in decreased CLR of empagliflozin , moderately increased systemic exposure and decreased UGE . A single 50 mg dose of empagliflozin was well tolerated in subjects with normal renal function and any degree of renal impairment . The pharmacokinetic results of this study indicate that no dose adjustment of empagliflozin is required in patients with renal impairment OBJECTIVE Insulin resistance is associated with mitochondrial dysfunction and decreased ATP synthesis . Treatment of individuals with type 2 diabetes mellitus ( T2DM ) with sodium – glucose transporter 2 inhibitors ( SGLT2i ) improves insulin sensitivity . However , recent reports have demonstrated development of ketoacidosis in subjects with T2DM treated with SGLT2i . The current study examined the effect of improved insulin sensitivity with dapagliflozin on 1 ) mitochondrial ATP synthesis and 2 ) substrate oxidation rates and ketone production . RESEARCH DESIGN AND METHODS The study r and omized 18 individuals with T2DM to dapagliflozin ( n = 9 ) or placebo ( n = 9 ) . Before and after 2 weeks , subjects received an insulin clamp with tritiated glucose , indirect calorimetry , and muscle biopsies . RESULTS Dapagliflozin reduced fasting plasma glucose ( 167 ± 13 to 128 ± 6 mg/dL ) and increased insulin-stimulated glucose disposal by 36 % ( P < 0.01 ) . Glucose oxidation decreased ( 1.06 to 0.80 mg/kg ⋅ min , P < 0.05 ) , whereas nonoxidative glucose disposal ( glycogen synthesis ) increased ( 2.74 to 4.74 mg/kg ⋅ min , P = 0.03 ) . Dapagliflozin decreased basal glucose oxidation and increased lipid oxidation and plasma ketone concentration ( 0.05 to 0.19 mmol/L , P < 0.01 ) in association with an increase in fasting plasma glucagon ( 77 ± 8 to 94 ± 13 , P < 0.01 ) . Dapagliflozin reduced the ATP synthesis rate , which correlated with an increase in plasma ketone concentration . CONCLUSIONS Dapagliflozin improved insulin sensitivity and caused a shift from glucose to lipid oxidation , which , together with an increase in glucagon-to-insulin ratio , provide the metabolic basis for increased ketone production In the EMPA-REG OUTCOME trial , therapy with the sodium/glucose co-transporter ( SGLT ) 2 inhibitor empagliflozin over just 2.6 years was associated with a 14 % reduction in the risk of major cardiovascular events , driven by a marked and unexpected reduction in cardiovascular mortality ( 38 % ) in patients with type 2 diabetes and established cardiovascular disease [ 1 ] . The drug also reduced the incidence of heart failure hospitalisation ( HFH ) by 35 % . The magnitude of these benefits and their rapid emergence after only a few months from r and omisation make it unlikely that the modest benefits on HbA1c ( −0.4 % compared with placebo ) , body weight ( −2 kg ) and systolic/diastolic blood pressure ( 4/2 mmHg ) were responsible [ 1 ] . Moreover , the divergence in the HRs for non-fatal myocardial infa rct ion ( HR 0.87 [ 95 % CI 0.70 , 1.09 ] ) vs non-fatal stroke ( HR 1.24 [ 0.92 , 1.67 ] ) makes it unlikely that the benefits of empagliflozin involved classical effects on atherosclerosis . Accordingly , additional mechanisms and mediators need to be considered to better underst and why empagliflozin had such important benefits in this trial [ 2–5 ] . Based on their mode of action , SGLT2 inhibitors induce natriuresis and osmotic diuresis , associated with significant reductions in systolic and diastolic blood pressure . The result ant decrease in plasma volume and both cardiac preload and afterload may have obvious benefits for the heart , particularly in patients with impaired left ventricular function . However , it should be noted that only 10 % of trial participants had recognised heart failure at baseline [ 6 ] . In addition , in clinical trials , anti-hypertensive agents and , specifically , diuretics , have not been demonstrated to have such strong protective cardiovascular effects , particularly on cardiovascular death and HFH . Only a recent trial involving eplerenone in patients with heart failure ( but not necessarily diabetes ) has demonstrated a similarly rapid improvement in heart failure outcomes [ 7 ] . Thus , it is conceivable that empagliflozin ’s diuretic activity contributed at least partially to the improved cardiovascular outcomes observed in EMPA-REG OUTCOME via an improvement in haemodynamics , decreasing myocardial stretch and the risk of developing potentially lethal arrhythmias . Yet , the results of this trial remain surprising , leading investigators to propose other mediators . As noted , additional factors that might explain the cardiovascular protective effects of empagliflozin include weight * Roberto Vettor In the EMPA-REG BP trial , empagliflozin 10 mg and 25 mg once daily reduced glycohemoglobin , blood pressure ( BP ) , and weight versus placebo in patients with type 2 diabetes mellitus and hypertension . Patients received placebo ( n=271 ) , empagliflozin 10 mg ( n=276 ) , or empagliflozin 25 mg ( n=276 ) for 12 weeks ( n = full analysis set ) . This present analysis investigated changes from baseline to week 12 in mean 24-hour systolic BP ( SBP ) and diastolic BP ( DBP ) in patients receiving 0 , 1 , or ≥2 antihypertensive medications and patients receiving/not receiving diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers . Compared with placebo , empagliflozin 10 mg and 25 mg reduced mean 24-hour SBP/DBP in patients receiving 0 ( 10 mg : −3.89/−2.58 mm Hg ; 25 mg : −3.77/−2.45 mm Hg ) , 1 ( 10 mg : −4.74/−1.97 mm Hg ; 25 mg : −4.27/−1.81 mm Hg ) , or ≥2 ( 10 mg : −2.36/−0.68 mm Hg ; 25 mg : −4.17/−1.54 mm Hg ) antihypertensives . The effect of empagliflozin was not significantly different between subgroups by number of antihypertensives for changes in SBP ( interaction P value 0.448 ) or DBP ( interaction P value 0.498 ) . Empagliflozin reduced 24-hour mean SBP/DBP irrespective of diuretic or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use , with no significant difference between subgroups by use/no use of diuretics ( interaction P values 0.380 [ systolic ] ; 0.240 [ diastolic ] ) or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers ( interaction P values 0.900 [ systolic ] ; 0.359 [ diastolic ] ) . In conclusion , in patients with type 2 diabetes mellitus and hypertension , empagliflozin for 12 weeks reduced SBP and DBP versus placebo , irrespective of the number of antihypertensives and use of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers . Clinical Trial Registration —URL : https:// clinical trials.gov . Unique identifier : NCT01370005 BACKGROUND Sodium-glucose cotransporter 2 ( SGLT2 ) inhibitors improve glycaemia in patients with type 2 diabetes by enhancing urinary glucose excretion . We compared the efficacy and safety of canagliflozin , an SGLT2 inhibitor , with glimepiride in patients with type 2 diabetes inadequately controlled with metformin . METHODS We undertook this 52 week , r and omised , double-blind , active-controlled , phase 3 non-inferiority trial at 157 centres in 19 countries between Aug 28 , 2009 , and Dec 21 , 2011 . Patients aged 18 - 80 years with type 2 diabetes and glycated haemoglobin A1c ( HbA1c ) of 7·0 - 9·5 % on stable metformin were r and omly assigned ( 1:1:1 ) by computer-generated r and om sequence via an interactive voice or web response system to receive canagliflozin 100 mg or 300 mg , or glimepiride ( up-titrated to 6 mg or 8 mg per day ) orally once daily . Patients , study investigators , and local sponsor personnel were masked to treatment . The primary endpoint was change in HbA1c from baseline to week 52 , with a non-inferiority margin of 0·3 % for the comparison of each canagliflozin dose with glimepiride . If non-inferiority was shown , we assessed superiority on the basis of an upper bound of the 95 % CI for the difference of each canagliflozin dose versus glimepiride of less than 0·0 % . Analysis was done in a modified intention-to-treat population , including all r and omised patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT00968812 . FINDINGS 1450 of 1452 r and omised patients received at least one dose of glimepiride ( n=482 ) , canagliflozin 100 mg ( n=483 ) , or canagliflozin 300 mg ( n=485 ) . For lowering of HbA1c at 52 weeks , canagliflozin 100 mg was non-inferior to glimepiride ( least-squares mean difference -0·01 % [ 95 % CI -0·11 to 0·09 ] ) , and canagliflozin 300 mg was superior to glimepiride ( -0·12 % [ -0·22 to -0·02 ] ) . 39 ( 8 % ) patients had serious adverse events in the glimepiride group versus 24 ( 5 % ) in the canagliflozin 100 mg group and 26 ( 5 % ) in the 300 mg group . In the canagliflozin 100 mg and 300 mg groups versus the glimepiride group , we recorded a greater number of genital mycotic infections ( women : 26 [ 11 % ] and 34 [ 14 % ] vs five [ 2 % ] ; men : 17 [ 7 % ] and 20 [ 8 % ] vs three [ 1 % ] ) , urinary tract infections ( 31 [ 6 % ] for both canagliflozin doses vs 22 [ 5 % ] ) , and osmotic diuresis-related events ( pollakiuria : 12 [ 3 % ] for both doses vs one [ < 1 % ] ; polyuria : four [ < 1 % ] for both doses vs two [ < 1 % ] ) . INTERPRETATION Canagliflozin provides greater HbA1c reduction than does glimepiride , and is well tolerated in patients with type 2 diabetes receiving metformin . These findings support the use of canagliflozin as a viable treatment option for patients who do not achieve sufficient glycaemic control with metformin therapy . FUNDING Janssen Research & Development , LLC Abstract Aims We previously reported that in the EMPA-REG OUTCOME ® trial , empagliflozin added to st and ard of care reduced the risk of 3-point major adverse cardiovascular events , cardiovascular and all-cause death , and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk . We have now further investigated heart failure outcomes in all patients and in subgroups , including patients with or without baseline heart failure . Methods and results Patients were r and omized to receive empagliflozin 10 mg , empagliflozin 25 mg , or placebo . Seven thous and and twenty patients were treated ; 706 ( 10.1 % ) had heart failure at baseline . Heart failure hospitalization or cardiovascular death occurred in a significantly lower percentage of patients treated with empagliflozin [ 265/4687 patients ( 5.7 % ) ] than with placebo [ 198/2333 patients ( 8.5 % ) ] [ hazard ratio , HR : 0.66 ( 95 % confidence interval : 0.55–0.79 ) ; P < 0.001 ] , corresponding to a number needed to treat to prevent one heart failure hospitalization or cardiovascular death of 35 over 3 years . Consistent effects of empagliflozin were observed across subgroups defined by baseline characteristics , including patients with vs. without heart failure , and across categories of medications to treat diabetes and /or heart failure . Empagliflozin improved other heart failure outcomes , including hospitalization for or death from heart failure [ 2.8 vs. 4.5 % ; HR : 0.61 ( 0.47–0.79 ) ; P < 0.001 ] and was associated with a reduction in all-cause hospitalization [ 36.8 vs. 39.6 % ; HR : 0.89 ( 0.82–0.96 ) ; P = 0.003 ] . Serious adverse events and adverse events leading to discontinuation were reported by a higher proportion of patients with vs. without heart failure at baseline in both treatment groups , but were no more common with empagliflozin than with placebo . Conclusion In patients with type 2 diabetes and high cardiovascular risk , empagliflozin reduced heart failure hospitalization and cardiovascular death , with a consistent benefit in patients with and without baseline heart failure |
12,483 | 31,191,964 | Conclusion For individuals with rotator cuff calcific tendinopathy , low- quality evidence suggests that ultrasound-guided lavage is more effective than shockwave therapy or a corticosteroid injection alone . | Background Rotator cuff calcific tendinopathy is characterised by the deposition of hydroxyapatite crystals in one of the rotator cuff tendons and can be managed by ultrasound-guided lavage .
However , evidence regarding the efficacy of ultrasound-guided lavage for rotator cuff calcific tendinopathy remains inconclusive .
The aim of this systematic review and meta- analysis is to up date the available evidence on the efficacy of ultrasound-guided lavage in adults with rotator cuff calcific tendinopathy . | We carried out a prospect i ve , r and omised controlled trial on two groups of 40 patients with painful calcific tendonitis and a mean age of 48.4 years ( 32.5 to 67.3 ) . All were to undergo arthroscopic removal of the calcific deposit within six months after r and omisation . The 40 patients in group I received ultrasound-guided needling followed by high-energy shock-wave therapy and the 40 in group II had shock-wave therapy alone . In both groups one treatment consisting of 2500 impulses of shock waves with an energy flux density of 0.36 mJ/mm(2 ) was applied . The clinical and radiological outcome was assessed using the 100-point Constant shoulder scoring system and st and ardised radiographs . The mean follow-up was 4.1 months and no patient was lost to follow-up . Both groups had significant improvement in their Constant shoulder score . Radiographs showed disappearance of the calcific deposit in 60.0 % of the shoulders in group I and in 32.5 % of group II ( p < 0.05 ) . Significantly better clinical and radiological results were obtained in group I than in group II . Arthroscopic removal of the deposit was avoided in 32 patients of group I and in 22 of group II . No severe side-effects were recorded . Ultrasound-guided needling in combination with high-energy shock-wave therapy is more effective than shock-wave therapy alone in patients with symptomatic calcific tendonitis , giving significantly higher rates of elimination of the calcium deposits , better clinical results and reduction in the need for surgery BACKGROUND Knowledge about Minimal Important Differences ( MIDs ) is essential for the interpretation of continuous outcomes , especially patient-reported outcome measures ( PROMS ) . OBJECTIVE The aim of this study was to estimate the MID for the Western Ontario Rotator Cuff Index ( WORC : score 0 ( best ) to 2100 ( worst disability ) ) in adults with shoulder pain associated with partial-thickness rotator cuff tears , ' symptomatic PTTs ' , undergoing conservative treatment with physiotherapy . DESIGN A prospect ively- design ed anchor-based MID analysis using data from a prospect i ve prognostic study with a three-month follow-up conducted within an outpatient care setting in Germany . METHODS The MID was estimated using data from 64 adults with atraumatic symptomatic PTTs who underwent three months of conservative treatment with physiotherapy . The anchor was a seven-point Global Perceived Change ( GPC ) scale . RESULTS Based on a definition of the MID being the threshold of " being ( at least slightly ) improved " with a probability nearest to 0.90 ( i.e. 9 of 10 patients achieving the MID ) , the MID for the WORC was estimated as -300 for ' improved ' shoulder-related disability in 9 out of 10 patients ( 95 % CI 8 out of 10 patients to everyone ) undergoing three months of exercise-based physiotherapy for symptomatic PTTs . CONCLUSIONS This is the first published MID estimate for the WORC in adults with symptomatic PTTs of the rotator cuff undergoing typical treatment comprising conservative treatment with physiotherapy . The conceptual framework for interpretation facilitates its use in similar clinical context Background : Barbotage ( needling and lavage ) is often applied in the treatment of calcific tendinitis of the rotator cuff ( RCCT ) . In a previously published r and omized controlled trial , we reported superior clinical and radiological 1-year outcomes for barbotage combined with a corticosteroid injection in the subacromial bursa ( SAIC ) compared with an isolated SAIC . There are no trials with a midterm or long-term follow-up of barbotage available . Purpose : To compare the 5-year results of 2 regularly applied treatments of RCCT : ultrasound (US)–guided barbotage combined with a SAIC ( group 1 ) versus an isolated US-guided SAIC ( group 2 ) . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Patients were r and omly assigned to group 1 or 2 and evaluated before and after treatment at regular time points until 12 months and also at 5 years using the Constant score ( CS ) , the Western Ontario Rotator Cuff Index ( WORC ) , and the Disabilities of the Arm , Shoulder and H and ( DASH ) . The calcification location and size and Gärtner classification were assessed on radiographs . The rotator cuff condition was evaluated with US . Results were analyzed using t tests , linear regression , and a mixed model for repeated measures . Results : Forty-eight patients were included ( mean age , 52.0 ± 7.3 years ; 25 [ 52 % ] female ) with a mean baseline CS of 68.7 ± 11.9 . After a mean follow-up of 5.1 ± 0.5 years , the mean CS was 90 ( 95 % CI , 83.0 - 95.9 ) in group 1 versus 87 ( 95 % CI , 80.5 - 93.5 ) in group 2 ( P = .58 ) . The mean improvement in the CS in group 1 was 18 ( 95 % CI , 12.3 - 23.0 ) versus 21 ( 95 % CI , 16.2 - 26.2 ) in group 2 ( P = .32 ) . There was total resorption in 62 % of group 1 and 73 % of group 2 ( P = .45 ) . The US evaluation of the rotator cuff condition showed no significant differences between the groups . With the mixed model for repeated measures , taking into account the baseline CS and Gärtner classification , the mean treatment effect for barbotage was 6 ( 95 % CI , –8.9 to 21.5 ) , but without statistical significance . Follow-up scores were significantly associated with baseline scores and the duration of follow-up . Results for the DASH and WORC were similar . There were no significant complications , but 4 patients in group 1 and 16 in group 2 underwent additional treatment during the follow-up period ( P < .001 ) . Conclusion : No more significant differences were found in the clinical and radiological outcomes between barbotage combined with a SAIC versus an isolated SAIC after 5 years of follow-up . Registration : NTR2282 ( Dutch Trial Registry ) OBJECTIVE Calcific tendonitis of rotator cuff is observed on plain radiographs in 10 % of adults , but remains asymptomatic in half these cases . We looked for differences on ultrasound ( US ) and power Doppler findings between symptomatic and asymptomatic cases of shoulder calcific tendonitis . METHODS US was performed in 62 patients ( 81 shoulders ) with symptomatic ( n=57 ) or asymptomatic ( n=24 ) calcific tendonitis . Calcific plaque morphology , power Doppler signaling , and widening of the subacromial-subdeltoid bursa ( SSB ) were recorded . US-guided steroid injection into the SSB ( n=21 ) or needle puncture of calcific deposits ( n=29 ) was performed at the end of US evaluation in 50 of the 57 patients , and a question naire was sent to each patient after 11+/-6 months . RESULTS Larger ( p=0.0015 ) and fragmented ( p=0.01 ) calcifications were associated with pain . A power Doppler signal and a widening of the SSB was identified in 21 and 17 of the 57 symptomatic calcification respectively , but in none of the cases of asymptomatic calcification ( p<0,005 ) . At least one of these signs was present in 31 of the 57 ( 54 % ) symptomatic shoulders ( p<0.001 ) . Long-term outcome was favourable for 60 % of our patients after steroid injection . The presence of a SSB widening before bursal steroid injection was associated with an improvement of the symptoms ( p=0.06 ) . CONCLUSION Positive power Doppler signal within the calcific deposit and SSB widening are US features strongly associated with pain . Moreover , larger calcifications are also more symptomatic . According to these results , US can help physicians to confirm that calcification is responsible for shoulder pain BACKGROUND Extracorporeal shockwave treatment ( ESWT ) and ultrasound-guided percutaneous lavage ( UGPL ) are two effective ways of treating rotator cuff calcific tendinopathy ( RCCT ) . AIM The aim of the present study was to compare the effectiveness of these techniques in the treatment of RCCT . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Patients treated in our sports medicine and rehabilitation center ( Centro Médico Deyre , Madrid . Spain ) between January 2007 and December 2013 . METHODS This r and omized study compares the results achieved with these techniques over one year following their use to treat the above condition . Eighty patients received ESWT and 121 received UGPL . A visual analogue scale was used to measure pain , and ultrasound to determine the extent of calcification , at 3 , 6 , and 12 months after treatment . RESULTS Pain and the amount of calcification were significantly reduced by both techniques at 3 , 6 and 12 months ( P<0.001 for each ) , but significantly more so by UGPL ( P<0.001 ) . CONCLUSIONS Both techniques are valid for the treatment of RCCT , although UGPL is associated with a greater reduction of calcification and greater reduction in pain . CLINICAL REHABILITATION IMPACT The results obtained applying UGPL , the low cost and the lack of complications should therefore make the treatment of choice in centers that are appropriately equipped and staffed HYPOTHESIS Ultrasound (US)-guided needling with subacromial corticosteroid injection is more effective than extracorporeal shock wave therapy ( ESWT ) for function restoration and pain relief in patients with calcific tendinitis of the shoulder . METHODS Fifty-four patients diagnosed with unilateral painful calcific tendinitis were r and omly allocated to a US needling or ESWT group . The US needling group underwent US-guided needling and received a subacromial corticosteroid injection . The ESWT group received ESWT 3 times a week . All patients were prospect ively evaluated ; American Shoulder and Elbow Surgeons , Simple Shoulder Test , and visual analog scale for pain scores were recorded before the procedure and at 6 weeks , 12 weeks , 6 months , 12 months , and the last follow-up . The size and morphology of the deposits were evaluated by radiography . RESULTS The average follow-up period was 23.0 months . At last follow-up , the mean size of the deposits was significantly different between the 2 groups ( P = .001 ) ; it decreased to 0.5 mm from 14.8 mm in the US needling group and to 5.6 mm from 11.0 mm in the ESWT group . There were also significant improvements in clinical outcomes in both groups after treatment ( P < .05 ) . At 1-year follow-up , the US needling group had significantly better scores than the ESWT group with regard to the American Shoulder and Elbow Surgeons assessment ( 90.3 and 74.6 , respectively ; P = .001 ) , Simple Shoulder Test ( 83.3 and 70.8 , respectively ; P = .015 ) , and visual analog scale for pain ( 1.4 and 3.3 , respectively ; P = .003).The initial calcium deposit sizes and clinical outcomes were weakly correlated in both groups ( P > .05 ) . CONCLUSION Both treatment modalities for calcific tendinitis improved clinical outcomes and eliminated calcium deposits . US-guided needling treatment , however , was more effective in function restoration and pain relief in the short term BACKGROUND The minimal clinical ly important difference ( MCID ) is increasingly used to evaluate treatment effectiveness . The MCID for the Constant score has not been previously reported . MATERIAL S AND METHODS A prospect ively collected cohort of 802 consecutive shoulders with arthroscopically treated partial- or full-thickness rotator cuff tears was analyzed . The Constant score was measured preoperatively and at 3 months and 1 year postoperatively . At follow-up visits , the patients were asked a simple 2-stage question : Is the shoulder better or worse after the operation compared with the preoperative state ? This single 2-level question was used as an indicator of patient satisfaction and as an anchor to calculate the MCID for the Constant score . RESULTS At 1 year , 781 ( 97.4 % ) patients ( 474 men , 307 women ) were available for follow-up . The preoperative Constant score was 53.1 ( SD 17.2 ) in all patients , 56.2 ( SD 17.4 ) in male patients , and 48.2 ( SD 15.6 ) in female patients . Postoperatively at 3 months , the scores were 61.7 ( SD 16.4 ) in all patients , 65.1 ( SD 16.1 ) in male patients , and 56.8 ( SD 15.5 ) in female patients . At 1 year , the scores were 75.9 ( SD 15.2 ) in all patients , 79.0 ( SD 14.9 ) in male patients , and 71.0 ( SD 14.3 ) in female patients . At 3 months postoperatively , 92.2 % of male patients and 87.2 % of female patients were satisfied with the outcome ( P = .027 ) ; at 1 year , the satisfaction was 93.2 % and 89.5 % , respectively ( P = .067 ) . Five different statistical approaches yielded 5 different MCID estimates ( range , 2 - 16 ) . The 3-month mean change estimate of MCID was 10.4 points . CONCLUSION Our study demonstrates an MCID estimate of 10.4 points as the threshold for the Constant score in patients with rotator cuff tear . LEVEL OF EVIDENCE Basic science study , validation of outcomes instruments/classification systems OBJECTIVE The purpose of this study was to determine the minimal important change ( MIC ) of improvement in the Constant-Murley score in patients with long-st and ing subacromial pain and in subgroups of patients with subacromial pain with and without rotator cuff ruptures . METHOD The MIC was estimated by the anchor-based MIC distribution method , which integrates an anchor- and distribution-based approach : the optimal cutoff point of the receiver operating characteristic curve ( MICROC ) and the 95 % limit cutoff point ( MIC95 % limit ) . The study population consisted of 93 patients included in a r and omized clinical trial evaluating the effect of a specific exercise strategy . RESULTS The MICROC was found at a mean change of 17 points in the Constant-Murley score , which corresponds to a sensitivity of 91 % and a specificity of 79 % . The MIC95 % limit was found at a mean change of 24 points . In the subgroup analysis , the MICROC was found at a mean change of 19 points and the MIC95 % limit at 18 points in patients with an intact rotator cuff . In patients with rotator cuff ruptures , the MICROC was found at a mean change of 15 points and the MIC95 % limit at 30 points . CONCLUSION The Constant-Murley score is able to detect the MIC in individual patients with long-st and ing subacromial pain when the rotator cuff is intact . The estimated MIC values could be used as an indication for relevant changes in the Constant-Murley score in clinical practice and guide the clinician in how to interpret the results of specific treatments Background : Calcific tendinitis of the rotator cuff ( RCCT ) is frequently diagnosed in patients with shoulder pain , but there is no consensus on its treatment . Purpose : To compare 2 regularly applied RCCT treatments : ultrasound (US)–guided needling and lavage ( barbotage ) combined with a US-guided corticosteroid injection in the subacromial bursa ( subacromial bursa injection [ SAI ] ) ( group 1 ) versus an isolated SAI ( group 2 ) . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Patients were r and omly assigned to the 2 groups . Shoulder function was assessed before treatment and at regular follow-up intervals ( 6 weeks and 3 , 6 , and 12 months ) using the Constant shoulder score ( CS , primary outcome ) , the Western Ontario Rotator Cuff Index ( WORC ) , and the Disabilities of the Arm , Shoulder and H and question naire ( DASH ) . Additionally , calcification location , size , and Gärtner classification were assessed on radiographs . Results were analyzed using the t test , linear regression , and a mixed model for repeated measures . Results : This study included 48 patients ( 25 female , 52.1 % ; mean age , 52.0 ± 7.3 years ; 23 patients in group 1 ) with a mean baseline CS of 68.7 ± 11.9 . No patients were lost to follow-up . Four patients in group 1 and 11 in group 2 ( P = .06 ) had an additional barbotage procedure or surgery during the follow-up period because of persisting symptoms and no resorption . At 1-year follow-up , the mean CS in group 1 was 86.0 ( 95 % CI , 80.3 - 91.6 ) versus 73.9 ( 95 % CI , 67.7 - 80.1 ) in group 2 ( P = .005 ) . The mean calcification size decreased by 11.6 ± 6.4 mm in group 1 and 5.1 ± 5.7 mm in group 2 ( P = .001 ) . There was total resorption in 13 patients in group 1 and 6 patients in group 2 ( P = .07 ) . With regression analyses , correcting for baseline CS and Gärtner type , the mean treatment effect was 20.5 points ( P = .05 ) in favor of barbotage . Follow-up scores were significantly influenced by baseline scores . Results for the DASH and WORC were similar . Conclusion : On average , there was improvement at 1-year follow-up in both treatment groups , but clinical and radiographic results were significantly better in the barbotage group |
12,484 | 31,473,609 | Overall , the performance of these diabetes-specific stroke prediction models was not satisfactory . | OBJECTIVE Stroke is a major cause of disability and death worldwide .
People with diabetes are at a twofold to fivefold increased risk for stroke compared with people without diabetes .
This study systematic ally review s the literature on available stroke prediction models specifically developed or vali date d in patients with diabetes and assesses their predictive performance through meta- analysis . | Background To assess whether the Multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus ( RAMP-DM ) led to improvements in biomedical outcomes , observed cardiovascular events and predicted cardiovascular risks after 12-month intervention in the primary care setting . Methods A r and om sample of 1,248 people with diabetes enrolled to RAMP-DM for at least 12 months was selected and 1,248 people with diabetes under the usual primary care were matched by age , sex , and HbA1c level at baseline as the usual care group . Biomedical and cardiovascular outcomes were measured at baseline and at 12-month after the enrollment . Difference-in-differences approach was employed to measure the effect of RAMP-DM on the changes in biomedical outcomes , proportion of subjects reaching treatment targets , observed and predicted cardiovascular risks . Results Compared to the usual care group , RAMP-DM group had lower cardiovascular events incidence ( 1.21 % vs 2.89 % , P = 0.003 ) , and net decrease in HbA1c ( −0.20 % , P < 0.01 ) , SBP ( −3.62 mmHg , P < 0.01 ) and 10-year cardiovascular disease ( CVD ) risks ( total CVD risk , −2.06 % , P < 0.01 ; coronary heart disease ( CHD ) risk , −1.43 % , P < 0.01 ; stroke risk , −0.71 % , P < 0.01 ) . The RAMP-DM subjects witnessed significant rises in the proportion of reaching treatment targets of HbA1c , and SBP/DBP . After adjusting for confounding variables , the significance remained for HbA1c , predicted CHD and stroke risks . Conclusions The RAMP-DM result ed in greater improvements in HbA1c and reduction in observed and predicted cardiovascular risks at 12 months follow-up , which indicated a risk-stratification multidisciplinary intervention was an effective strategy for managing Chinese people with diabetes in the primary care setting .Trial registry Clinical Trials.gov , OBJECTIVE To evaluate the accuracy of the UK Prospect i ve Diabetes Study Outcomes Model ( UKPDS-OM ) in predicting clinical outcomes during the UKPDS posttrial monitoring ( PTM ) period . RESEARCH DESIGN AND METHODS At trial end in 1997 , the 4,031 surviving UKPDS patients , of the 5,102 originally enrolled in the study , returned to their usual care providers , with no attempts made to maintain them in their r and omized therapy groups . PTM risk factor data were collected for 5 years and clinical outcome data for 10 years . The UKPDS-OM was used firstly to forecast likely progression of HbA1c , systolic blood pressure , total-to-HDL cholesterol ratio , and smoking status and secondly to estimate the likely first occurrence of seven major diabetes-related complications or death from any cause . Model predictions were compared against observed PTM data for risk factor time paths and survival probabilities for major diabetes complications . RESULTS UKPDS-OM – forecasted risk factor time paths were similar to those observed for HbA1c ( up to 3 years ) and total-to-HDL cholesterol ratio but underestimated for systolic blood pressure and smoking status . Predicted 10-year event probabilities were similar to those observed for blindness , ischemic heart disease , myocardial infa rct ion , and renal failure but were higher for heart failure and death from any cause and lower for stroke and amputation . CONCLUSIONS The UKPDS-OM has good predictive accuracy for two of four risk factor time paths and for 10-year clinical outcome probabilities with the exception of stroke , amputation , heart failure , and death from any cause . An up date d version of the model incorporating PTM data is being developed Summary A total of 6695 diabetic men and women , aged 35 to 54 years , from 14 centres and representing 13 national groups , participated in a vascular disease prevalence survey . A r and om sample was drawn after stratification of each centre 's diabetic base population by sex , duration of diabetes and age . A common agreed protocol , st and ardized examination procedures , and central ized laboratory methods were used in the investigation . Within the age range examined there was considerable variation between centres in a number of variables , including degree of obesity ( measured as Body Mass Index ( BMI ) ) , proportion treated with insulin and proportion of cigarette smokers . The latter also showed considerable sex differences within centres . Subjects with age at onset below 25 years were notably few in Hong Kong , Tokyo and Oklahoma . There was also considerable variation in the apparent prevalence of both large- and small-vessel ( macrovascular and microvascular ) disease between centres . In pooled data , measures of large-vessel disease were significantly and independently associated with age , blood pressure and BMI in both sexes , and with diabetes duration and plasma cholesterol in men only . Within-centre analyses showed blood pressure to be the most consistently associated variable in both sexes . In pooled data , small-vessel disease of the eye was significantly and independently associated with diabetes duration , blood pressure , BMI and type of treatment in both sexes . In within-centre analyses , diabetes duration was the most consistently associated variable , followed by blood pressure . Proteinuria as an index of small-vessel disease of the kidney was , in pooled data , significantly and independently correlated with diabetes duration , blood pressure and plasma cholesterol in both sexes . In within-centre analyses , blood pressure was the most consistently associated variable , with diabetes duration and plasma cholesterol equal second -significant in 12 of the 28 centre/sex groups . Heterogeneity of large-vessel disease prevalence in diabetic subjects is confirmed by this study , and the possibility of heterogeneity in small-vessel disease prevalence and severity is suggested Introduction . The objective of this study was to create a tool that accurately predicts the risk of morbidity and mortality in patients with type 2 diabetes according to an oral hypoglycemic agent . Material s and Methods . The model was based on a cohort of 33,067 patients with type 2 diabetes who were prescribed a single oral hypoglycemic agent at the Clevel and Clinic between 1998 and 2006 . Competing risk regression models were created for coronary heart disease ( CHD ) , heart failure , and stroke , while a Cox regression model was created for mortality . Propensity scores were used to account for possible treatment bias . A prediction tool was created and internally vali date d using tenfold cross-validation . The results were compared to a Framingham model and a model based on the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) for CHD and stroke , respectively . Results and Discussion . Median follow-up for the mortality outcome was 769 days . The numbers of patients experiencing events were as follows : CHD ( 3062 ) , heart failure ( 1408 ) , stroke ( 1451 ) , and mortality ( 3661 ) . The prediction tools demonstrated the following concordance indices ( c-statistics ) for the specific outcomes : CHD ( 0.730 ) , heart failure ( 0.753 ) , stroke ( 0.688 ) , and mortality ( 0.719 ) . The prediction tool was superior to the Framingham model at predicting CHD and was at least as accurate as the UKPDS model at predicting stroke . Conclusions . We created an accurate tool for predicting the risk of stroke , coronary heart disease , heart failure , and death in patients with type 2 diabetes . The calculator is available online at http://rcalc.ccf.org under the heading “ Type 2 Diabetes ” and entitled , “ Predicting 5-Year Morbidity and Mortality . ” This may be a valuable tool to aid the clinician ’s choice of an oral hypoglycemic , to better inform patients , and to motivate dialogue between physician and patient OBJECTIVE We sought to vali date Risk Equations for Complications of Type 2 Diabetes ( RECODe ) among diverse population s. RESEARCH DESIGN AND METHODS We compared risk predictions from RECODe equations and from two alternative risk models ( UK Prospect i ve Diabetes Study Outcomes Model 2 [ UKPDS OM2 ] and American College of Cardiology/American Heart Association Pooled Cohort Equations ) to observed outcomes in two studies : the Multi-Ethnic Study of Atherosclerosis ( MESA , n = 1,555 adults with type 2 diabetes , median follow-up 9.1 years ) and the Jackson Heart Study ( JHS , n = 1,746 adults with type 2 diabetes , median follow-up 8.0 years ) . Outcomes included nephropathy by multiple measures ( microalbuminuria , macroalbuminuria , renal failure , end-stage renal disease , and reduction in glomerular filtration rate ) , moderate to severe diabetic retinopathy by Airlie House classification , fatal or nonfatal myocardial infa rct ion , fatal or nonfatal stroke , congestive heart failure , and all-cause mortality . RESULTS RECODe equations for microvascular and cardiovascular outcomes had C-statistics for discrimination ranging from 0.71 to 0.85 in MESA and 0.64 to 0.91 in JHS for alternative outcomes . Calibration slopes in MESA ranged from 0.62 for a composite nephropathy outcome , 0.83–1.04 for individual nephropathy outcomes , 1.07 for retinopathy , 1.00–1.05 for cardiovascular outcomes , and 1.03 for all-cause mortality . Slopes in JHS ranged from 0.47 for retinopathy , 0.97–1.16 for nephropathy , 0.72–1.05 for cardiovascular outcomes , and 1.01 for all-cause mortality . The alternative models had C-statistics 0.50–0.72 and calibration slopes 0.07–0.60 . CONCLUSIONS RECODe equations improved risk estimation for diverse patients with type 2 diabetes , as compared with two commonly used alternatives Objective To develop and vali date version two of the QRISK cardiovascular disease risk algorithm ( QRISK2 ) to provide accurate estimates of cardiovascular risk in patients from different ethnic groups in Engl and and Wales and to compare its performance with the modified version of Framingham score recommended by the National Institute for Health and Clinical Excellence ( NICE ) . Design Prospect i ve open cohort study with routinely collected data from general practice , 1 January 1993 to 31 March 2008 . Setting 531 practice s in Engl and and Wales contributing to the national Q RESEARCH data base . Participants 2.3 million patients aged 35 - 74 ( over 16 million person years ) with 140 000 cardiovascular events . Overall population ( derivation and validation cohorts ) comprised 2.22 million people who were white or whose ethnic group was not recorded , 22 013 south Asian , 11 595 black African , 10 402 black Caribbean , and 19 792 from Chinese or other Asian or other ethnic groups . Main outcome measures First ( incident ) diagnosis of cardiovascular disease ( coronary heart disease , stroke , and transient ischaemic attack ) recorded in general practice records or linked Office for National Statistics death certificates . Risk factors included self assigned ethnicity , age , sex , smoking status , systolic blood pressure , ratio of total serum cholesterol : high density lipoprotein cholesterol , body mass index , family history of coronary heart disease in first degree relative under 60 years , Townsend deprivation score , treated hypertension , type 2 diabetes , renal disease , atrial fibrillation , and rheumatoid arthritis . Results The validation statistics indicated that QRISK2 had improved discrimination and calibration compared with the modified Framingham score . The QRISK2 algorithm explained 43 % of the variation in women and 38 % in men compared with 39 % and 35 % , respectively , by the modified Framingham score . Of the 112 156 patients classified as high risk ( that is , ≥20 % risk over 10 years ) by the modified Framingham score , 46 094 ( 41.1 % ) would be reclassified at low risk with QRISK2 . The 10 year observed risk among these reclassified patients was 16.6 % ( 95 % confidence interval 16.1 % to 17.0%)—that is , below the 20 % treatment threshold . Of the 78 024 patients classified at high risk on QRISK2 , 11 962 ( 15.3 % ) would be reclassified at low risk by the modified Framingham score . The 10 year observed risk among these patients was 23.3 % ( 22.2 % to 24.4%)—that is , above the 20 % threshold . In the validation cohort , the annual incidence rate of cardiovascular events among those with a QRISK2 score of ≥20 % was 30.6 per 1000 person years ( 29.8 to 31.5 ) for women and 32.5 per 1000 person years ( 31.9 to 33.1 ) for men . The corresponding figures for the modified Framingham equation were 25.7 per 1000 person years ( 25.0 to 26.3 ) for women and 26.4 ( 26.0 to 26.8 ) for men ) . At the 20 % threshold , the population identified by QRISK2 was at higher risk of a CV event than the population identified by the Framingham score . Conclusions Incorporating ethnicity , deprivation , and other clinical conditions into the QRISK2 algorithm for risk of cardiovascular disease improves the accuracy of identification of those at high risk in a nationally representative population . At the 20 % threshold , QRISK2 is likely to be a more efficient and equitable tool for treatment decisions for the primary prevention of cardiovascular disease . As the validation was performed in a similar population to the population from which the algorithm was derived , it potentially has a “ home advantage . ” Further validation in other population s is therefore advised AIMS A risk scoring system for predicting ischemic stroke incidence may identify type 2 diabetes patients at high risk for ischemic stroke who can benefit from preventive intervention programs . Such a risk scoring system can serve as a benchmark to test novel putative risk factors . METHODS The study adopted a retrospective cohort , including 28,124 Chinese patients with type 2 diabetes aged 30 - 84 years during 2001 - 2004 . Participants were r and omly assigned to the derivation and validation sets at a 2:1 ratio . Cox 's proportional hazard regression model was used to identify risk factors of ischemic stroke incidence in the derivation set . And then the steps proposed by the Framingham Heart Study for establishing an ischemic stroke prediction model with a scoring system was used . RESULTS Among 9374 patients in the validation set , 1076 subjects ( 11.48 % ) developed ischemic stroke with a mean follow up period of 8.0 years . We identified the following risk factors : age , gender , smoking habit , duration of type 2 diabetes , blood pressure , HbA1c level , total cholesterol to high-density lipoprotein ratio , creatinine , fasting plasma glucose variation ( FPG-CV ) , arterial embolism and thrombosis , diabetes retinopathy , hypoglycemia , anti-diabetes medication use , and cardiovascular medication . The area under receiver operating characteristic curve of the 3-year , 5-year , and 8-year ischemic stroke incidence risks were 0.72 , 0.71 , and 0.68 for the validation set , respectively . CONCLUSIONS This proposed ischemic stroke incidence risk prediction model is the first model established for Chinese patients with type 2 diabetes recruited from nationwide clinical setting BACKGROUND In view of substantial mis-estimation of risks of diabetes complications using existing equations , we sought to develop up date d Risk Equations for Complications Of type 2 Diabetes ( RECODe ) . METHODS To develop and vali date these risk equations , we used data from the Action to Control Cardiovascular Risk in Diabetes study ( ACCORD , n=9635 ; 2001 - 09 ) and vali date d the equations for microvascular events using data from the Diabetes Prevention Program Outcomes Study ( DPPOS , n=1018 ; 1996 - 2001 ) , and for cardiovascular events using data from the Action for Health in Diabetes ( Look AHEAD , n=4760 ; 2001 - 12 ) . Microvascular outcomes were nephropathy , retinopathy , and neuropathy . Cardiovascular outcomes were myocardial infa rct ion , stroke , congestive heart failure , and cardiovascular mortality . We also included all-cause mortality as an outcome . We used a cross-validating machine learning method to select predictor variables from demographic characteristics , clinical variables , comorbidities , medications , and biomarkers into Cox proportional hazards models for each outcome . The new equations were compared to older risk equations by assessing model discrimination , calibration , and the net reclassification index . FINDINGS All equations had moderate internal and external discrimination ( C-statistics 0·55 - 0·84 internally , 0·57 - 0·79 externally ) and high internal and external calibration ( slopes 0·71 - 1·31 between observed and estimated risk ) . Our equations had better discrimination and calibration than the UK Prospect i ve Diabetes Study Outcomes Model 2 ( for microvascular and cardiovascular outcomes , C-statistics 0·54 - 0·62 , slopes 0·06 - 1·12 ) and the American College of Cardiology/American Heart Association Pooled Cohort Equations ( for fatal or non-fatal myocardial infa rct ion or stroke , C-statistics 0·61 - 0·66 , slopes 0·30 - 0·39 ) . INTERPRETATION RECODe might improve estimation of risk of complications for patients with type 2 diabetes . FUNDING National Institute for Diabetes and Digestive and Kidney Disease , National Heart , Lung and Blood Institute , and National Institute on Minority Health and Health Disparities , National Institutes of Health , and US Department of Veterans Affairs OBJECTIVE To develop and vali date a risk engine that calculates the risks of macro- and microvascular complications in type 2 diabetes . RESEARCH DESIGN AND METHODS We analyzed pooled data from two clinical trials on 1,748 Japanese type 2 diabetic patients without diabetes complications other than mild diabetic retinopathy with a median follow-up of 7.2 years . End points were coronary heart disease ( CHD ) , stroke , noncardiovascular mortality , overt nephropathy defined by persistent proteinuria , and progression of retinopathy . We fit a multistate Cox regression model to derive an algorithm for prediction . The predictive accuracy of the calculated 5-year risks was cross-vali date d. RESULTS Sex , age , HbA1c , years after diagnosis , BMI , systolic blood pressure , non-HDL cholesterol , albumin-to-creatinine ratio , atrial fibrillation , current smoker , and leisure-time physical activity were risk factors for macro- and microvascular complications and were incorporated into the risk engine . The observed-to-predicted ( O/P ) ratios for each event were between 0.93 and 1.08 , and Hosmer-Lemeshow tests showed no significant deviations between observed and predicted events . In contrast , the UK Prospect i ve Diabetes Study ( UKPDS ) risk engine overestimated CHD risk ( O/P ratios : 0.30 for CHD and 0.72 for stroke ) . C statistics in our Japanese patients were high for CHD , noncardiovascular mortality , and overt nephropathy ( 0.725 , 0.696 , and 0.767 ) but moderate for stroke and progression of retinopathy ( 0.636 and 0.614 ) . By combining macro- and microvascular risks , the classification of low- and high-risk patients was improved by a net reclassification improvement of 5.7 % ( P = 0.02 ) . CONCLUSIONS The risk engine accurately predicts macro- and microvascular complications and would provide helpful information in risk classification and health economic simulations Aims /hypothesisThe aim of this study was to develop a simulation model for Type 2 diabetes that can be used to estimate the likely occurrence of major diabetes-related complications over a lifetime , in order to calculate health economic outcomes such as quality -adjusted life expectancy . Methods Equations for forecasting the occurrence of seven diabetes-related complications and death were estimated using data on 3642 patients from the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) . After examining the internal validity , the UKPDS Outcomes Model was used to simulate the mean difference in expected quality -adjusted life years between the UKPDS regimens of intensive and conventional blood glucose control . Results The model ’s forecasts fell within the 95 % confidence interval for the occurrence of observed events during the UKPDS follow-up period . When the model was used to simulate event history over patients ’ lifetimes , those treated with a regimen of conventional glucose control could expect 16.35 undiscounted quality -adjusted life years , and those receiving treatment with intensive glucose control could expect 16.62 quality -adjusted life years , a difference of 0.27 ( 95 % CI : −0.48 to 1.03 ) . Conclusions /interpretationsThe UKPDS Outcomes Model is able to simulate event histories that closely match observed outcomes in the UKPDS and that can be extrapolated over patients ’ lifetimes . Its validity in estimating outcomes in other groups of patients , however , remains to be evaluated . The model allows simulation of a range of long-term outcomes , which should assist in informing future economic evaluations of interventions in Type 2 diabetes A definitive model for predicting absolute risk of coronary heart disease ( CHD ) in male and female people with Type II diabetes is not yet available . This paper provides an equation for estimating the risk of new CHD events in people with Type II diabetes , based on data from 4540 U.K. Prospect i ve Diabetes Study male and female patients . Unlike previously published risk equations , the model is diabetes-specific and incorporates glycaemia , systolic blood pressure and lipid levels as risk factors , in addition to age , sex , ethnic group , smoking status and time since diagnosis of diabetes . All variables included in the final model were statistically significant ( P<0.001 , except smoking for which P=0.0013 ) in likelihood ratio testing . This model provides the estimates of CHD risk required by current guidelines for the primary prevention of CHD in Type II diabetes Background : Chronic kidney disease ( CKD ) is an independent risk factor for cardiovascular disease ( CVD ) . However , the association between CKD and CVD risk in patients with type 2 diabetes mellitus ( T2DM ) in China has not yet been well investigated . This study aim ed to determine the association of CKD with the risks of coronary heart disease ( CHD ) and stroke in a Chinese population with T2DM . Methods : A total of 1401 in patients with T2DM at the Second Affiliated Hospital of Zhejiang University School of Medicine between April 2008 and November 2013 were included in this study . The CKD-Epidemiology Collaboration equation for Asians was used to classify CKD . The UK Prospect i ve Diabetes Study risk engine was used to estimate the risks of CHD and stroke . Results : CHD risk was significantly increased with CKD stage ( 20.1 % , 24.8 % , and 34.3 % in T2DM patients with no CKD , CKD Stage 1–2 , and Stage 3–5 , respectively ; P < 0.001 for all ) . The stroke risk was also increased with CKD stage ( 8.6 % , 12.7 % , and 25.4 % in T2DM patients with no CKD , CKD Stage 1–2 , and Stage 3–5 , respectively ; P < 0.001 for all ) . Compared with no-CKD group , the odds ratios ( ORs ) for high CHD risk were 1.7 ( P < 0.001 ) in the CKD Stage 1–2 group and 3.5 ( P < 0.001 ) in the CKD Stage 3–5 group . The corresponding ORs for high stroke risk were 1.9 ( P < 0.001 ) and 8.2 ( P < 0.001 ) , respectively . Conclusion : In patients with T2DM , advanced CKD stage was associated with the increased risks of CHD and stroke Background We evaluated the ability of 23 novel biomarkers representing several pathophysiological pathways to improve the prediction of cardiovascular event ( CVE ) risk in patients with type 2 diabetes mellitus beyond traditional risk factors . Methods and Results We used data from 1002 patients with type 2 diabetes mellitus from the Second Manifestations of ARTertial disease ( SMART ) study and 288 patients from the European Prospect i ve Investigation into Cancer and Nutrition‐NL ( EPIC‐NL ) . The associations of 23 biomarkers ( adiponectin , C‐reactive protein , epidermal‐type fatty acid binding protein , heart‐type fatty acid binding protein , basic fibroblast growth factor , soluble FMS‐like tyrosine kinase‐1 , soluble intercellular adhesion molecule‐1 and ‐3 , matrix metalloproteinase [MMP]‐1 , MMP‐3 , MMP‐9 , N‐terminal prohormone of B‐type natriuretic peptide , osteopontin , osteonectin , osteocalcin , placental growth factor , serum amyloid A , E‐selectin , P‐selectin , tissue inhibitor of MMP‐1 , thrombomodulin , soluble vascular cell adhesion molecule‐1 , and vascular endothelial growth factor ) with CVE risk were evaluated by using Cox proportional hazards analysis adjusting for traditional risk factors . The incremental predictive performance was assessed with use of the c‐statistic and net reclassification index ( NRI ; continuous and based on 10‐year risk strata 0–10 % , 10–20 % , 20–30 % , > 30 % ) . A multimarker model was constructed comprising those biomarkers that improved predictive performance in both cohorts . N‐terminal prohormone of B‐type natriuretic peptide , osteopontin , and MMP‐3 were the only biomarkers significantly associated with an increased risk of CVE and improved predictive performance in both cohorts . In SMART , the combination of these biomarkers increased the c‐statistic with 0.03 ( 95 % CI 0.01–0.05 ) , and the continuous NRI was 0.37 ( 95 % CI 0.21–0.52 ) . In EPIC‐NL , the multimarker model increased the c‐statistic with 0.03 ( 95 % CI 0.00–0.03 ) , and the continuous NRI was 0.44 ( 95 % CI 0.23–0.66 ) . Based on risk strata , the NRI was 0.12 ( 95 % CI 0.03–0.21 ) in SMART and 0.07 ( 95 % CI −0.04–0.17 ) in EPIC‐NL . Conclusions Of the 23 evaluated biomarkers from different pathophysiological pathways , N‐terminal prohormone of B‐type natriuretic peptide , osteopontin , MMP‐3 , and their combination improved CVE risk prediction in 2 separate cohorts of patients with type 2 diabetes mellitus beyond traditional risk factors . However , the number of patients reclassified to a different risk stratum was limited A representation and interpretation of the area under a receiver operating characteristic ( ROC ) curve obtained by the " rating " method , or by mathematical predictions based on patient characteristics , is presented . It is shown that in such a setting the area represents the probability that a r and omly chosen diseased subject is ( correctly ) rated or ranked with greater suspicion than a r and omly chosen non-diseased subject . Moreover , this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic . These two relationships are exploited to ( a ) provide rapid closed-form expressions for the approximate magnitude of the sampling variability , i.e. , st and ard error that one uses to accompany the area under a smoothed ROC curve , ( b ) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area , and ( c ) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques OBJECTIVE —Risk prediction models obtained in sample s from the general population do not perform well in type 2 diabetic patients . Recently , 5-year risk estimates were proposed as being more accurate than 10-year risk estimates . This study presents a diabetes-specific equation for estimation of the absolute 5-year risk of first incident fatal/nonfatal cardiovascular disease ( CVD ) in type 2 diabetic patients with use of A1C and clinical characteristics . RESEARCH DESIGN AND METHODS —The study was based on 11,646 female and male patients , aged 18–70 years , from the Swedish National Diabetes Register with 1,482 first incident CVD events based on 58,342 person-years with mean follow-up of 5.64 years . RESULTS —This risk equation incorporates A1C , as in the UK Prospect i ve Diabetes Study risk engine , and several clinical characteristics : onset age of diabetes , diabetes duration , sex , BMI , smoking , systolic blood pressure , and antihypertensive and lipid-reducing drugs . All predictors included were associated with the outcome ( P < 0.0001 , except for BMI P = 0.0016 ) with Cox regression analysis . Calibration was excellent when assessed by comparing observed and predicted risk . Discrimination was sufficient , with a receiver operator curve statistic of 0.70 . Mean 5-year risk of CVD in all patients was 12.0 ± 7.5 % , whereas 54 % of the patients had a 5-year risk ≥10 % . CONCLUSIONS —This more simplified risk equation enables 5-year risk prediction of CVD based on easily available nonlaboratory predictors in clinical practice and A1C and was elaborated in a large observational study obtained from the normal patient population aged up to 70 years BACKGROUND AND PURPOSE The risk of stroke is known to be markedly elevated in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) , but the information on risk factors predicting stroke events in middle-aged NIDDM patients is limited . Therefore , we evaluated the significance of different cardiovascular risk factors with respect to the incidence of stroke in middle-aged NIDDM patients . METHODS Levels of cardiovascular risk factors were determined at baseline in 1059 NIDDM patients ( 581 men , 478 women ) and 1373 nondiabetic control subjects ( 638 men , 735 women ) , aged from 45 to 64 years , in eastern and western Finl and . These patients were followed up for 7 years with respect to stroke events . RESULTS Altogether , 34 NIDDM patients ( 13 men , 21 women ) and 5 nondiabetic subjects ( 4 men , 1 woman ) died from stroke , and 125 NIDDM patients ( 61 men , 64 women ) and 30 ( 18 men , 12 women ) nondiabetic subjects had a fatal or nonfatal stroke . The risk of stroke in NIDDM men was about threefold and in NIDDM women fivefold higher than that in corresponding nondiabetic subjects . Previous history of stroke increased the risk of a new stroke event by threefold . Patients with hyperglycemia ( plasma glucose > 13.4 mmol/L ) and high hemoglobin A1 ( > 10.7 % ) had about a twofold higher risk of stroke than patients with better glycemic control . Low levels of high-density lipoprotein cholesterol ( < 0.90 mmol/L ) , high levels of total triglyceride ( > 2.30 mmol/L ) , and the presence of hypertension were associated with a twofold increase in the risk of stroke mortality or morbidity . CONCLUSIONS Our prospect i ve population -based study gives evidence that previous history of stroke , hypertension , hyperglycemia , and dyslipidemia are strong predictors of stroke in middle-aged patients with NIDDM OBJECTIVE To assess the performance of the Framingham and United Kingdom Prospect i ve Diabetes Study ( UKPDS ) cardiovascular risk equations in Australian patients with type 2 diabetes who were initially free of cardiovascular disease ( CVD ) . DESIGN AND SETTING The Fremantle Diabetes Study ( FDS ) , a community-based longitudinal observational study ; data for the period 1993 - 2006 were used . PATIENTS Of the 815 FDS participants with type 2 diabetes who were initially CVD-free , 791 ( 97 % ) were eligible for assessment using the UKPDS equations , and 697 ( 86 % ) using the Framingham equation . MAIN OUTCOME MEASURES CVD endpoints during 5 years of follow-up . For the UKPDS equations , these were fatal myocardial infa rct ion ( MI ) or sudden death ( fatal coronary heart disease [ CHD ] ) ; hospitalisation for/with or death from MI or sudden death ( all CHD ) ; fatal stroke ; and all stroke . For the Framingham equation , they were all MI , sudden death or angina pectoris ( CHD ) . RESULTS During follow-up to first CVD event , death or 5 years , there were 38 MIs ( 11 fatal ) and 23 strokes ( 13 fatal ) in the UKPDS-assessable cohort of FDS participants . The UKPDS risk equations for all CHD , fatal CHD , and all stroke overestimated the number of events by 6.5 , 2.8 and 1.8 times , respectively . The risk equation for fatal stroke underestimated the number of events by 38 % . The UKPDS CHD risk equations showed modest discrimination and poor calibration , while the stroke risk equations showed good discrimination and calibration . The Framingham equation predicted 28 % fewer CHD events than occurred ( 93 v 130 ) , and discrimination and calibration were poor . CONCLUSIONS While the UKPDS stroke risk equations performed relatively well , the UKPDS and Framingham CHD risk equations are not suitable for predicting risk in Australians with type 2 diabetes Background and Purpose — People with type 2 diabetes are at elevated risk of stroke compared with those without diabetes . Relative risks have been examined in earlier work , but there is no readily available method for predicting the absolute risk of stroke in a diabetic individual . We developed mathematical models to estimate the risk of a first stroke using data from 4549 newly diagnosed type 2 diabetic patients enrolled in the UK Prospect i ve Diabetes Study . Methods — During 30 700 person-years of follow-up , 188 first strokes ( 52 fatal ) occurred . Model fitting was carried out by maximum likelihood estimation using the Newton-Raphson method . Diagnostic plots were used to compare survival probabilities calculated by the model with those calculated using nonparametric methods . Results — Variables included in the final model were duration of diabetes , age , sex , smoking , systolic blood pressure , total cholesterol to high-density lipoprotein cholesterol ratio and presence of atrial fibrillation . Not included in the model were body mass index , hemoglobin A1c , ethnicity , and ex-smoking status . The use of the model is illustrated with a hypothetical study power calculation . Conclusions — This model forecasts the absolute risk of a first stroke in people with type 2 diabetes using variables readily available in routine clinical practice Objective Predicting the risk of future events is an essential part of health economic simulation models . In pursuit of this goal , the current study aims to predict the risk of developing first and second acute myocardial infa rct ion , heart failure , non-acute ischaemic heart disease , and stroke after diagnosis in patients with type 2 diabetes , using data from the Swedish National Diabetes Register . Material and Methods Register data on 29,034 patients with type 2 diabetes were analysed over five years of follow up ( baseline 2003 ) . To develop and vali date the risk equations , the sample was r and omly divided into training ( 75 % ) and test ( 25 % ) sub sample s. The Weibull proportional hazard model was used to estimate the coefficients of the risk equations , and these were vali date d in both the training and the test sample s. Results In total , 4,547 first and 2,418 second events were observed during the five years of follow up . Experiencing a first event substantially elevated the risk of subsequent events . There were heterogeneities in the effects of covariates within as well as between events ; for example , while for females the hazard ratio of having a first acute myocardial infa rct ion was 0.79 ( 0.70–0.90 ) , the hazard ratio of a second was 1.21 ( 0.98–1.48 ) . The hazards of second events decreased as the time since first events elapsed . The equations showed adequate calibration and discrimination ( C statistics range : 0.70–0.84 in test sample s ) . Conclusion The accuracy of health economic simulation models of type 2 diabetes can be improved by ensuring that they account for the heterogeneous effects of covariates on the risk of first and second cardiovascular events . Thus it is important to extend such models by including risk equations for second cardiovascular events OBJECTIVE We have previously observed that genetic profiles determined by the combination of five functionally significant single nucleotide polymorphisms ( SNPs ) ( rs1800795 , rs5498 , rs5361 , rs1024611 , and rs679620 ) of genes encoding prototypical inflammatory molecules are associated with history of ischemic stroke . Here we tested the ability of this multigenic model to predict stroke risk in a large population -based prospect i ve cohort of subjects with type 2 diabetes . RESEARCH DESIGN AND METHODS This study was conducted using a prospect i ve cohort of individuals with type 2 diabetes participating in the Go-DARTS ( Genetics of Diabetes Audit and Research in Tayside Scotl and ) study , which includes genetic and clinical information of patients with diabetes within the Tayside region of Scotl and , U.K. The above-mentioned inflammatory SNPs were investigated in 2,182 Go-DARTS participants . We created an inflammatory risk score ( IRS ) , ranging from 0 to 5 , according to the number of “ at-risk ” genotypes concomitantly carried by a given individual . The primary outcome was the occurrence of fatal or nonfatal stroke of any kind . Mean follow-up time was 6.2 ± 1.1 years . RESULTS The incidence of stroke increased according to the IRS . The IRS was significantly and independently associated with increased stroke risk after adjustment for other conventional risk factors ( hazard ratio 1.34 [ 95 % CI 1.1–1.7 ] ; P = 0.009 ) . The highest hazard ratio for stroke was found in subjects concomitantly carrying > 3 proinflammatory variations and in subjects without previous cardiovascular diseases . CONCLUSIONS This large prospect i ve cohort study provides evidence that SNPs of genes encoding prototypical inflammatory molecules may be used to create multigenic models that predict stroke risk in subjects with type 2 diabetes Aims /hypothesisThe United Kingdom Prospect i ve Diabetes Study ( UKPDS ) Outcomes Model can be used to estimate the lifetime occurrence of major diabetes-related complications in order to calculate health economic outcomes . The aim of the study was to assess the performance of the model by comparing the predicted and observed mortality and the incidence of macrovascular complications in an Italian population -based cohort with type 2 diabetes . Methods We used data from the Casale Monferrato Survey , a cohort enrolled in 1988 and surveyed in 1991 ( n = 1,967 ) to assess the prevalence of cardiovascular risk factors . In 2000 , a new survey included all the members of the original cohort who were still alive ( n = 860 ) , and in addition all individuals identified with a new diagnosis of type 2 diabetes since 1993 ( n = 2,389 ) . We compared the mortality predicted by the model for the 1991 survey over the subsequent 17-year period with the observed risk . The following outcomes were analysed in the 2000 survey : myocardial infa rct ion ( MI ) , other ischaemic heart disease , stroke , congestive heart failure ( CHF ) and amputation . Results For all-cause mortality , the predictions from the model at 5 and 10 years ( 23 % and 47 % , respectively ) were identical to the observed risks . At 15 years , the risk of death was slightly overestimated ( an estimate of 67 % vs 64 % observed , 95 % CI 61 % , 66 % ) . The performance of the model was best for patients with a recent history of disease ( duration < 6 years ) . Among the complications , the predicted cumulative incidences of MI and CHF were very close to those observed . Conclusions /interpretationExternal validation is essential to assess the accuracy of simulation models . The UKPDS Outcomes Model satisfactorily predicted a set of actual incidences of mortality and complications in an Italian diabetes cohort up to a duration of approximately 12 years . The longer term performance of such models should be carefully evaluated OBJECTIVE Patients with diabetes have a higher case fatality rate in myocardial infa rct ion ( MI ) or stroke than those without diabetes : that is , MI and stroke are more often fatal if diabetes is present . We investigated whether the risk of MI or stroke being fatal in type 2 diabetes can be estimated using information available around the time diabetes is diagnosed . RESEARCH DESIGN AND METHODS Analyses were based on 674 cases of MI ( 351 fatal ) that occurred in 597 of 5,102 U.K. Prospect i ve Diabetes Study ( UKPDS ) patients for whom covariate data were available during a median follow-up of 7 years . Multivariate logistic regression was used to examine differences in risk factors , measured within 2 years of diagnosis of diabetes , between fatal and nonfatal MI . Similar analyses were performed for 234 strokes ( 48 fatal ) that occurred in 199 patients . RESULTS Patients with fatal MI had higher HbA(1c ) than those with nonfatal MI ( odds ratio 1.17 per 1 % HbA(1c ) , P = 0.014 ) . Patients with fatal stroke had higher HbA(1c ) than those with nonfatal stroke ( odds ratio 1.37 per 1 % HbA(1c ) , P = 0.007 ) . Other risk factors for MI case fatality included increased age , blood pressure , and urine albumin level . CONCLUSIONS The risk of MI or stroke being fatal in type 2 diabetes is associated with risk factors , including HbA(1c ) , measured many years before onset of MI or stroke . Equations have been added to the UKPDS Risk Engine to estimate likely case fatality rates in MI and stroke OBJECTIVE —We sought to develop stroke risk equations for Chinese patients with type 2 diabetes in Hong Kong . RESEARCH DESIGN AND METHODS —A total of 7,209 Hong Kong Chinese type 2 diabetic patients without a history of stroke at baseline were analyzed . The data were r and omly and evenly divided into the training sub sample and the test sub sample . In the training sub sample , stepwise Cox models were used to develop the risk equation . Validation of the U.K. Prospect i ve Diabetes Study ( UKPDS ) stroke risk engine and the current stroke equation was performed in the test data set . The life-table method was used to check calibration , and the area under the receiver operating characteristic curve ( aROC ) was used to check discrimination . RESULTS —A total of 372 patients developed incident stroke during a median of 5.37 years ( interquartile range 2.88–7.78 ) of follow-up . Age , A1C , spot urine albumin-to-creatinine ratio ( ACR ) , and history of coronary heart disease ( CHD ) were independent predictors . The performance of the UKPDS stroke engine was suboptimal in our cohort . The newly developed risk equation defined by these four predictors had adequate performance in the test sub sample . The predicted stroke-free probability by the current equation was within the 95 % CI of the observed probability . The aROC was 0.77 for predicting stroke within 5 years . The risk score was computed as follows : 0.0634 × age ( years ) + 0.0897 × A1C + 0.5314 × log10 ( ACR ) ( mg/mmol ) + 0.5636 × history of CHD ( 1 if yes ) . The 5-year stroke probability can be calculated by : 1 − 0.9707EXP ( Risk Score − 4.5674 ) . CONCLUSIONS —Although the risk equation performed reasonably well in Chinese type 2 diabetic patients , external validation is required in other population AIM To compare three methods of assessing 5-year absolute risk of cardiovascular disease ( CVD ) in adults with type 2 diabetes ; the Framingham CVD equation , the UK Prospect i ve Diabetes Study ( UKPDS ) coronary heart disease plus stroke equations and the New Zeal and Guidelines Group (NZGG)-modified Framingham CVD equation . METHODS Participants were 423 people with newly ( n=118 ) or previously diagnosed ( n=305 ) Type 2 diabetes mellitus aged 35 to 74 years with no past history of cardiovascular disease or nephropathy from an interviewed study population of 4049 adults . Absolute 5-year CVD risks were calculated in 5-year age b and s by gender ; Maori , Pacific , and European ethnicity ; and newly and previously diagnosed diabetes . RESULTS The mean 5-year CVD risk score was 2.9 % ( 95%CI : 2.40 - 3.42 ; p<0.0001 ) lower for the UKPDS risk engine compared to the original Framingham equation in absolute terms , and 7.6 % ( 95%CI : 7.05 - 8.08 ; p<0.0001 ) lower than the NZGG-modified Framingham equation . In general , 5-year CVD risks were highest using the NZGG-modified equation , intermediate using the original Framingham equation and lowest using the combined UKPDS coronary heart disease plus stroke equations , in all age groups by gender , ethnicity , and time of diagnosis of Type 2 diabetes . However , the 5-year CVD risks are themselves potentially low as they include treated blood pressure and lipid values . Compared to the UKPDS 15 % level of risk , the NZ Guidelines modified 15 % level of risk results in people with diabetes being recommended for CVD drug management 10 to 17 years earlier . CONCLUSIONS In general , among people with Type 2 diabetes , the Framingham equations showed higher 5-year CVD risk estimates compared to combined UKPDS coronary heart disease plus stroke equations and the NZGG-modified Framingham equation showed the highest 5-year CVD risks . In practice , people with type 2 diabetes will be managed earlier and more intensively based on their risk estimated by the current NZGG guidelines than if the UKPDS or original Framingham equations were used Aims /hypothesisThe aim of this study was to investigate the association of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) with traditional cardiovascular risk factors and incident cardiovascular events in older people with type 2 diabetes . Methods In the prospect i ve phase of the Edinburgh Type 2 Diabetes Study , 1066 men and women aged 60 to 75 years with type 2 diabetes mellitus were followed for 4 years ; 112 participants had an incident cardiovascular event . At baseline , cardiovascular risk factors , pre-existing cardiovascular disease and levels of NT-proBNP were evaluated . Results Raised plasma NT-proBNP levels were associated with these classical cardiovascular risk factors : increased duration of diabetes , use of insulin , raised BMI , reduced HDL-cholesterol , reduced renal function and use of lipid-lowering and anti-hypertensive medication ( all p < 0.05 ) . In the prospect i ve analysis , NT-proBNP was strongly associated with subsequent risk of all cardiovascular disease events ( HR per one SD increase in NT-proBNP 1.39 ; 95 % CI 1.10 , 1.75 ) , independent of cardiovascular risk factors traditionally used to predict vascular events . NT-proBNP was also independently associated with incident coronary artery disease events ( 1.48 , 95 % CI 1.10 , 1.98 ) . The addition of NT-proBNP to multivariate models improved the C-index by 0.019 for the ‘ hard ’ cardiac endpoint ( fatal and non-fatal myocardial infa rct ion ) . Conclusions /interpretationIn older people with type 2 diabetes , NT-proBNP is associated with the development of coronary and cerebrovascular events , independent of a wide range of other vascular and metabolic risk factors , and may prove a useful addition to current vascular risk scores in diabetes population OBJECTIVE Primary prevention of Coronary Heart Disease ( CHD ) in diabetic patients should be based on absolute CHD risk calculation . This study was aim ed to determine the levels of 10-year CHD risk in Caribbean type 2 diabetic patients using the diabetes specific United Kingdom Prospect i ve Diabetes Study ( UKPDS ) risk engine calculator . SUBJECTS AND METHODS Three hundred and twenty-five ( 106 males , 219 females ) type 2 diabetic patients resident in two Caribbean Isl and s of Tobago and Trinidad met the UKPDS risk engine inclusion criteria . Records of their sex , age , ethnicity , smoking habit , diabetes duration , systolic blood pressure , total cholesterol , HDL-cholesterol and glycated haemoglobin were entered into the UKPDS risk engine calculator programme and the absolute 10-year CHD and stroke risk levels were computed . The 10-year CHD and stroke risks were statistically stratified into < 15 % , 15 - 30 % and > 30 % CHD risk levels and differences between patients of African and Asian-Indian origin were compared . RESULTS In comparison with patients in Tobago , type 2 diabetic patients in Trinidad , irrespective of gender , had higher proportion of 10-year CHD risk ( 10.4 vs. 23.6 % , P<0.001 ) whereas the overall 10-year stroke risk prediction was higher in patients resident in Tobago ( 16.9 vs. 11.4 % , P<0.001 ) . Ethnicity-based analysis revealed that irrespective of gender , higher proportion of patients of Indian origin scored > 30 % of absolute 10-year CHD risk compared with patients of African descent ( 3.2 vs. 28.2 % , P<0.001 ) . CONCLUSIONS The results of the study identified diabetic patients resident in Trinidad and patients of Indian origin as the most vulnerable groups for CHD . These groups of diabetic patients should have priority in primary or secondary prevention of coronary heart disease BACKGROUND The concept of risk estimation of Coronary Heart Disease ( CHD ) is helpful for clinician to identifying high risk population s for their effective treatment . Latest studies recommended only initiating cardioprotective treatment in diabetic patients based on personalized CHD risk estimates so as to reduce undue harm from overly aggressive risk factor modification . The United Kingdom Prospect i ve Diabetes Study ( UK PDS ) Risk Engine is a widely used tool to assess the risk of Cardio Vascular diseases ( CVD ) in diabetics . The literature search so far did not reveal any study of risk assessment among Pakistani Diabetics . METHODS This descriptive study is based on the data of 470 type-2 diabetics seen in Department of Endocrinology and Metabolism , Services Institute of Medical Sciences , Lahore during 2011 . The data of these 470 patients was analyzed through UKPDS Risk Engine . CHD risk was calculated . RESULTS The 10 years risk of CHD , fatal CHD , stroke and fatal stroke was 9.4 % , 4.4 % , 1.7 % and 0.2 % respectively . CONCLUSIONS The present study show a lower risk of CVD occurring among Pakistani diabetics as compared to studies from western countries Objective Economic evaluations of new diabetes therapies rely heavily upon the UK Prospect i ve Diabetes Study ( UKPDS ) equations for prediction of cardiovascular events ; however , concerns persist regarding their relevance to current clinical practice and appropriate use in population s other than newly diagnosed patients . This study refits the UKPDS 68 event equations , using contemporary data describing low- and intermediate-risk patients . Research Design and Methods Anonymized patient data describing demographics , risk factors and incidence of cardiovascular and microvascular events were extracted from The Health Improvement Network ( THIN ) data base over the 10-year period from 1 January 2000 to 31 December 2009 . Following multiple imputation of missing values , accelerated failure-time Weibull regression equations were refitted to produce new coefficients for each risk group . Discriminatory performance was assessed and compared with both UKPDS 68 and UKPDS 82 risk equations , and the implication of coefficient choice within an economic evaluation was assessed using the Cardiff type 2 diabetes model . Results When applied to patient-level data , the three sets of coefficients ( UKPDS , THIN low-risk and intermediate-risk ) lead to fairly consistent predictions of the 5-year risk of events . Exceptions include lower predicted rates of myocardial infa rct ion and higher rates of ischaemic heart disease , congestive heart failure and end-stage renal disease with both sets of revised THIN coefficients compared with UKPDS . Over a modelled lifetime , the coefficients derived from the low-risk data predict fewer total cardiovascular events compared with UKPDS , while those from the intermediate-risk data predict a greater number . The areas under the receiver – operating characteristic curves demonstrated a marginal improvement in the discriminatory performance of the refitted equations . The incremental cost-effectiveness ratio associated with dapagliflozin versus sulphonylurea in addition to metformin changed from £ 7,708 to £ 7,519 and £ 6,906 per QALY gained , using the THIN intermediate- and low-risk coefficients , respectively . Conclusion The results suggest that while the UKPDS equations perform best in newly diagnosed patients , they may overpredict the lifetime risk in this group and underpredict it in patients with more advanced diabetes . Implementation of the revised coefficients will result in different absolute numbers of predicted diabetes-related events ; however , they are not expected to significantly affect the conclusions of economic modelling Abstract Carotid atherosclerosis ( CA ) and carotid plaque ( CP ) are highly correlated with cardiovascular disease . We aim ed to determine the prevalence of CA and CP and their relationship with 10-year risks of stroke and coronary heart disease ( CHD ) in type 2 diabetes mellitus ( T2DM ) . We studied 1584 T2DM patients aged 20 years and older . CA and CP were detected using ultrasonography . Ten-year stroke and CHD risk were determined using the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) risk engine . The prevalence of CA and CP increased gradually with age . Men had a higher prevalence of CA than women ( CA : 58.18 % vs 51.54 % , P < .01 ) . The 10-year CHD risk ( 27.9 % vs 15.4 % , P < .001 ) and stroke risk ( 15.2 % vs 5.70 % , P < .001 ) were higher in patients with CA than that of those without CA . Compared with patients without CA , the odds ratios ( ORs ) of CHD in CA and CP group were 4.47 and 10.78 for men , and 4.19 and 5.20 for women , respectively ; in the case of stroke , the OR in CA and CP group were 8.83 and 12.07 for men , and 4.35 and 4.90 for women , respectively ( P < .001 for all ) . Multivariate binary logistic regression analysis showed that CA was an independent risk factor for CHD [ OR = 2.66 , 95 % confidence interval ( 95 % CI ) , 2.05–3.46 , P < .001 ] and stroke ( OR = 3.11 , 95 % CI , 2.38–4.07 , P < .001 ) . CA and CP were prevalent in patients with T2DM and positively correlated with 10-year CHD and stroke risk . CA was an independent risk factor for 10-year CHD risk AIMS To develop a prediction equation for 10-year risk of a combined endpoint ( incident coronary heart disease , stroke , heart failure , chronic kidney disease , lower extremity hospitalizations ) in people with diabetes , using demographic and clinical information , and a panel of traditional and non-traditional biomarkers . METHODS We included in the study 654 participants in the Atherosclerosis Risk in Communities ( ARIC ) study , a prospect i ve cohort study , with diagnosed diabetes ( visit 2 ; 1990 - 1992 ) . Models included self-reported variables ( Model 1 ) , clinical measurements ( Model 2 ) , and glycated haemoglobin ( Model 3 ) . Model 4 tested the addition of 12 blood-based biomarkers . We compared models using prediction and discrimination statistics . RESULTS Successive stages of model development improved risk prediction . The C-statistics ( 95 % confidence intervals ) of models 1 , 2 , and 3 were 0.667 ( 0.64 , 0.70 ) , 0.683 ( 0.65 , 0.71 ) , and 0.694 ( 0.66 , 0.72 ) , respectively ( p < 0.05 for differences ) . The addition of three traditional and non-traditional biomarkers [ β-2 microglobulin , creatinine-based estimated glomerular filtration rate ( eGFR ) , and cystatin C-based eGFR ] to Model 3 significantly improved discrimination ( C-statistic = 0.716 ; p = 0.003 ) and accuracy of 10-year risk prediction for major complications in people with diabetes ( midpoint percentiles of lowest and highest deciles of predicted risk changed from 18 - 68 % to 12 - 87 % ) . CONCLUSIONS These biomarkers , particularly those of kidney filtration , may help distinguish between people at low versus high risk of long-term major complications BACKGROUND It is unclear whether models that include hemoglobin A(1c ) ( HbA(1c ) ) levels only for diabetic patients improve the ability to predict cardiovascular disease ( CVD ) risk compared with the currently recommended classification of diabetes as a cardiovascular risk equivalent . METHODS A total of 24 674 women ( including 685 diabetic participants at baseline ) and 11 280 men ( including 563 diabetic participants at baseline ) were followed up prospect ively for cardiovascular disease ( CVD ) . One hundred twenty-five CVD events occurred in diabetic women ( 666 in nondiabetic women ) , and 170 events occurred in diabetic men ( 1382 in nondiabetic men ) . Models for CVD risk were generated separately for men and women using the traditional CVD risk factors with the addition of a term for HbA(1c ) levels only for diabetic individuals . In diabetic participants , the result ing predicted risks were compared with classification of diabetes as a cardiovascular risk equivalent ( 10-year CVD risk of at least 20 % ) . RESULTS In women , the models including HbA(1c ) levels in diabetic participants improved the C statistic by 0.177 ( P < .001 ) over the risk equivalence model and showed improved reclassification ( net reclassification improvement [ NRI ] of 26.7 % [ P = .001 ] ) . In men , the improvements were more modest but still statistically significant ( C statistic change of 0.039 [ P = .02 ] ; NRI of 9.2 % [ P = .04 ] ) . Including HbA(1c ) levels also improved prediction over a dichotomous term for diabetes in women ( NRI of 11.8 % [ P = .03 ] ) but not in men . CONCLUSIONS In both women and men with diabetes at baseline , we observed significant improvements in predictive ability of CVD risk using models incorporating HbA(1c ) levels compared with classification of diabetes as a cardiovascular risk equivalent OBJECTIVES We assessed the performance of the UK Prospect i ve Diabetes Study ( UKPDS ) outcomes model in predicting the risk of myocardial infa rct ion ( MI ) and stroke in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care ( ADDITION-Europe ) a trial cohort of patients with screen-detected type 2 diabetes from the United Kingdom , Denmark , and The Netherl and s. METHODS We estimated the 5-year accumulated risk of MI and stroke for 2899 screen-detected people with type 2 diabetes by using the UKPDS outcomes model ( version 1.3 ) . We compared the predicted and actual risks by country and by intervention group ( routine care ; intensive multifactorial treatment ) . We assessed discrimination and goodness of fit by using area under receiver operating characteristic curves and the Hosmer-Lemeshow chi-square test . Multiple imputations were used to overcome missing data . RESULTS The UKPDS outcomes model overestimated the risk of MI and stroke . Mean predicted/actual ratios of 5-year accumulated risk were 2.31 for MI in the routine care group and 3.97 in the intensive multifactorial treatment group and 1.59 and 1.48 for stroke , respectively . The differences in absolute risk between the intervention groups were underestimated for MI ( observed vs. predicted : 0.0127 vs. 0.0009 ) and slightly overestimated for stroke ( -0.0013 vs. -0.0004 ) . The area under the receiver operating characteristic curve was 0.72 ( 95 % confidence interval 0.66 - 0.79 ) for MI and 0.70 ( 95 % confidence interval 0.64 - 0.77 ) for stroke . The Hosmer-Lemeshow test statistic was nonsignificant in all groups . The model performed better in absolute risk prediction in Denmark and the United Kingdom than in The Netherl and s. CONCLUSIONS The UKPDS outcomes model has moderate discriminatory ability in the ADDITION-Europe trial cohort but overestimated absolute risk . The model may need updating for cardiovascular disease risk prediction in contemporary diabetes population s where patients may be diagnosed earlier in the disease trajectory and in whom cardiovascular risk is therefore lower OBJECTIVE To evaluate the performance of the UK Prospect i ve Diabetes Study Risk Engine ( UKPDS-RE ) for predicting the 10-year risk of cardiovascular disease end points in an independent cohort of U.K. patients newly diagnosed with type 2 diabetes . RESEARCH DESIGN AND METHODS This was a retrospective cohort study using routine health care data collected between April 1998 and October 2011 from ∼350 U.K. primary care practice s contributing to the Clinical Practice Research Data link ( CPRD ) . Participants comprised 79,966 patients aged between 35 and 85 years ( 388,269 person-years ) with 4,984 cardiovascular events . Four outcomes were evaluated : first diagnosis of coronary heart disease ( CHD ) , stroke , fatal CHD , and fatal stroke . RESULTS Accounting for censoring , the observed versus predicted 10-year event rates were as follows : CHD 6.1 vs. 16.5 % , fatal CHD 1.9 vs. 10.1 % , stroke 7.0 vs. 10.1 % , and fatal stroke 1.7 vs. 1.6 % , respectively . The UKPDS-RE showed moderate discrimination for all four outcomes , with the concordance index values ranging from 0.65 to 0.78 . CONCLUSIONS The UKPDS stroke equations showed calibration ranging from poor to moderate ; however , the CHD equations showed poor calibration and considerably overestimated CHD risk . There is a need for revised risk equations in type 2 diabetes |
12,485 | 25,819,310 | Multi-system reactions were most commonly studied , followed by central nervous system and mental and behavioural disorders .
Vaccines were most frequently prescribed followed by corticosteroids , general anaesthetics and antidepressants .
CONCLUSIONS Routine electronic healthcare records were increasingly reported to be used for pharmacovigilance in children . | AIMS A systematic review of the literature published in English over 10 years was undertaken in order to describe the use of electronic healthcare data in the identification of potential adverse drug reactions ( ADRs ) in children . | Indirect evidence is accumulating for an association between antibiotic use , especially in early childhood , and long-term immunologic health . The authors evaluated the association between antibiotic use in childhood and subsequent development of type 1 diabetes . A nationwide cohort study of all Danish singleton children born during 1995 - 2003 ( n = 606,420 ) was conducted . Incidence rate ratios for type 1 diabetes comparing children according to antibiotic use were estimated . Antibiotic use was classified according to class , number of uses , and age at use . Use of any antibiotic was not associated with type 1 diabetes ( rate ratio = 1.16 , 95 % confidence interval : 0.91 , 1.50 ) . Evaluation of type 1 diabetes risk according to number of courses of any antibiotic yielded no association between antibiotic use and type 1 diabetes , with an increase in rate ratio per course of 1.02 ( 95 % confidence interval : 0.97 , 1.07 ) . No specific class of antibiotics was associated with type 1 diabetes , no specific age of use was associated with type 1 diabetes , and no specific age at onset of type 1 diabetes was associated with antibiotics . In a large nationwide prospect i ve study , no association between antibiotic use and type 1 diabetes was found among Danish children OBJECTIVES To apply an institutional clinical data warehouse ( CDW ) to the assessment of adverse drug reactions ( ADRs ) and demonstrate its utility through a specific example . METHODS We modeled the process for assessing ADRs through retrospective cohort design by using CDW at the Osaka University Hospital as follows : 1 ) We defined a drug X , an adverse drug reaction ( ADR ) Y , and a laboratory measurement Z to assess Y during a given study period ; 2 ) we excluded those whose Z value exceeded the defined criteria or were not available at the inception of the cohort ; 3 ) we divided the patients into two groups based on exposure or non-exposure to X ; 4 ) we matched the patient characteristics between the two groups through stratification and r and omization ; and 5 ) we compared the frequency of patients who presented Y during the study period between the two groups . Aminoglycoside and Cephalosporin associated nephrotoxicity in pediatric in patients was used as an example to demonstrate the usefulness of this approach . RESULTS Our evaluation indicates that there is an increased risk of nephrotoxicity for pediatric in patients who were prescribed cephalosporin either alone or in combination with aminoglycoside ; further , aminoglycoside tends to increase the cephalosporin-associated nephrotoxicity . CONCLUSIONS Our findings are consistent with those drawn from other studies , indicating that the method of applying an institutional CDW is useful for assessing ADRs BACKGROUND The Oka strain of live attenuated varicella virus was licensed for use in healthy children in the United States in March , 1995 . We report a postmarketing evaluation of the short term safety of this vaccine within Kaiser Permanente . METHODS After licensure varicella vaccination was introduced into the preventive care program of the Northern California Kaiser Permanente Medical Care Program . Potential adverse events after vaccination with varicella vaccine were identified from automated clinical data bases of hospitalizations , emergency room visits and clinic visits . Deaths were identified from automated clinical data bases at Kaiser as well as from the State death records for California . To evaluate safety , rates of diagnosis-specific events in the risk periods were compared with the rates of such diagnosis-specific events in two self control and one historical control period . RESULTS During the study period of April 1 , 1995 , to December 31 , 1996 , a total of 89753 adults and children received varicella vaccine . A total of 3200 relative risks were calculated , and of these 5 hospital diagnostic categories , 9 emergency visit diagnostic categories and 30 outpatient diagnostic categories demonstrated at least 1 relative risk with a P value of < 0.05 in 1 or more age groups and in comparisons with 1 control period or more . The p value for these tests was not adjusted for multiple comparisons . Of these categories 14 demonstrated an increased risk either in more than 1 age group or against more than 1 comparison group . These categories included elective procedures , febrile seizure , febrile illness , well child , acute gastroenteritis , varicella , congenital anomaly , " rule out sepsis , " trauma , viral syndrome , apnea , back pain , congenital valvular heart disease and vision evaluation for glasses . Of these the outcomes of elective procedure , congenital anomaly , congenital valvular heart disease , well child and vision evaluation for glasses were judged not to have a biologically plausible association with vaccination . A second diagnostic grouping included febrile illness , viral illness , febrile seizure and " rule out sepsis . " In an analysis of these events which adjusted for the concomitant administration of M-M-R(II ) vaccine , none of the associations was statistically associated with receipt of varicella vaccine . The diagnostic category of " rule out sepsis " still had a relative risk of 1.95 with P = 0.02 . None of the children in the " rule out sepsis " category had positive bacteriologic cultures from any other normally sterile site . Because of the large number of gastroenteritis cases , we review ed a r and om sample of 100 exposed and 100 unexposed cases . From this review no consistent time association or clustering of any of these events was seen in the exposed follow-up time interval . Only gastroenteritis and negative evaluations for sepsis were thought to be possibly associated with receipt of varicella vaccine . Although there was a statistically significant increased risk over the entire 30 day-period , there was no clustering of these events within the 30-day window . CONCLUSION In this study population of 89753 children and adults , the varicella vaccine ( Oka strain , Merck ) appeared to have a favorable safety profile . In addition rates of varicella-like rash and of breakthrough cases were both low and consistent with the rates observed in prelicensure studies From the early 1990s infants started to receive acellular pertussis vaccine combined with diphtheria and tetanus toxoids ( DTaP ) before live vaccines such as measles , rubella , and mumps vaccines , which contained gelatin as a stabilizer . Then , an increasing number of cases of anaphylactic/allergic reactions to those live vaccines were reported . Almost all these cases had a previous history of receiving three or four doses of DTaP containing gelatin . Anaphylactic/allergic reactions to live measles vaccine were analyzed using information obtained from the Reporting System , a retrospective study , as well as from the Monitoring System , a prospect i ve study . Dramatic decreases in anaphylactic/allergic reactions to live measles vaccines were observed immediately after each manufacturer marketed gelatin-free or gelatin (hypo-allergic)-containing live measles vaccine , and since the end of 1998 reports on anaphylactic/allergic reactions to live measles vaccine have almost ceased BACKGROUND The ongoing debate on the incidence and types of iatrogenic injuries in American hospitals has been informed primarily by the Harvard Medical Practice Study , which analyzed hospitalizations in New York in 1984 . The generalizability of these findings is unknown and has been question ed by other studies . OBJECTIVE We used methods similar to the Harvard Medical Practice Study to estimate the incidence and types of adverse events and negligent adverse events in Utah and Colorado in 1992 . DESIGN AND SUBJECTS We selected a representative sample of hospitals from Utah and Colorado and then r and omly sample d 15,000 nonpsychiatric 1992 discharges . Each record was screened by a trained nurse- review er for 1 of 18 criteria associated with adverse events . If > or = 1 criteria were present , the record was review ed by a trained physician to determine whether an adverse event or negligent adverse event occurred and to classify the type of adverse event . MEASURES The measures were adverse events and negligent adverse events . RESULTS Adverse events occurred in 2.9+/-0.2 % ( mean+/-SD ) of hospitalizations in each state . In Utah , 32.6+/-4 % of adverse events were due to negligence ; in Colorado , 27.4+/-2.4 % . Death occurred in 6.6+/-1.2 % of adverse events and 8.8+/-2.5 % of negligent adverse events . Operative adverse events comprised 44.9 % of all adverse events ; 16.9 % were negligent , and 16.6 % result ed in permanent disability . Adverse drug events were the leading cause of nonoperative adverse events ( 19.3 % of all adverse events ; 35.1 % were negligent , and 9.7 % caused permanent disability ) . Most adverse events were attributed to surgeons ( 46.1 % , 22.3 % negligent ) and internists ( 23.2 % , 44.9 % negligent ) . CONCLUSIONS The incidence and types of adverse events in Utah and Colorado in 1992 were similar to those in New York State in 1984 . Iatrogenic injury continues to be a significant public health problem . Improving systems of surgical care and drug delivery could substantially reduce the burden of iatrogenic injury OBJECTIVE Pediatric interventional radiologists are frequently challenged when faced with organ biopsies . Because of the need for patient immobility and the potential risk of morbidity with patient movement during biopsies , many radiologists prefer general anesthesia to sedation . We present our experience with radiologist-supervised ketamine sedation in pediatric patients undergoing renal and hepatic biopsies . MATERIAL S AND METHODS Quality assurance data were accessed from a computerized data base that prospect ively collects demographics , outcome parameters , and adverse events on all patients who receive ketamine sedation . Patients received an IV ketamine bolus of 2 mg/kg followed by a continuous infusion of ketamine of up to 150 mcg/kg/min titrated to the responsiveness of the patient . RESULTS Sixty-five children received ketamine for liver ( n = 35 ) and renal ( n = 30 ) biopsies . The mean age of the study group was 7.0 + /- 2.7 ( SD ) years . The cohort included patients with an American Society of Anesthesiologists ( ASA ) physical status classification of ASA 1 ( 3 % ) , ASA 2 ( 78 % ) , and ASA 3 ( 19 % ) . The duration of ketamine sedation averaged 39 + /- 20 ( SD ) minutes , with an average procedure time of 32 + /- 19 ( SD ) minutes . All procedures were successfully completed , and there were no major adverse events . CONCLUSION Interventional radiologists performing solid organ biopsies in the pediatric population often use general anesthesia to ensure immobility , adequate analgesia , and safe conditions . Our experience suggests that interventional radiologists may supervise a nurse-administered ketamine protocol to provide safe , effective analgesia and sedation for liver and renal biopsies UNLABELLED Recent reports out of Japan have linked therapeutic use of the oral neuraminidase inhibitor oseltamivir with adverse neuropsychiatric outcomes in adolescents . OBJECTIVE To assess if protective measures should be taken to mitigate potential adverse outcomes among United States Department of Defense ( DoD ) pediatric beneficiaries who are prescribed oseltamivir therapeutically . STUDY GROUP DoD healthcare beneficiaries , ages 1 through 21 years , who received a diagnosis of influenza from 1 October 2006 through 30 September 2007 . METHODS A retrospective cohort study using electronic healthcare service and pharmacy fill . Cross tabulations and propensity-adjusted logistic regression analyses were performed to compare the frequency of adverse neuropsychiatric outcomes among those treated therapeutically with oseltamivir with those that were not . RESULTS The prevalences of neuropsychiatric diagnoses following the influenza diagnosis overall and among the treated and untreated groups were 3.5 % , 3.0 % , and 3.8 % , respectively ( p < .05 ) . A statistically significant protective effect was associated with oseltamivir treatment ( prevalence odds ratio ( POR ) = 0.82 ( 95 % CI , 0.69 , 0.96 ) ) in a propensity-adjusted regression model . The model significantly associated increasing patient age with the likelihood of an adverse neuropsychiatric outcome , but the associations with patient gender and parental rank , a proxy used for socioeconomic status , were not statistically Significant . CONCLUSIONS Our retrospective study found no evidence that oseltamivir treatment for influenza increased the risk of adverse neuropsychiatric outcomes among the study population . An additional study focusing on prospect i ve medical surveillance of influenza patients is warranted A retrospective cohort design of Medicaid medical and pharmacy cl aims for 1996 through 2005 was employed for 14 171 children and adolescents prescribed an antidepressant medication and a r and om sample of 4500 children not treated with any class of psychotropic medication to compare the prevalence rates of cardiovascular and neurological adverse events . The treated cohort evinced a higher prevalence of cardiovascular events , orthostatic hypotension , seizures , insomnia , and headaches . In the treated cohort , patients were at a significantly higher risk for incident cardiovascular events when exposed to selective serotonin reuptake inhibitors and weight-inducing antidepressants , mood stabilizers , and antipsychotics . Incident orthostatic hypotension was associated with weight-inducing antidepressants and mood stabilizers . Incident seizures and extrapyramidal symptoms were unrelated to antidepressant or co-prescribed psychotropic medications , but both were significantly associated with comorbid central nervous system , organic brain/mental retardation , or preexisting cardiovascular or cerebrovascular conditions . Headaches and dizziness were significantly related to taking mood stabilizers BACKGROUND In a sample of 30,195 r and omly selected hospital records , we identified 1133 patients ( 3.7 percent ) with disabling injuries caused by medical treatment . We report here an analysis of these adverse events and their relation to error , negligence , and disability . METHODS Two physician- review ers independently identified the adverse events and evaluated them with respect to negligence , errors in management , and extent of disability . One of the authors classified each event according to type of injury . We tested the significance of differences in rates of negligence and disability among categories with at least 30 adverse events . RESULTS Drug complications were the most common type of adverse event ( 19 percent ) , followed by wound infections ( 14 percent ) and technical complications ( 13 percent ) . Nearly half the adverse events ( 48 percent ) were associated with an operation . Adverse events during surgery were less likely to be caused by negligence ( 17 percent ) than nonsurgical ones ( 37 percent ) . The proportion of adverse events due to negligence was highest for diagnostic mishaps ( 75 percent ) , noninvasive therapeutic mishaps ( " errors of omission " ) ( 77 percent ) , and events occurring in the emergency room ( 70 percent ) . Errors in management were identified for 58 percent of the adverse events , among which nearly half were attributed to negligence . CONCLUSIONS Although the prevention of many adverse events must await improvements in medical knowledge , the high proportion that are due to management errors suggests that many others are potentially preventable now . Reducing the incidence of these events will require identifying their causes and developing methods to prevent error or reduce its effects BACKGROUND A combined measles , mumps , rubella , varicella live vaccine ( MMRV , Merck and Co. , Inc. , US ) was recently licensed in the US . Pre-licensure clinical trial data showed a significant increase in fever in days 5 - 12 following MMRV vaccination as compared to the vaccines given separately ( MMR+V ) . This post-licensure retrospective cohort study was undertaken to assess the incidence of febrile convulsion following MMRV . METHODS Children ages 12 - 60 months who received a first dose of MMRV in February 2006-June 2007 in a managed care organization were included in the study . Subjects were optimally matched on age , sex , and calendar date of vaccination to children who received MMR+V concomitantly in November 2003-January 2006 , before MMRV licensure . Potential cases of febrile convulsion were identified through administrative data and adjudicated by expert panel , according to pre-specified criteria . RESULTS During the 30 days post-vaccination , there were 128 and 94 potential convulsion cases among the 31,298 children in the MMRV and MMR+V cohorts , respectively . After review of available medical charts and adjudication , there were 84 cases of confirmed febrile convulsion , 44 ( 1.41/1000 ) and 40 ( 1.28/1000 ) in the MMRV and MMR+V cohorts , respectively ( RR=1.10 , 95 % CI=0.72 , 1.69 ) . In days 5 - 12 following vaccination , a pre-specified period of interest , the respective numbers were 22 ( 0.70/1000 ) and 10 ( 0.32/1000 ) ( RR=2.20 , 95 % CI=1.04 , 4.65 ) . CONCLUSION These data suggest that the risk of febrile convulsion is increased in days 5 - 12 following vaccination with MMRV as compared to MMR+V given separately during the same visit , when post-vaccination fever and rash are also increased in clinical trials . While there was no evidence of an increase in the overall month following vaccination , the elevated risk during this time period should be communicated and needs to be balanced with the potential benefit of a combined vaccine OBJECTIVE This study was design ed to evaluate safety , efficacy , and success of adding IV midazolam to an established IV pentobarbital protocol for pediatric sedation for radiologic imaging . Outcomes included sedation and discharge times as well as adverse events SUBJECTS AND METHODS This prospect i ve study compared two different sedation protocol s developed by the radiology sedation committee and approved by the hospital sedation committee at our institution . Patients in the pentobarbital group received IV pentobarbital alone , and patients in the pentobarbital -- midazolam group received a combination of IV pentobarbital and midazolam . A total of 1070 infants and children were enrolled , and sedation data were entered into a computer data base and review ed at bimonthly radiology sedation committee meetings for safety , efficacy , efficiency , failed sedations , and adverse outcomes . RESULTS Mean age distribution , sex , American Society of Anesthesiologists physical status classification , fasting status , weight , and types of examinations were similarly distributed between the two study groups . Analysis of variance indicated longer times were required to se date and to discharge patients who had received pentobarbital -- midazolam ( p < 0.001 for both times ) , even after adjusting for differences in the patients ' ages and weights . The pentobarbital -- midazolam group required more time to be successfully se date d and more time to discharge from the recovery room . The rates of adverse events and failed sedations were similar for both groups . CONCLUSION Midazolam does not have a beneficial effect on pentobarbital sedation and has no effect on the rate of adverse events . The prolonged time needed both to se date and to discharge ( timed from the initial dose of sedation ) pediatric patients who have received midazolam should discourage physicians from combining it with pentobarbital for pediatric sedation Abstract Background : Adverse drug events ( ADEs ) are an important problem in all hospitalized patients as these events represent medication-related patient harm . Few epidemiologic data exist regarding ADEs in the pediatric inpatient setting and , in particular , the economic impact of such ADEs upon the healthcare sector . Objective : To evaluate the incidence , preventability , and seriousness of ADEs and potential ADEs occurring in hospitalized children and to examine the cost implication s of these ADEs . Methods : This was a prospect i ve observational cohort study conducted in the pediatric , neonatal intensive care unit ( NICU ) , and postnatal wards of a university-affiliated urban general hospital in Dunedin , New Zeal and ( NZ ) . The study population was all patients admitted to these wards for > 24 hours over a 12-week period from 18 March 2002 to 9 June 2002 . Medication-related events were identified by chart review , attendance at multidisciplinary clinical meetings , parent/carer/child interviews , and voluntary and verbally solicited reports from staff . All suspected medication-related events were review ed by a panel of three health professionals who independently categorized the events and rated them for seriousness , preventability , and causality , using a st and ardized review er form . Costs attributable to ADEs were calculated using both the average cost of a bed day , and specific costs for diagnostic groupings . The main outcome measures of the study were ADEs and potential ADEs . Results : There were 495 eligible study patients , who had a total of 520 admissions and 3037 patient-days of admission , during which 3160 prescription episodes were written . There were 67 ADEs , of which 38 ( 56.7 % ) were classified as preventable , and 77 potential ADEs . ADEs occurred at a rate of 2.1 per 100 prescription episodes , 12.9 per 100 admissions , and 22.1 per 1000 patient-days . Potential ADEs occurred at a rate of 2.4 per 100 prescription episodes , 14.6 per 100 admissions , and 25 per 1000 patient-days . Although the greatest number ( and rate per 100 admissions ) of ADEs occurred in NICU patients , surgical pediatric ward patients had the greatest rate of ADEs per 1000 patient-days . Few events occurred in postnatal patients . Forty-six percent of ADEs were classified as being serious ; 15 % were deemed to result in persistent disability or were classified as life threatening . Potential ADEs were deemed more likely to be serious with 82 % classified as potentially serious events ; 33 % were deemed as having the potential to result in persistent disability , or the potential to cause a life-threatening event . Fifteen ADEs were judged to have caused the hospital admission or to have prolonged hospital stay . The total number of days attributed to ADEs was 92 ( range 1–26 days ) ; of these , 58 were deemed preventable days and 34 non-preventable days . This extrapolates to a total annual cost of $ NZ235 214 ( 2002 values ) to the pediatric service , subdivided into $ NZ148 287 for preventable ADEs and $ NZ86927 for non-preventable ADEs . Conclusion : ADEs and potential ADEs represent a considerable hazard for the pediatric inpatient population and ADEs represent a large cost imposition upon the healthcare sector . Over half of the ADEs were deemed preventable . This highlights the importance of developing strategies to prevent and ameliorate ADEs both to improve the quality of patient care and to reduce healthcare costs The association between treatment with Selective serotonin reuptake inhibitors ( SSRIs ) and suicide in children and adolescents on the individual and ecological level were examined in a nationwide Danish pharmacoepidemiological register-linkage study including all persons aged 10 - 17 years treated with antidepressants during the period 1995 - 1999 ( n=2,569 ) and a r and omly selected control population ( n=50,000 ) . A tripartite approach was used . In Part 1 , changes in youth suicide and use of antidepressants were examined . In Part 2 , we made an assessment of youth suicide characteristics . In Part 3 , we analysed the relative risk ( RR ) of suicide according to antidepressant treatment corrected for psychiatric hospital contact to minimize the problem of confounding by indication . The use of SSRIs among children and adolescents increased substantially during the study period , but the suicide rate remained stable ( Part 1 ) . Among 42 suicides nationally aged 10 - 17 years at death , none was treated with SSRIs within 2 weeks prior to suicide ( Part 2 ) . There was an increased rate of suicide associated with SSRIs ( RR=4.47 ) , however , not quite significant ( 95 % CI : 0.95 - 20.96 ) , when adjusted for severity of illness ( Part 3 ) . Conclusively , we were not able to identify an association between treatment with SSRIs and completed suicide among children and adolescents AIMS To investigate the potential relationship between off-label drug use and increased risk of adverse drug reactions in paediatric out patients . METHODS A prospect i ve pharmacovigilance survey of drug prescribing in office based paediatricians was carried out in Haute-Garonne County ( south west of France ) . RESULTS The study involved a sample of 1419 children under 16 years old . Forty-two percent of patients were exposed to at least one off-label prescription . The incidence of adverse drug reactions was 1.41 % ( 95 % CI 0.79 , 2.11 ) . Off-label drug use was significantly associated with adverse drug reactions ( relative risk 3.44 ; 95 % CI 1.26 , 9.38 ) , particularly when it was due to an indication different than that defined in the Summary Product Characteristics ( relative risk 4.42 ; 95 % CI 1.60 , 12.25 ) . CONCLUSIONS Our data suggest an increasing risk of adverse drug reactions related to off-label drug use . This risk would be acceptable if further studies prove the potential benefit of such a drug use |
12,486 | 31,188,152 | Most studies included low-risk surgical patients and considerable variation was observed between prehabilitation programmes in terms of supervision , training context , frequency , intensity , duration and training type .
CONCLUSION : The content of prehabilitation programmes was heterogeneous .
Studies with a high therapeutic validity found unequivocal evidence that prehabilitation had beneficial effects on postoperative outcomes . | BACKGROUND : Although prehabilitation programmes for patients undergoing major intra-abdominal cancer surgery have been shown to improve pre-operative physical fitness , the conclusions regarding any postoperative benefits are inconsistent .
OBJECTIVES : The aim of this study was to evaluate the content of and the outcome measures used in studies of prehabilitation programmes for these patients .
It was hypothesised that the content of prehabilitation programmes is often therapeutically invalid , and that the postoperative outcomes assessed are inadequate to evaluate the impact of complications . | Background Of all older patients that opt for elective colorectal surgery , approximately one-third has one or more postoperative complications , particularly those patients with a low cardiorespiratory fitness ( ventilatory anaerobic threshold ( VAT ) < 11 mL/kg/min ) . A physical exercise training program prior to surgery ( prehabilitation ) can improve their cardiorespiratory fitness . It remains to be seen whether prehabilitation also reduces postoperative complications , as most of the studies so far were rather underpowered , heterogeneous , and biased toward selection of patients with a lower risk of postoperative complications . The primary objective of this study is to evaluate the effects of a three-week prehabilitation program on 30-day postoperative complications in patients with a VAT < 11 mL/kg/min planned for elective colorectal resection for colorectal cancer or dysplasia . Methods In this multicenter prospect i ve r and omized controlled trial , patients ≥ 60 years with colorectal cancer or dysplasia grade I , II , or III , planned for elective colorectal resection in two hospitals in the Netherl and s , will be recruited . Eligible patients must have a score ≤ 7 metabolic equivalents on the veterans-specific activity question naire , and should be able to perform a cardiopulmonary exercise test . A total of 86 patients will be r and omized ( block-stratified r and omization ) to prehabilitation ( intervention group ) or usual care ( control group ) . For final inclusion , VAT should be < 11 mL/kg/min . Three times a week for 3 weeks , a 60-min supervised prehabilitation session will be completed in community physical therapy practice s by the 43 patients in the prehabilitation group , consisting of moderate-to-high intensity interval training to improve cardiorespiratory fitness , and resistance training to improve peripheral muscle strength . Additionally , patients perform home exercises twice a week on a moderate intensity level . The 43 patients in the usual care group will receive usual care . Discussion Optimizing preoperative physical fitness may decrease the postoperative complication rate , may lead to fewer reoperations , less intense clinical care , a shorter length of stay , a more effective surgical planning ( process-optimization ) , fewer readmissions , less intense rehabilitation , shorter rehabilitation period , earlier resumption of work , enhance patient perceived health-related quality of life , and promote performance in daily life . Cost-effectiveness should therefore be expected and evaluated . Trial registration Medical Ethics Committee Twente , Enschede , the Netherl and s ( NL45001.044.13 , September 3 , 2013 ) ; Netherl and s Trial Register ( NTR ; NTR4032 , June 14 , 2013 ) CONTEXT Postoperative pulmonary complications ( PPCs ) after coronary artery bypass graft ( CABG ) surgery are a major source of morbidity and mortality , and increase length of hospital stay and re source utilization . The prehospitalization period before CABG surgery may be used to improve a patient 's pulmonary condition . The efficacy of preoperative inspiratory muscle training ( IMT ) in reducing the incidence of PPCs in high-risk patients undergoing CABG surgery has not yet been determined . OBJECTIVE To evaluate the prophylactic efficacy of preoperative IMT on the incidence of PPCs in high-risk patients scheduled for elective CABG surgery . DESIGN , SETTING , AND PATIENTS A single-blind , r and omized clinical trial conducted at the University Medical Center Utrecht , Utrecht , the Netherl and s , with enrollment between July 2002 and August 2005 . Of 655 patients referred for elective CABG surgery , 299 ( 45.6 % ) met criteria for high risk of developing PPCs , of whom 279 were enrolled and followed up until discharge from hospital . INTERVENTION Patients were r and omly assigned to receive either preoperative IMT ( n = 140 ) or usual care ( n = 139 ) . Both groups received the same postoperative physical therapy . MAIN OUTCOME MEASURES Incidence of PPCs , especially pneumonia , and duration of postoperative hospitalization . RESULTS Both groups were comparable at baseline . After CABG surgery , PPCs were present in 25 ( 18.0 % ) of 139 patients in the IMT group and 48 ( 35.0 % ) of 137 patients in the usual care group ( odds ratio [ OR ] , 0.52 ; 95 % confidence interval [ CI ] , 0.30 - 0.92 ) . Pneumonia occurred in 9 ( 6.5 % ) of 139 patients in the IMT group and in 22 ( 16.1 % ) of 137 patients in the usual care group ( OR , 0.40 ; 95 % CI , 0.19 - 0.84 ) . Median duration of postoperative hospitalization was 7 days ( range , 5 - 41 days ) in the IMT group vs 8 days ( range , 6 - 70 days ) in the usual care group by Mann-Whitney U statistic ( z = -2.42 ; P = .02 ) . CONCLUSION Preoperative IMT reduced the incidence of PPCs and duration of postoperative hospitalization in patients at high risk of developing a pulmonary complication undergoing CABG surgery . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N17691887 Background : As global initiatives increase patient access to surgical treatments , there remains a need to underst and the adverse effects of surgery and define appropriate levels of perioperative care . Methods : We design ed a prospect i ve international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries . The primary outcome was in-hospital complications . Secondary outcomes were death following a complication ( failure to rescue ) and death in hospital . Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay . A single definition of critical care was used for all countries . Results : A total of 474 hospitals in 19 high- , 7 middle- and 1 low-income country were included in the primary analysis . Data included 44 814 patients with a median hospital stay of 4 ( range 2–7 ) days . A total of 7508 patients ( 16.8 % ) developed one or more postoperative complication and 207 died ( 0.5 % ) . The overall mortality among patients who developed complications was 2.8 % . Mortality following complications ranged from 2.4 % for pulmonary embolism to 43.9 % for cardiac arrest . A total of 4360 ( 9.7 % ) patients were admitted to a critical care unit as routine immediately after surgery , of whom 2198 ( 50.4 % ) developed a complication , with 105 ( 2.4 % ) deaths . A total of 1233 patients ( 16.4 % ) were admitted to a critical care unit to treat complications , with 119 ( 9.7 % ) deaths . Despite lower baseline risk , outcomes were similar in low- and middle-income compared with high-income countries . Conclusions : Poor patient outcomes are common after inpatient surgery . Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care . Study registration : IS RCT Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Surgical patients often show physiological and metabolic distress , muscle weakness , and long hospital stays . Physical conditioning might help recovery . We attempted to identify the most responsive measure of aerobic fitness from a four-week pre-surgical aerobic exercise program ( prehabilitation ) in patients undergoing major bowel resection . Twenty-one subjects r and omized two to one ( exercise : control ) scheduled for colorectal surgery . Fourteen subjects [ Body Mass Index ( BMI ) = 27 + /- 6 kg/m(2 ) ; maximal oxygen uptake ( VO(2max ) ) = 22 + /- 10 ml/kg/min ] underwent 3.8 + /- 1.2 weeks ( 27 + /- 8 sessions ) of progressive , structured pre-surgical aerobic exercise training at 40 to 65 % of heart rate reserve ( % HRR ) . Peak power output was the only maximal measure that was responsive to training [ 26 + /- 27 % , Effects Size ( ES ) = 0.24 ; St and ardized Response Mean ( SRM ) = 1.05 ; p < 0.05 ] . For the submaximal measures , heart rate and oxygen uptake during submaximal exercise was most responsive to training ( decrease by 13 % + /- 15 % , ES = -0.24 ; SRM = -0.57 ; and 7 % + /- 6 % , ES = -0.40 ; SRM -0.97 ; p < 0.05 ) at an exercise intensity of 76 + /- 47 W. There was no change to maximal or submaximal measures in the control group . The distance walked over six minutes improved in both groups ( by approximately 30 m ) , but the effect size and t-statistic were higher in the exercise group . Heart rate and oxygen uptake during submaximal exercise , and peak power output are the most responsive measures to four weeks of prehabilitation in subjects with low initial fitness Objective : The aim of this study was to assess the impact of personalized prehabilitation on postoperative complications in high-risk patients undergoing elective major abdominal surgery . Summary Background Data : Prehabilitation , including endurance exercise training and promotion of physical activity , in patients undergoing major abdominal surgery has been postulated as an effective preventive intervention to reduce postoperative complications . However , the existing studies provide controversial results and show a clear bias toward low-risk patients . Methods : This was a r and omized blinded controlled trial . Eligible c and i date s accepting to participate were blindly r and omized ( 1:1 ratio ) to control ( st and ard care ) or intervention ( st and ard care + prehabilitation ) groups . Inclusion criteria were : i ) age > 70 years ; and /or , ii ) American Society of Anesthesiologists score III/IV . Prehabilitation covered 3 actions : i ) motivational interview ; ii ) high-intensity endurance training ; and promotion of physical activity . The main study outcome was the proportion of patients suffering postoperative complications . Secondary outcomes included the endurance time ( ET ) during cycle-ergometer exercise . Results : We r and omized 71 patients to the control arm and 73 to intervention . After excluding 19 patients because of changes in the surgical plan , 63 controls and 62 intervention patients were included in the intention-to-treat analysis . The intervention group enhanced aerobic capacity [ & Dgr;ET 135 ( 218 ) % ; P < 0.001 ) , reduced the number of patients with postoperative complications by 51 % ( relative risk 0.5 ; 95 % confidence interval , 0.3–0.8 ; P = 0.001 ) and the rate of complications [ 1.4 ( 1.6 ) and 0.5 ( 1.0 ) ( P = 0.001 ) ] as compared with controls . Conclusion : Prehabilitation enhanced postoperative clinical outcomes in high-risk c and i date s for elective major abdominal surgery , which can be explained by the increased aerobic capacity BACKGROUND The aim of this study was to examine the outcomes of exercise therapy in patients with hepatocellular carcinoma who underwent hepatectomy . METHODS Fifty-one patients with hepatocellular carcinoma were r and omized to diet therapy alone ( n = 25 ) or to exercise in addition to diet therapy ( n = 26 ) . Exercise at the anaerobic threshold of each patient was started 1 month preoperatively , resumed from 1 week postoperatively , and continued for 6 months . RESULTS Whole body mass and fat mass in the exercise group compared with the diet group were significantly decreased at 6 months postoperatively . Fasting serum insulin and the homeostasis model assessment score were also significantly decreased . At 6 months , anaerobic threshold and peak oxygen consumption were significantly increased , while serum insulin and insulin resistance were significantly improved in a high-frequency exercise subgroup compared with a low-frequency group . CONCLUSIONS Perioperative exercise therapy for patients with hepatocellular carcinoma with liver dysfunction may improve insulin resistance associated with hepatic impairment and suggests a benefit to the early resumption of daily exercise after hepatectomy Background : The preoperative period ( prehabilitation ) may represent a more appropriate time than the postoperative period to implement an intervention . The impact of prehabilitation on recovery of function al exercise capacity was thus studied in patients undergoing colorectal resection for cancer . Methods : A parallel-arm single-blind superiority r and omized controlled trial was conducted . Seventy-seven patients were r and omized to receive either prehabilitation ( n = 38 ) or rehabilitation ( n = 39 ) . Both groups received a home-based intervention of moderate aerobic and resistance exercises , nutritional counseling with protein supplementation , and relaxation exercises initiated either 4 weeks before surgery ( prehabilitation ) or immediately after surgery ( rehabilitation ) , and continued for 8 weeks after surgery . Patients were managed with an enhanced recovery pathway . Primary outcome was functional exercise capacity measured using the vali date d 6-min walk test . Results : Median duration of prehabilitation was 24.5 days . While awaiting surgery , functional walking capacity increased ( ≥20 m ) in a higher proportion of the prehabilitation group compared with the rehabilitation group ( 53 vs. 15 % , adjusted P = 0.006 ) . Complication rates and duration of hospital stay were similar . The difference between baseline and 8-week 6-min walking test was significantly higher in the prehabilitation compared with the rehabilitation group ( + 23.7 m [ SD , 54.8 ] vs. −21.8 m [ SD , 80.7 ] ; mean difference 45.4 m [ 95 % CI , 13.9 to 77.0 ] ) . A higher proportion of the prehabilitation group were also recovered to or above baseline exercise capacity at 8 weeks compared with the rehabilitation group ( 84 vs. 62 % , adjusted P = 0.049 ) . Conclusion : Meaningful changes in postoperative functional exercise capacity can be achieved with a prehabilitation program Abstract Background : Prehabilitation has been previously shown to be more effective in enhancing postoperative functional capacity than rehabilitation alone . The purpose of this study was to determine whether a weekly supervised exercise session could provide further benefit to our current prehabilition program , when comparing to st and ard post-surgical rehabilitation . Methods : A parallel-arm single-blind r and omized control trial was conducted in patients scheduled for non-metastatic colorectal cancer resection . Patients were assigned to either a once weekly supervised prehabilitation ( PREHAB+ , n = 41 ) or st and ard rehabilitation ( REHAB , n = 39 ) program . Both multimodal programs were home-based program and consisted of moderate intensity aerobic and resistance exercise , nutrition counseling with daily whey protein supplementation and anxiety-reduction strategies . Perioperative care was st and ardized for both groups as per enhanced recovery after surgery ( ERAS ® ) guidelines . Functional exercise capacity , as determined by the 6-minute walk test distance ( 6MWD ) , was the primary outcome . Exercise quantity , intensity and energy expenditure was determined by the CHAMPS question naire . Results : Both groups were comparable for baseline walking capacity ( PREHAB+ : 448 m [ IQR 375–525 ] vs. REHAB : 461 m [ 419–556 ] , p=.775 ) and included a similar proportion of patients who improved walking capacity ( > 20 m ) during the preoperative period ( PREHAB+ : 54 % vs. REHAB : 38 % , p = .222 ) . After surgery , changes in 6MWD were also similar in both groups . In PREHAB+ , however , there was a significant association between physical activity energy expenditure and 6MWD ( p < .01 ) . Previously inactive patients were more likely to improve functional capacity due to PREHAB+ ( OR 7.07 [ 95 % CI 1.10–45.51 ] ) . Conclusions : The addition of a weekly supervised exercise session to our current prehabilitation program did not further enhance postoperative walking capacity when compared to st and ard REHAB care . Sedentary patients , however , seemed more likely to benefit from PREHAB+ . An association was found between energy spent in physical activity and 6MWD . This information is important to consider when design ing cost-effective prehabilitation programs short-term prognosis of perioperative myocardial infa rct ion in patients undergoing noncardiac surgery : a cohort study . Ann Intern Med 2011 ; 154 : 523–8 5 . Botto F , Alonso-Coello P , Chan MT , et al. Myocardial injury after noncardiac surgery : a large , international , prospect i ve cohort study establishing diagnostic criteria , characteristics , predictors , and 30-day outcomes . Anesthesiology 2014 ; 120 : 564–78 6 . Wa sowicz M , Syed S , Wijeysundera DN , et al. Effectiveness of platelet inhibition on major adverse cardiac events in noncardiac surgery after percutaneous coronary intervention : a prospect i ve cohort study . Br J Anaesth 2016 ; 116 : 493–500 7 . Kubo T , Imanishi T , Takarada S , et al. Assessment of culprit lesionmorphology in acutemyocardial infa rct ion : ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy . J Am Coll Cardiol 2007 ; 50 : 933–9 8 . Ino Y , Kubo T , Tanaka A , et al. Difference of culprit lesion morphologies between ST-segment elevation myocardial infa rct ion and non-ST-segment elevation acute coronary syndrome : an optical coherence tomography study . JACC Cardiovasc Interv 2011 ; 4 : 76–82 9 . Devereaux PJ , Mrkobrada M , Sessler DI , et al. Aspirin in patients undergoing noncardiac surgery . N Engl J Med 2014 ; 370 : 1494–503 10 . Kamel H , Johnston SC , Kirkham JC , et al. Association between major perioperative hemorrhage and stroke or Q-wave myocardial infa rct ion . Circulation 2012 ; 126 : 207–12 11 . Fleisher LA , Fleischmann KE , Auerbach AD , et al. 2014 ACC/ AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery : executive summary : a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines . Circulation 2014 ; 130 : 2215–45 12 . collaborators C-t , Shakur H , Roberts I , et al. Effects of tranexamic acid on death , vascular occlusive events , and blood transfusion in trauma patients with significant haemorrhage ( CRASH-2 ) : a r and omised , placebo-controlled trial . Lancet 2010 ; 376 : 23–32 13 . Roberts I , Perel P , Prieto-Merino D , et al. Effect of tranexamic acid onmortality in patients with traumatic bleeding : prespecified analysis of data from r and omised controlled trial . BMJ 2012 ; 345 : e5839 14 . Kaluza GL , Joseph J , Lee JR , Raizner ME , Raizner AE . Catastrophic outcomes of noncardiac surgery soon after coronary stenting . J Am Coll Cardiol 2000 ; 35 : 1288–94 15 . Devereaux PJ , Yang H , Yusuf S , et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery ( POISE trial ) : a r and omised controlled trial . Lancet 2008 ; 371 : 1839–47 16 . Devereaux PJ , Sessler DI , Leslie K , et al. Clonidine in patients undergoing noncardiac surgery . N Engl J Med 2014 ; 370 : 1504–13 17 . Myles PS , Leslie K , ChanMT , et al. The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery ( ENIGMA-II ) : a r and omised , single-blind trial . Lancet 2014 ; 384 : Background Risk factors , such as the number of pre-existing co-morbidities , the extent of the underlying pathology and the magnitude of the required operation , can not be changed before surgery . It may , however , be possible to improve the cardiopulmonary fitness of the patient with an individualised exercise program . We are performing a r and omised controlled trial ( RCT ) assessing the impact of High Intensity Interval Training ( HIIT ) on preoperative cardiopulmonary fitness and postoperative outcomes in patients undergoing major abdominal surgery . Methods Consecutive eligible patients undergoing elective abdominal surgery are being r and omised to HIIT or st and ard care in a 1:1 ratio . Participants allocated to HIIT will perform 14 exercise sessions on a stationary cycle ergometer , over a period of 4–6 weeks before surgery . The sessions , which are individualised , aim to start with ten repeated 1-min blocks of intense exercise with a target of reaching a heart rate exceeding 90 % of the age predicted maximum , followed by 1 min of lower intensity cycling . As endurance improves , the duration of exercise is increased to achieve five 2-min intervals of high intensity exercise followed by 2 min of lower intensity cycling . Each training session lasts approximately 30 min . The primary endpoint , change in peak oxygen consumption ( Peak VO2 ) measured during cardiopulmonary exercise testing , is assessed at baseline and before surgery . Secondary endpoints include postoperative complications , length of hospital stay and three clinical ly vali date d scores : the surgical recovery scale ; the postoperative morbidity survey ; and the SF-36 quality of life score . The st and ard deviation for changes in Peak VO2 will be assessed after the first 30 patients and will be used to calculate the required sample size . Discussion We want to assess if 14 sessions of HIIT is sufficient to improve Peak VO2 by 2 mL/kg/min in patients undergoing major abdominal surgery and to explore the best clinical endpoint for a subsequent RCT design ed to assess if improving Peak VO2 will translate into improving clinical outcomes after surgery . Trial registration Australian New Zeal and Clinical Trials Registry , ACTRN12617000587303 . Registered on 26 April 2017 Background A physically active lifestyle in older people contributes to the preservation of good health . We assessed the influence of physiotherapy on daily functioning among community dwelling older people ( 75 + ) with complex health problems identified with screening , versus usual care . We also compared functional task exercise ( FTE ) , with problems prioritized by older people , trained in the home environment , versus usual preventive physical therapy ( PPT ) . Methods Design : FTE and PPT were compared in a r and omized controlled trial ( RCT ) . Both interventions were compared with daily functioning in an observational study : control group . Setting / Participants : Community-dwelling persons aged ≥75 years with daily activity limitations enlisted in 83 general practice s ( n = 155 ) . Interventions : Both intervention groups ( FTE , n = 76 and PPT , n = 79 ) received individual , 30 min treatments . The control group ( n = 228 ) did not get any experimental intervention offered . Measurements : Groningen Activities of Daily Living Restriction Scale (GARS).Statistical analyses : Linear Mixed Model analysis , correcting for age , sex , baseline scores and clustering by physiotherapist were used to compare the different groups . Results At baseline , 74 % percent of the intervention trial group was female vs 79 % in the control group . Median ages were 83.9 and 84.7 respectively . The median baseline GARS-score for the control group was 41.0 ( 25 and 75 percentile ) : 35.0 ; 48.0 ) and 40.0 ( 25 and 75 percentile : 32.3 ; 46.0 ) for the intervention group ( FTE + PPT ) . The mean change over time was 3.3 ( 2.5 ; 4.1 ) for the control group . Mean difference in change over time between the intervention ( FTE + PPT ) and the control group was − 2.5 ( − 4.3 ; − 0.6 ) ( p = .009).Between FTE and PPT the difference in change was − 0.4 ( 95 % CI : -2.3 ; 3.0 , p = 0.795 ) . Conclusion An exercise intervention led by physiotherapists may slow down decline in self-reported daily functioning in older persons with daily activity limitations , identified by pro-active case finding . Trial registration Netherl and s trial register ( NTR2407 ) . Registered 6th of July 2010 Background Colorectal cancer ( CRC ) is the second most prevalent type of cancer in the world . Surgery is the only curative option . However , postoperative complications occur in up to 50 % of patients and are associated with higher morbidity and mortality rates , lower health related quality of life ( HRQoL ) and increased expenditure in health care . The number and severity of complications are closely related to preoperative functional capacity , nutritional state , psychological state , and smoking behavior . Traditional approaches have targeted the postoperative period for rehabilitation and lifestyle changes . However , recent evidence shows that the preoperative period might be the optimal moment for intervention . This study will determine the impact of multimodal prehabilitation on patients ’ functional capacity and postoperative complications . Methods / design This international multicenter , prospect i ve , r and omized controlled trial will include 714 patients undergoing colorectal surgery for cancer . Patients will be allocated to the intervention group , which will receive 4 weeks of prehabilitation ( group 1 , prehab ) , or the control group , which will receive no prehabilitation ( group 2 , no prehab ) . Both groups will receive perioperative care in accordance with the enhanced recovery after surgery ( ERAS ) guidelines . The primary outcomes for measurement will be functional capacity ( as assessed using the six-minute walk test ( 6MWT ) ) and postoperative status determined with the Comprehensive Complication Index ( CCI ) . Secondary outcomes will include HRQoL , length of hospital stay ( LOS ) and a cost-effectiveness analysis . Discussion Multimodal prehabilitation is expected to enhance patients ’ functional capacity and to reduce postoperative complications . It may therefore result in increased survival and improved HRQoL. This is the first international multicenter study investigating multimodal prehabilitation for patients undergoing colorectal surgery for cancer . Trial registration Trial Registry : NTR5947 – date of registration : 1 August 2016 Objective : Investigation of the feasibility and preliminary effect of a short-term intensive preoperative exercise programme for elderly patients scheduled for elective abdominal oncological surgery . Design : Single-blind r and omized controlled pilot study . Setting : Ordinary hospital in the Netherl and s. Subjects : Forty-two elderly patients ( > 60 years ) . Interventions : Patients were r and omly assigned to receive a short-term intensive therapeutic exercise programme to improve muscle strength , aerobic capacity , and functional activities , given in the outpatient department ( intervention group ; n = 22 ) , or home-based exercise advice ( control group ; n=20 ) . Main measures : Parameters of feasibility , preoperative functional capacity and postoperative course . Results : The intensive training programme was feasible , with a high compliance and no adverse events . Respiratory muscle endurance increased in the preoperative period from 259 ± 273 to 404 ± 349 J in the intervention group and differed significantly from that in the control group ( 350 ± 299 to 305 ± 323 J ; P<0.01 ) . Timed-Up- and -Go , chair rise time , LASA Physical Activity Question naire , Physical Work Capacity and Quality of Life ( EORTC-C30 ) did not reveal significant differences between the two groups . There was no significant difference in postoperative complications and length of hospital stay between the two groups . Conclusion : The intensive therapeutic exercise programme was feasible and improved the respiratory function of patients due to undergo elective abdominal surgery compared with home-based exercise advice |
12,487 | 32,255,995 | There was inconsistent evidence across studies regarding the effectiveness of HA compared to other intra-articular injections .
The formulation of the administered viscosupplementation did not appear to influence outcomes .
Furthermore , rates of conversion to THA were relatively low when evaluating 1- to 4-year follow-up intervals .
Discussion Non-comparative studies consistently demonstrated that HA can achieve satisfactory pain reduction and functional improvement .
However , there was not enough evidence in the current literature regarding whether HA is superior to placebo or other types of intra-articular injections . | Introduction Osteoarthritis of the hip is one of the leading causes of disability worldwide .
There is lack of agreement among providers and governing agencies regarding the efficacy of hyaluronic acid ( HA ) for the management of hip osteoarthritis ( OA ) .
Therefore , the purpose of this systematic review was to determine how HA administration impacts 1 ) patient reported outcome measures ( PROMs ) and 2 ) rates of conversion to THA . | Purpose The aim of this study was to compare the clinical efficacy of ultrasound-guided intra-articular injections of autologous platelet rich plasma ( PRP ) versus hyaluronic acid ( HA ) for symptomatic early osteoarthritis ( OA ) of the hip . Methods A prospect i ve controlled double-blinded r and omized trial on 80 patients with hip OA was conducted . The patients were divided in two groups of 40 patients each : group 1 underwent three PRP intra-articular ultrasound-guided injections , whereas group 2 underwent three HA injections . WOMAC , VAS , and Harris Hip Score were evaluated for both groups before and at 6 and 12 months after treatment . Results The two groups were comparable in age , sex , body mass index , and severity of hip OA . Both groups showed a significant improvement from baseline at 6-month and 12-month follow-ups for all the outcome measures . No major complications were observed during the treatment and at follow-ups in both the groups . Conclusion PRP did not offer significantly better results compared with HA in patients with moderate signs of OA , and thus it should not be considered as first-line treatment . Level of Evidence Level II , r and omized controlled trial Introduction Comparison of intra-articular bacterial-derived hyaluronic acid ( Hyalubrix ® ) ( HA ) with local analgesia ( mepivacaine ) for osteoarthritis ( OA ) of the hip . Methods A pilot prospect i ve , double-blind , 6-month r and omized trial of 42 patients with hip OA . HA or mepivacaine was administered twice ( once a month ) under ultrasound guidance . Efficacy measurements included the Lequesne 's algofunctional index , a visual analog scale for pain , concomitant use of analgesia , patient and physician global measurement , and safety . Results Patients in the HA group exhibited a significantly reduced Lequesne 's algofunctional index 3 and 6 months after treatment ( P < 0.001 ) and significantly reduced visual analog scale pain scores 3 and 6 months after treatment ( P < 0.05 ) compared with the local anesthetic group . All primary and secondary measures were significantly improved versus baseline , but other than the above were not different from each other at 3 or 6 months . Adverse effects were minimal . Conclusions This comparative study suggests a beneficial effect and safety of intra-articular HA in the management of hip OA.Trial registration numberIS RCT N39397064 Background To identify predictive factors of response to viscosupplementation ( VS ) in patients with hip osteoarthritis ( HOA ) . Methods Prospect i ve , multicentre , open-label trial , achieved in daily practice conditions . Patients with HOA were treated with a single intra-articular injection of a cross-linked hyaluronic acid combined with mannitol ( HAnox-M-XL ) , using imaging guidance . WOMAC pain and function scores and patient global assessment ( PGA ) were assessed at baseline and day 90 . Improvement , satisfaction and efficacy were self-assessed at day 90.Hip radiographs at baseline were scored using Kellgren-Lawrence grade and Osteoarthritis Research Society International ( OARSI ) score . Associations between clinical and radiological features and response to VS ( pain improvement > 50 % at day 90 ) were assessed in univariate analysis , and then using logistic regression , adjusted for confounding factors . Results The intent-to-treat ( ITT ) population included 97 patients ( 57 females , mean age 63 ) . Ninety completed the follow-up and 80 had full clinical and radiological data . Response to VS was achieved in 47.8 % of patients . In univariate analysis , the only clinical outcome statistically and negatively related to response was PGA at baseline ( p = 0.047 ) . Radiologically , response to VS was negatively correlated with joint space narrowing ( JSN ) score ( JSN < 2 vs. JSN ≥ 2 , p = 0.01 ) and was related to the patterns of femoral head migration ( p = 0.008 ) . In multivariate analysis , only JSN grade ( p = 0.03 ) remained significantly related to a poor response . Conclusion This pilot study , which needs further confirmation by larger scale trials , suggests that radiological features might be of importance for the decision of VS in patients with HOA.Trial registration numberID RCB N ° 2013-A00165 - 40 . Registered 31 January 2013 OBJECTIVE Several studies on knee osteoarthritis suggest that the intra-articular administration of hyaluronic acid products may be a relevant option in the management of patients with persistent pain . The aim of this study is to report the data of efficacy of US-guided HyalOne ® /Hyalubrix ® 60 injections in a large population of patients with hip osteoarthritis , repeated at least 2 times per year for up to seven years . PATIENTS AND METHODS This is a prospect i ve , post-marketing , cohort study . Data were collected from the ANTIAGE registry . Values of Lequesne index , pain VAS , NSAIDs intake , global medical and patients assessment s were evaluated every six months from the baseline to the end of the follow-up , seven years later . The inclusion criteria were : age ≥18 years , symptomatic hip osteoarthritis of at least 1-year duration , and up to 84 months of follow-up . All the patients received hyaluronic acid injections at least every six months , using ultrasound guidance to ensure accurate placement . RESULTS 1022 patients were included in the study . The patients were categorized by age classes , gender , and body mass index ( BMI ) . All the groups show a statistically significant reduction at all time points compared to baseline values of Lequesne index , pain VAS , NSAIDs intake , global medical and patients assessment s. There are slight differences in the subgroups of overweighted , obese and over 70 years patients . CONCLUSIONS Our study supports the clinical efficacy and safety of HyalOne ® /Hyalubrix ® 60 in patients affected by osteoarthritis . This is the first study , reporting on a large cohort of patients in different categories with a long follow-up on seven years . The data confirm the proper use of ultrasound-guided viscosupplementation ( VS ) as background therapy in the management of hip osteoarthritis Background : Intra-articular hyaluronic acid ( HA ) injection is used in management of knee , h and and hip osteoarthritis . While HA injection is included in the list of evaluated therapies , its efficacy and optimum dosing still have no consensus . This study was conducted to explore the possibility of using single injection HA to increase patient convenience while maintaining the therapeutic efficacy . Methods : We present a prospect i ve , open label , non-blinded , r and omized controlled trial performed in accordance with guidelines in principles of good clinical practice . Block r and omization was done for patients to receive either single 5 ml GO-ON injection or the conventional three injections of 2.5 ml GO-ON at weekly interval . Baseline Western Ontario McMaster University Osteoarthritis ( WOMAC ) scores were evaluated and recorded . All subjects were re-evaluated at 3 months and the WOMAC score recorded again as primary end points . Data analyses were performed with IBM SPSS Statistics for Windows software ( version 21.0 , IBM Corp , Armonk , New York , USA ) . Results : In the cohort of 127 patients , 33 were males and 94 females . The mean age was 59.1 years ( st and ard deviation ( SD ) = 7.25 ) in single injection arm and 60.1 years ( SD = 7.72 ) in triple injection arm . The two groups were recorded to have no significant difference in age ( p = 0.46 ) and Kellgren – Lawrence radiological grade ( p = 0.694 ) . There was significant increase in the WOMAC scores from the baseline ( pre-injection ) to that recorded 3 months after injection ( p < 0.001 ) in patients of both groups . However , there was no statistically significant difference noticed in this clinical improvement between the two arms ( p = 0.889 ) . Conclusion : The study shows single 5 ml dose regime comparing well with conventional three doses of 2.5 ml of intra-articular GO-ON HA injected at weekly intervals and confirms good efficacy , tolerability and safety of single larger dose of GO-ON knee intra-articular injection OBJECTIVE To obtain prospect i ve data on feasibility and safety of intra-articular injections of hylan G-F20 in patients with symptomatic hip osteoarthritis ( OA ) . METHODS Fifty-seven patients with primary hip OA , Kellgren-Lawrence grade II-III , aged > or = 40 and walking pain 50 - 90 mm on a visual analogue scale ( VAS ) were enrolled in an open-label , multicentre pilot trial . Hylan G-F20 ( 2 ml ) was injected intra-articularly ( IA ) in the hip under fluoroscopy at D0 , and follow-up visits were performed at D7 - 30 - 60 - 90 . The possibility of a second injection at D30 - 60 or 90 was considered if the reported pain level was equivalent to baseline . Adverse events , walking pain ( VAS ) , WOMAC index , patient and physician 's global assessment were recorded at each visit . RESULTS Twenty-five patients 1 injection and 32 received 2 injections . Transient hip pain was reported following 10.1 % of injections , but no patient withdrew from the study because of this . Two mild synovial fluid aseptic effusions occurred after the first injection . No systemic device-related adverse event was reported . Walking pain decreased from 69.3 mm at entry to 39.5 mm at the end point ( p < 0.0001 ) . All other outcome measures decreased significantly . CONCLUSION Viscosupplementation with hylan G-F20 is feasible , easy to perform and well-tolerated in hip OA . A double-blind , controlled study should be performed to confirm data on its efficacy This paper aims to compare the results of single-joint knee vs hip hyaluronic acid ( HA ) injections in patients with osteoarthritis ( OA ) involving both the knee and hip joints . Thirty-eight patients who were diagnosed to have both hip and knee OA were enrolled . Patients were divided into two groups to receive HA injection three times at 1-week intervals either to the hip or knee joints . Pain level during activities and rest was measured by using visual analog scale ( VAS ) . Western Ontario and McMaster University Osteoarthritis Index ( WOMAC 5-point Likert 3.0 ) was also used prior to the injections and 1 month after the 3rd injection . In the knee injection group , the intragroup analysis revealed significant improvements in VAS activity pain , VAS rest pain , and WOMAC pain values following injection when compared with preinjection values , while no significant difference was detected in WOMAC stiffness , WOMAC physical function , and WOMAC total values . In the hip injection group , VAS activity pain , VAS rest pain , WOMAC pain , WOMAC stiffness , WOMAC physical function , and WOMAC total values showed significant improvement after the injection when compared with preinjection values . Although statistically not significant ( p > 0.05 ) , the comparison of the differences ( preinjection – postinjection ) between the groups demonstrated higher values in the hip injection group . We imply that intra-articular single-joint HA injections either to the knee or hip joints in OA patients with involvement of both of these joints are effective with regard to pain and functional status AIM To compare the efficacy of ultrasound-guided intra-articular ( IA ) treatment with platelet-rich plasma ( PRP ) versus viscosupplementation ( hyaluronic acid HA ) in hip osteoarthritis . METHODS : A total of 43 patients affected by monolateral severe hip osteoarthritis ( OA ) were included in the study . Patients were r and omized to receive either intra-articular PRP ( 3 ml ) or HA ( 30 mg/2 ml ; 1,000 - 2,900 kDa ) , 3 injections in total - 1/week . Clinical assessment s for each patient were made at baseline ( T0 ) , 4 ( T1 ) , and 16 weeks ( T2 ) of follow-up . The primary efficacy outcome was pain reduction as measured by VAS and by WOMAC pain subscale . RESULTS Data analysis revealed that , compared to T0 , in the PRP-treated group VAS scores significantly decreased at T1 but not at T2 , thereby indicating an early effect on pain which was not maintained at a longer term follow-up . In the HA group a significant decrease of both VAS and WOMAC values was registered only between T0 and T2 . CONCLUSIONS Intra-articular PRP had an immediate effect on pain that was not maintained at longer term follow-up when , on the contrary , the effects of intra-articular HA were evident INTRODUCTION Young adult hip osteoarthritis ( OA ) is a noteworthy problem , although rarer than the elderly form of the disease , causing limitations in social and working activities and prospect s. Treatment options are scarce and surgical procedures , frequently necessary , imply the major drawback of revising the prostheses periodically , whereas chronic nonsteroidal anti-inflammatory drugs ( NSAID ) consumption may provoke side effects . To explore alternative options to both surgery and long-term NSAID use , especially in the case of young patients , viscosupplementation seems to appear as an appropriate tool to relieve pain , ameliorate the function and delay surgery . AIM OF THE STUDY In this study we tackle the issue of the use of hyaluronic acid ( HA ) injections in young adults with symptomatic hip OA . RESULTS AND CONCLUSIONS These data , collected from 78 young patients , show that viscosupplementation is a safe procedure , and may provide significant relief from pain and functional recovery . Larger controlled studies are needed to establish otpimal treatment strategies and clinical factors predictive of treatment response Intra-articular injections of platelet-rich plasma ( PRP ) and hyaluronic acid ( HA ) represent efficacious medical treatments for osteoarthritis ( OA ) , although no comparative study on long-term efficacy in hip OA exists . The goals of the current study were to compare the clinical efficacy of PRP vs HA at 12 months of follow-up in patients with hip OA and evaluate the influence of the type of infiltration and patient age , sex , body mass index , and degree of OA on temporal clinical evolution . One hundred patients with chronic unilateral symptomatic hip OA were consecutively enrolled and r and omly assigned to 1 of 2 groups : group A received PRP and group B received HA administered via intra-articular ultrasound-guided injections . Patients were evaluated at baseline and after 1 , 3 , 6 , and 12 months using the Harris Hip Score ( HHS ) and visual analog scale ( VAS ) . An overall improvement was detected in both groups between 1- and 3-month follow-up . Despite a slightly progressive worsening between 6- and 12-month follow-up , the final clinical scores remained higher compared with baseline ( P<.0005 ) , with no significant differences between PRP and HA . Regarding clinical temporal evolution , multivariate analysis showed that HHS was not influenced by the type of infiltration , patient age , sex , body mass index , or degree of OA , whereas a significant association was detected between OA grade IV and VAS evolution ( P<.0005 ) . Intra-articular injections of PRP are efficacious in terms of functional improvement and pain reduction but are not superior to HA in patients with symptomatic hip OA at 12-month follow-up Hip osteoarthritis is very common and costly . The European League Against Rheumatology Committee agenda asks for research to investigate treatments able to slow down the progression of hip osteoarthritis ( OA ) , to delay joint replacement , and to determine the comparative effectiveness and cost-effectiveness of non-surgical and surgical treatment modalities as well as criteria relating to the indications for and timing of total hip replacement ( THR ) . After publishing the results of a r and omized controlled trial and a cohort study on the efficacy of Intra-articular sodium hyaluronate ( MW 1,500–2,000 kDa ) on symptomatic hip OA , we performed this retrospective study in patients suffering from hip OA treated with ultrasound-guided intra-articular injections of HyalOne ( Hyalubrix 60 Italian br and name ) involving a group of THR expert orthopedic surgeons to appraise whether or not considered eligible for THR and the frequency and timing of THR . Six orthopedists , not routinely performing hip intra-articular injections , each independently assessed whether 176 patients suffering from hip OA and treated with ultrasound-guided intra-articular injections of sodium hyaluronate ( MW 1,500–2,000 kDa ) were c and i date s for THR according to the clinical data ( age , body mass index , Pain Visual Analog Scale , Lequesne Algofunctional Index , global patient assessment , global physician assessment , nonsteroidal anti-inflammatory drug intake , and hip X-ray ) collected at the first intra-articular sodium hyaluronate injection visit and provided as anonymous electronic data . At 24 months , 159 out of 76 ( 90 % ) patients did not undergo to THR . At 48 months , 82 % ( N = 144 ) of the study population treated with intra-articular hyaluronic acid avoided THR . In the group of 93 patients considered c and i date s for THR ( that is , in which 4 , 5 , or 6 orthopedic surgeons agreed that the patient was a suitable c and i date for THR ) , only 17 had undergone THR , with survival results of 82 % at 24 months . At 48 months , this percentage reduced to 66 % in this group . In the other groups of patients ( in which respectively 3 , 2 , 1 or no surgeons were in agreement that the patient was a c and i date for THR ) arthroplasty is not recorded . Sodium hyaluronate ( MW 1,500–2,000 kDa ) given by ultrasound-guided injection seems to delay THR in the real context of actual overall management of symptomatic hip OA patients . Although further studies are necessary to confirm these data and to identify outcome predictors , hip viscosupplementation should be considered as conservative treatment to perform before proposing patients for THR Patients suffering from hip osteoarthritis ( OA ) are frequently symptomatic , and the disease can result in significant limitation of patients ’ activity and high social costs . Hip OA is generally managed with systemic treatments such as nonsteroidal anti-inflammatory drugs ( NSAIDs ) and /or symptomatic slow acting drugs . Viscosupplementation with hyaluronan ( HA ) or its derivatives , which aims to restore the physiological and rheological features of the synovial fluid to improve symptoms , is now a routinely prescribed treatment for OA of the knee . However , few data exist in the literature regarding the use of viscosupplementation in the treatment of hip OA . The objective of this prospect i ve , open , uncontrolled pilot study was to investigate the safety and effectiveness of intra-articular injection , under ultrasound control , of hylan G-F 20 for the treatment of OA of the hip . Twelve patients ( ≥40 years old ) with symptomatic hip OA were treated with one injection of 2 ml of hylan G-F 20 under ultrasound guidance . During the study , patients were evaluated for safety and efficacy using the Lequesne index , a visual analogue scale ( VAS ) measure of hip OA pain and analysis of NSAID consumption . Patients treated with hylan G-F 20 in this study showed clinical ly significant reductions in Lequesne and VAS scores and in the consumption of NSAIDs up to 3 months after the injection . In the 12 patients treated ( total of 14 injections ) , no systemic adverse events were observed . Three patients reported mild , local pain post-injection . This study demonstrates the potential of ultrasound-guided intra-articular injections of a viscosupplement into the hip joint and gives positive preliminary information about the safety and efficacy of hylan G-F 20 for the treatment of symptomatic hip OA Hip osteoarthritis ( OA ) is usually managed with systemic treatments such as nonsteroidal anti-inflammatory drugs ( NSAIDs ) and /or symptomatic slow-acting drugs . Unfortunately , many patients either can not tolerate NSAIDs or suffer serious , even fatal , NSAID-induced side effects , predominantly gastrointestinal ulceration and bleeding . Viscosupplementation , which aims to restore physiological and rheological features of the synovial fluid , is a well-accepted therapeutic option in knee OA patients , but limited data exist in the literature about its potential benefit for the treatment of hip OA . The purpose of this study is to observe the effects of hylan G-F 20 administered through ultrasound (US)-guided intra-articular ( IA ) injections in patients with symptomatic hip OA . We treated 30 patients with symptomatic hip OA . Under US guidance , 7 patients received one injection , 21 patients had two injections , and 2 patients received three injections , each with 2 ml of hylan G-F 20 . Lequesne index , VAS scale of hip pain , and NSAID consumption were evaluated at baseline as well as 2 and 6 months after the beginning of the treatment . No systemic adverse events were observed . Lequesne index , VAS pain score , and NSAID consumption showed a reduction that was statistically significant to the baseline . The present observation suggests the potentiality for the safety and efficacy of hylan G-F 20 injected under US guidance in patients with symptomatic hip OA . Further controlled studies are needed Purpose Osteoarthritis ( OA ) is the most common joint disorder in the elderly , causing significant pain which negatively affects mobility and quality of life . The aim of the study was to assess the effectiveness of ultrasound image-guided intra-articular injections of Hyalubrix ® combined with exercise therapy in the treatment of hip osteoarthritis . Methods This was a single site , prospect i ve , open-label , Investigator-initiated study . Forty patients were enrolled and received three ultrasound image-guided injections of Hyalubrix ® , 45 days apart , combined with three sessions a week of physical therapy ( proprioceptive rehabilitation of the lower limbs ; gait training ; balance training ) up to a total of 30 sessions ( 10 weeks ) , starting from one week after the first injection . Results The primary objective was to achieve a lasting reduction in OA symptoms related to pain during activity . During the course of the study the pain perceived by the patient during activity dropped from a mean value of 6.94 cm to a mean value of 1.46 cm and showed a statistically significant decrease from visit 1 compared to baseline ( p < 0.05 ) which was confirmed at all the subsequent time points . Significant improvements were also observed in the evaluation of the secondary objectives : hip disability ; OA-related pain at rest ; daily functioning and NSAIDs intake . Conclusions Results from this study including 40 patients for a total of 65 treated hips demonstrate a significant improvement in OA-related pain , hip disability , and patient 's daily functioning as well as a reduction in NSAIDs intake . Patients suffering from hip OA seem to benefit from the treatment with Hyalubrix ® injections plus exercise therapy We aim ed to compare the efficacy of intra-articular injections of a lower molecular weight hyaluronan ( LMW HA ) ( Ostenil ) with a higher molecular weight viscosupplement ( hylan G-F 20 , Synvisc ) in hip osteoarthritis . For this purpose , 43 patients ( 56 hips ) with hip osteoarthritis with a visual analogue scale ( VAS ) pain score higher than 50/100 , a Lequesne index greater than 6 , and persistence of the pain for longer than 3 months despite all conservative methods were enrolled in the study and r and omly assigned to two groups : 25 ( 32 hips ) received LMW HA and the remaining 18 patients ( 24 hips ) received hylan G-F 20 . Three injections were administered once weekly to each patient under fluoroscopic guidance . During the 6-month follow-up period , the primary outcomes were assessed at the 1st , 3rd , and 6th month by VAS , WOMAC ( Western Ontario and McMaster Universities Osteoarthritis Index ) , and Lequesne index . The intra-articular injections produced a significant reduction in VAS , WOMAC , and Lequesne index scores in both groups . After three injections , improvement was prominent at the 1st month and maintained for 6 months in both groups . The percentage reduction was 38 and 40 % ( p<0.001 ) in VAS pain score , 43 and 40 % in WOMAC ( p<0.001 ) , and 47 and 49 % in Lequesne index ( p<0.001 ) in the LMW HA and hylan G-F groups at the 6th month , respectively . However , there were no significant differences in outcomes between any of the measurements at the 1st , 3rd , and 6th month between the two groups ( p>0.05 ) . No systemic adverse effect was recorded . Local adverse effects consisting of pain and /or swelling were noted in 3 of 32 hips ( 9 % ) injected with LMW HA and in 3 of 24 hips ( 12.5 % ) injected with hylan G-F 20 . In conclusion , both types of viscosupplementation produced a significant clinical improvement during the 6-month follow-up period . However , no significant difference was found in outcomes between higher and lower molecular weight hyaluronan Abstract Background Viscosupplementation with hyaluronic acid ( HA ) is increasingly used for the treatment of hip osteoarthritis ( OA ) . The purpose of this study was to compare the efficacy of intra-articular injections of an ultra-high molecular weight viscosupplement ( UHMW-HA , Fermathron S ) with a medium molecular weight hyaluronan ( MMW-HA , Hyalubrix 60 ) in hip OA . Methods Fifty-four patients with hip OA grade 3 on the Kellgren/Lawrence scale were r and omized . All infiltrations were performed under ultrasound guidance . Evaluation was performed preoperatively and at 1 , 3 , 6 and 12 months after infiltration . Patients were clinical ly evaluated using Lequesne index , VAS and WOMAC score . Results Fifty patients , including 27 in the MMW-HA group and 23 in the UHMW-HA group , completed the follow-up . No significant difference was found between the two groups in terms of VAS , WOMAC or Lequesne index preoperatively or at 1 , 3 , 6 and 12 months after viscosupplementation . A stratified analysis was performed to study the development over time of Lequesne index of patients aged ≤ 55 years , > 55 and , ≤ 70 years and > 70 years and Lequesne index was different between the three age-stratified subgroups only in the MMW-HA group . The subgroup of older patients showed a higher Lequesne index than the subgroups of younger patients ( p < 0.05 ) . Conclusions UHMW-HA is a safe and effective treatment for hip osteoarthritis . A single dose of UHMW-HA was as effective as two doses of MMW-HA result ing in similar reductions of pain and disability . Study design Multicenter , independent , prospect i ve , r and omized controlled trial with level of evidence 1 Abstract Introduction : There is scarce data available on intra-articular hyaluronan ’s ability to modify the progression of osteoarthritis ( OA ) . Objective : The purpose of this retrospective pilot study was to assess the impact of treatment with hylan G-F 20 on progression to total hip replacement ( THR ) in patients with symptomatic hip OA . Research design and methods : The records of patients presenting with symptomatic hip OA and treated with hylan G-F 20 were analysed . Endpoints were the number of THRs performed and the survival time ( in months ) between commencement of treatment and THR , if performed . Endpoints were evaluated for the entire study population and for those sub-groups of patients which were , or were not , defined as c and i date s for THR prior to intra-articular treatment . Predictive factors of progression to THR were also assessed . Results : A total of 850 patients ’ records were evaluated and 224 patients ’ data were included in the study and evaluated . Eighty-four patients ( 37.5 % ) progressed to THR , 206 patients ( 92.0 % ) achieved 12 months survival , 170 patients ( 75.9 % ) achieved 24 months survival , and 69 patients ( 30.8 % ) achieved 5 years survival . Mean survival time was 36 months . Classification as a THR c and i date , Lequesne score , ultrasound pattern and the presence of diabetes were predictive factors for progression to THR . Conclusions : These results suggest that hylan G-F 20 could be included in the management of symptomatic hip OA before recommendation for THR , particularly in patients presenting with milder symptoms , or in patients where , due to comorbidities or personal choice , THR is not a feasible option . Limitations of this study include the retrospective study design and the lack of a control group to determine any placebo effect of hylan G-F 20 . Further prospect i ve studies are therefore needed to corroborate these results OBJECTIVE Hyaluronic acid ( HA ) and corticosteroids are both widely used for intra-articular treatment of knee osteoarthritis ( OA ) . We examined the effect of both drugs in intra-articular treatment for hip OA . METHODS One hundred and one patients with hip OA were included in a prospect i ve double blind study , using a r and omized controlled trial with a three-armed parallel-group design . Three ultrasound-guided , intra-articular injections were given at 14 days interval . The primary outcome measure was ' pain on walking ' , registered on a visual analogue scale ( VAS ) . Evaluation was performed at baseline and after 14 , 28 and 90 days . The study adhered to the Consoli date d St and ards of Reporting Trials . All analyses were based on intention-to-treat analyses , and used ' mixed- procedures ' with the baseline-observation as covariate . RESULTS There were no significant interactions with respect to Treatment x Time for any of the analyzed outcome measures . There was a significant treatment effect for ' pain on walking ' ( P=0.044 ) due to a significant improvement following corticosteroid compared to saline with an effect-size of 0.6 ( 95 % confidence interval : 0.1 - 1.1 , P=0.021 ) . By contrast , HA compared to saline had an effect size of 0.4 ( -0.1 to 0.9 ; P=0.13 ) . The peak-effect was obtained after 2 weeks . There was no difference between the treatment groups at endpoint . No significant side effects of the injections were observed . CONCLUSIONS Patients treated with corticosteroids experienced significant improvement during the 3 months of intervention , with an effect size indicating a moderate clinical effect . Although a similar significant result following treatment with HA could not be shown , the effect size indicated a small clinical improvement . A higher number of patients in future HA studies would serve to clarify this point Aim To evaluate , in daily clinical practice , the efficacy and tolerability of a single intra-articular injection of non-animal-stabilized hyaluronic acid ( NASHA ) in patients treated for symptomatic hip OA ( HOA ) . Methods St and ardized follow-up ( FU ) . Patients : forty patients suffering from HOA treated by a single intra-articular injection of NASHA in the painful hip under fluoroscopy . Evaluation : patient global assessment ( PGA ) and walking pain ( WP ) on a 100 mm visual analogue scale , WOMAC index , Lequesne index at each visit . Statistics : last observation carried forward . Treatment efficacy was assessed using OMERACT-OARSI response criteria , minimal clinical ly important improvement ( MCII ) , patient acceptable symptom state ( PASS ) obtained from PGA , WOMAC and WP . Predictive factors of efficacy were also studied . Results Efficacy evaluation : 34 patients were assessable ( mean FU 159 days ) . All clinical variables ( WP , PGA , WOMAC , Lequesne index ) decreased significantly between baseline and last evaluation . Twenty-two patients ( 71 % ) were classified OMERACT-OARSI responders , 25 subjects ( 75.8 % ) were classified PASS+ , and 19 ( 61.3 % ) fulfilled criteria for MCII . Out of clinical and radiological variables only Lequesne index ( p = 0.04 ) and WOMAC ( p = 0.04 ) at baseline were found to be predictive of treatment efficacy . Safety evaluation : the treatment was well tolerated . There were no severe adverse events related to the treatment or to the procedure . However 15 of the 28 assessable patients experienced transient increase of pain in the target hip during the first week after injection . Conclusion Viscosupplementation of the hip with NASHA is easily feasible in daily clinical practice , safe and well tolerated despite a frequent increase of pain the days following injection . Prospect i ve controlled trials are needed to confirm these data and to evaluate both safety and efficacy of a second course of treatment OBJECTIVE The aim of this study was to evaluate the accuracy and outcome of sonographically guided intra-articular sodium hyaluronate injections in patients with osteoarthritis of the hip . METHODS The prospect i ve study involved 10 patients who had the diagnosis of unilateral hip osteoarthritis . The mean age of the patients was 63.2 years ( range , 27 - 80 years ) . Depending on patient body weight , either a 3.5- to 5-MHz convex transducer or a 5- to 12-MHz linear transducer was used to examine each affected joint . Every subject received 3 injections of sodium hyaluronate , 1 per week for 3 consecutive weeks . With real-time sonographic monitoring , each joint was penetrated with a 20-gauge Chiba needle . Contrast medium was injected initially , and proper intra-articular placement was verified with computed tomography before the hyaluronate injection . Each patient 's outcome was assessed on the basis of visual analog scale results and Western Ontario and McMaster Universities osteoarthritis index findings that were recorded before the set of injections and 2 , 4 , and 6 months after the third injection . RESULTS Computed tomography confirmed accurate placement in all 30 injections in the study . The visual analog scale and the Western Ontario and McMaster Universities osteoarthritis index scores showed that 80 % of the patients had less pain in the joint at 6 months after the last injection . CONCLUSIONS Sonographically guided intra-articular injection of sodium hyaluronate for patients with hip osteoarthritis is easy to perform and is a safe , economical , and well-tolerated form of treatment . In contrast to fluoroscopic or computed tomographic guidance , the sonographic technique exposes neither the patient nor the physician to radiation OBJECTIVE To assess , using the OMERACT-OARSI criteria , the clinical response of patients presenting with symptomatic hip osteoarthritis ( OA ) to one intra-articular injection of hylan G-F 20 . METHODS Open-label , multi-centre , prospect i ve , pilot study . Fifty-six patients presenting with primary hip OA , Kellgren-Lawrence grade II-III , age > or = 40 , with walking pain measuring 50 - 90 mm on a 100 mm visual analogue scale ( VAS ) . Intra-articular injection of a single 2 ml dose of hylan G-F 20 into the hip joint under fluoroscopic guidance . A second injection could be administered at day ( D ) 30 , 60 or 90 if pain was unchanged or returned to baseline levels . EFFICACY CRITERIA : The outcome of the first injection in the intent-to-treat ( ITT ) population was analysed 90 days after the injection in those patients that received a single injection , and on the day of the second injection in those patients that required two injections , using OMERACT-OARSI responder criteria ( obtained from WOMAC A and C indices and the patient 's global evaluation ) and variation in walking pain on VAS . RESULTS The percentage of responders according to the OMERACT-OARSI response criteria was 53.6 % . An inverse correlation was observed between reduction in pain and joint space narrowing score ( P=0.03 ) . CONCLUSION In the absence of a control group , the efficacy of the treatment can not be determined conclusively . Nevertheless these data suggest that hylan G-F 20 is a symptomatic treatment of hip OA , particularly in less severe radiological cases . A double-blind , controlled study is required to confirm these data Background Intra-articular injection is effective for osteoarthritis , but the best single injection strategy is not known , nor are there established predictors of response . The objectives of this study were to assess and predict response to a single ultrasound-guided injection in moderate to severe hip osteoarthritis . Methods 77 hip osteoarthritis patients entered a prospect i ve , r and omised controlled trial , r and omised to one of four groups : st and ard care ( no injection ) ; normal saline ; non-animal stabilised hyaluronic acid ( durolane ) or methylprednisolone acetate ( depomedrone ) . Main Outcome Measures Numerical rating scale ( NRS 0–10 ) ‘ worst pain ’ , Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) pain/function . Potential predictors of response ( including radiographic severity , ultrasound synovitis and baseline symptom severity ) were examined using univariate logistic regression analysis and Fisher 's exact test . Results NRS pain , WOMAC pain and function improved significantly for the steroid arm alone . Effect sizes at week 1 were striking : NRS pain 1.5 , WOMAC pain 1.9 and WOMAC function 1.3 . Outcome Measures in Rheumatoid Arthritis Clinical Trials — Osteoarthritis Research Society responder criteria identified 22 responders ( intention-to-treat ) : steroid 14 ( 74 % ; number needed to treat , two ) ; saline , four ( 21 % ) ; durolane , two ( 11 % ) ; and no injection , two ( 10 % ; χ2 test between groups , p<0.001 ) . Corticosteroid arm response was maintained over 8 weeks ( summary measures analysis of variance , p<0.002 for NRS pain ) . Synovitis was a significant predictor of response at weeks 4 and 8 ( p<0.05 , Fisher 's exact test ; week 4 OR 16.7 , 95 % CI 1.4 to 204 ) . Conclusions Ultrasound-guided corticosteroid injections are highly efficacious ; furthermore synovitis on ultrasound is a biomarker of response to injection OBJECTIVES Hyaluronic acid ( HA ) is used for intraarticular treatment of hip osteoarthritis ( OA ) . The objective of this study was to determine the efficacy of intraarticular injection of HA through a lateral approach under fluoroscopic control for advanced hip OA . METHODS The study included 21 patients with advanced hip OA . All patients received 2.5 ml HA injection once a week for 3 weeks by lateral approach under fluoroscopic control . Disability ( Lequesne index ) , pain scores ( visual analog scale-VAS ) and analgesic use of patients were assessed before treatment and 1 , 3 and 6 months after the treatment . RESULTS Lequesne index and VAS pain scores measured 1 , 3 and 6 months after treatment were significantly lower compared to baseline scores ( p<0.001 ) . Although analgesic use was significantly reduced 1 and 3 months after treatment compared to baseline ( p<0.05 ) , no difference was determined in analgesic use at the 6th month ( p>0.05 ) . No side effect was observed . CONCLUSION In conclusion , intraarticular HA injection through a lateral approach under fluoroscopic control was shown to be a safe and effective method for patients with advanced hip OA OBJECTIVE To study the efficacy of hylan G-F 20 in the treatment of osteoarthritis ( OA ) of the hip joint . DESIGN Prospect i ve within-group study . SETTING Musculoskeletal rehabilitation clinic . PARTICIPANTS Twenty-two patients ( 25 hips ) with hip joint OA who had failed to find pain relief from conservative methods such as physical therapy , exercises , and steroid injections . Demographics included 14 men and 11 women ( mean age , 56.4y ) , 21 of whom had mild to moderate OA and 4 of whom had severe OA of the hips . INTERVENTION Each hip joint was injected with 2mL of hylan G-F 20 at 2 , 3 , and 4 weeks and fluoroscopic lavage with 100mL of normal saline at week 1 . All patients had st and ard hip exercise regimen after the injection . MAIN OUTCOME MEASURES American Academy of Orthopaedic Surgeons ( AAOS ) Lower Limb Core Scale score and visual numeric pain score . RESULTS At 1-year follow-up , the AAOS Lower Limb Core Scale score improved from a preinjection mean of 44.2 to a follow-up mean of 86.1 ( P<.05 ) . The mean visual numeric pain score improved from a preinjection mean of 8.7 ( range , 6.4 - 10 ) to a follow-up mean of 2.3 ( range , 0 - 7.2 ) . The overall success rate was 84 % . In patients with mild to moderate OA , the mean pain score decreased from a preinjection value of 7.8 to a follow-up value of 1.7 . The success rate was 90.5 % in that subgroup . In patients with severe OA , the mean pain score decreased from a preinjection value of 9.1 to a follow-up value of 3.8 . The success rate was 50 % in that subgroup . There were no complications related to the injection . CONCLUSION Use of hylan G-F 20 injection is a viable option for treatment of mild to moderate OA of the hip joint Objective The aim of this study was to determine the efficacy and safety of viscosupplementation applied to the hip joint with the lateral approach and ultrasound guidance and to show whether this can be an alternative treatment model in hip osteoarthritis ( OA ) . Methods We performed three hylan G-F injections each to 14 patients with hip OA . We evaluated visual analog score ( VAS ) , Lequesne hip OA severity index , 15-meter walking time before injections and 30 and 90 days after injections , and patient satisfaction . Results We established that after 30 respectively 90 days of treatment , VAS , Lequesne hip OA severity index , and 15-meter walking time were statistically significantly lower than before the treatment . This decrease continued after the 30th day . No side effects or complications were observed . Conclusions Viscosupplementation performed under ultrasound guidance with the lateral approach is an effective and safe method and can be an alternative treatment of hip OA Abstract We compared the efficacy and safety of intra-articular hylan G-F 20 with methylprednisolone acetate ( MPA ) for treating symptomatic Kellgren-Lawrence grade ( KLG ) 2 or 3 hip osteoarthritis in a prospect i ve , r and omized , multicenter , double-blind trial ( N = 313 ) . Two injections of hylan G-F 20 were administered 2 weeks apart ( n = 150 ) , or 1 injection of 40 mg MPA and 1 sham injection 2 weeks later ( n = 155 ) . The Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) ( total and subscale ) , clinician observations , and patient global assessment s were collected at baseline and at weeks 4 , 8 , 12 , 16 , 20 , and 26 ( intent-to-treat population was analyzed ; n = 305 ) . Responder rates were assessed by WOMAC domain A , and criteria were established by the Outcome Measures in Rheumatology Clinical Trials – Osteoarthritis Research Society International ( OMERACT-OARSI ) . At week 26 , WOMAC A improved by 16.6 mm for hylan G-F 20 versus 13.6 mm for MPA . Response rates were higher with hylan G-F 20 versus MPA in patients with more advanced disease ( KLG 3 ) and were similar between hylan G-F 20 and MPA in patients with less advanced disease ( KLG 2 ) . Adverse events were similar between groups and between patients with KLG 2 or 3 . Hylan G-F 20 provided clinical ly meaningful improvements in pain and function , comparable with those of MPA , with good safety and tolerability . Thus , we conclude it is an appropriate option for treating hip osteoarthritis OBJECTIVE To evaluate the efficacy and tolerability of a single intraarticular ( IA ) injection of hyaluronic acid ( HA ) for the treatment of hip osteoarthritis ( OA ) . METHODS A multicenter , r and omized , parallel-group , placebo-controlled trial was conducted over 3 months . Patients ( older than 30 years ) with symptomatic hip OA ( pain score of > 40 mm on a visual analog scale [ VAS ] ) and a Kellgren/Lawrence grade of 2 or 3 were r and omly assigned to receive 1 fluoroscopically guided IA injection of HA ( 2.5 ml ) or placebo ( 2.5 ml ) . Patients were followed up for 3 months . The main outcome measure was pain score on a VAS ( 100 mm ) at month 3 compared with baseline . Secondary outcome measures were the proportion of responders defined by Osteoarthritis Research Society International criteria ; Western Ontario and McMaster Universities Osteoarthritis Index subscores for pain , stiffness , and disability ; and patient and physician global assessment . R and omization was computer generated . HA and placebo preparations were placed in numbered identical containers , and syringes were covered with masking tape . Physicians assessing outcomes were blinded with regard to group assignment . RESULTS Eighty-five patients were r and omized to the HA group ( n = 42 ) or placebo group ( n = 43 ) . Baseline characteristics were similar between the 2 groups . At 3 months , the decrease in pain score did not differ between the HA and placebo groups in the intent-to-treat analysis ( mean + /- SD decrease 7.8 + /- 24.9 mm with HA versus 9.1 + /- 27.4 mm with placebo ; P = 0.98 ) . The responder rates were 33.3 % and 32.6 % in the HA and placebo groups , respectively ( P = 0.94 ) . Other secondary end points did not differ between the groups , nor did use of rescue medication or frequency of adverse events . CONCLUSION Our findings indicate that a single IA injection of HA is no more effective than placebo in treating the symptoms of hip OA UNLABELLED We studied the short-term safety and efficacy of intraarticular hylan G-F 20 ( Synvisc ) in patients with symptomatic hip osteoarthritis . METHODS In this open-label prospect i ve study , patients who had hip osteoarthritis with a visual analog pain scale score greaterthan 40/100 and a Lequesne index greater than 6 received one or two intra-articular injections of hylan G-F 20 under fluoroscopic guidance . The patients were evaluated once a month . A response was defined as a 50 % decrease in the Lequesne score after 1 month as compared to baseline . RESULTS Thirty injections were performed in 22 patients with a mean age of 54 years . The response rate was 50 % ( 11/22 ) after the first injection . Five of the 11 patients who failed to respond to the first injection received a second injection on day 30 ; two had a response , yielding a cumulative response rate of 13/22 . In the six patients followed up for more than 6 months , the improvement was sustained . Short-term safety was satisfactory , with a self-limited exacerbation of pain during the first few days in three patients but no infections or other side effects OBJECTIVE Hip osteoarthritis ( OA ) is difficult to treat . Steroid injections reduce pain with short duration . With widespread adoption of office-based , image-guided injections , hyaluronic acid is a potentially relevant therapy . In the largest clinical trial to- date , we compared safety/efficacy of a single , 6-mL image-guided injection of hylan G-F 20 to saline in painful hip OA . METHOD 357 patients were enrolled in a multicenter , double-blind , r and omized saline placebo- controlled trial . Subjects were ≥35 years of age , with painful ( Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]-A1:5.0 - 8.0 ; numeric rating scale [ NRS ] : 0 - 10 ) mild-to-moderate hip OA ( Kellgren-Lawrence grade II/III ) and minimal contralateral hip pain ( WOMAC-A1 < 4 ) . Outcome measures included " pain on walking " ( WOMAC-A1 and -A ) , Patient Global Self- Assessment ( PTGA ) , WOMAC-A1 responder rate ( + ≥2 points on NRS ) , and adverse events ( AEs ) over 26 weeks . RESULTS 357 patients ( hylan G-F 20 single:182 ; saline:175 ) were enrolled . Both groups demonstrated significant pain improvement from baseline over 26 weeks ( P < 0.0001 ) ; saline-induced pain reduction was a remarkable 35 % . WOMAC-A and PTGA scores also significantly improved ( P < 0.0001 ) . No statistically significant difference was observed between groups in WOMAC-A1 scores ( hylan G-F 20 single:-2.19 ± 0.16 ; saline:-2.26 ± 0.17 ) or WOMAC-A1 responders ( 41 - 52 % ) . Treatment-related AE rates at target hip were similar ( hylan G-F 20 single:23 patients [ 12.8 % ] ; saline:12 [ 7.0 % ] ) . Posthoc analysis found , despite protocol requirements , many patients had psychological ( 31 % ) or potential neuropathic pain ( 27.5 % ) conditions . CONCLUSION A single 6-mL hylan G-F 20 injection or saline for painful hip OA result ed in similar , statistically significant/ clinical ly relevant pain and function improvements up to 6 months following injection ; no differences between hylan G-F 20 and saline placebo were observed Background : Nonsurgical management of symptomatic hip osteoarthritis needs real-world evidence . We evaluated the effectiveness and tolerability of US-guided intra-articular treatment of two hyaluronic acids ( HAs ) commercially available in Italy and investigated predictors of response . Methods : Outpatient records including three cohorts : 122 subjects treated with medium ( 1,500–3,200 kDa ; Hyalubrix ® ) molecular weight ( MW ) or high ( hylan G-F20 ; Synvisc ® ) MW HAs and 20 controls taking NSAIDs/analgesics on dem and were retrospectively analyzed . Pain VAS score , WOMAC , NSAID/analgesic consumption , and causes of suspension were available at 1 , 6 , 12 , and 24 months after first administration . As selection bias usually affects observational retrospective studies , a quasi-r and omization process was attained by performing propensity score approach . Results : Propensity score adjustment successfully allowed comparisons among balanced groups of treatments . VAS and WOMAC considerably decreased over time in treated groups independently of the radiological grade ( p<0.001 ) . On the other h and , the control group showed only a slight and rather uneven variation in VAS . Mean score changes were comparable in both HA cohorts from the earliest stages ( ΔVAS(HA1,500–3,200kDa)T1vsT0 = −20 % ; ΔVAS(hylan G-F20)T1vsT0 = −23%/ΔWOMAC(HA1,500–3,200kDa)T1vsT0 = −17 % ; ΔWOMAC(hylan G-F20)T1vsT0 = −19 % ) , reaching a further substantial reduction after 12 months ( ΔVAS(HA1,500–3,200kDa)T12vsT0 = −52 % ; ΔVAS(hylan G-F20)T12vsT0 = −53%/ΔWOMAC(HA1,500–3,200kDa)T12vsT0 = −45 % ; and ΔWOMAC(hylan G-F20)T12vsT0 = −47 % ) . Almost 11 % ( = 13/122 ) of ineffectiveness and few moderate local side effects 3 % ( = 4/122 ) were detected . Conclusions : Viscosupplementation in a real-life setting seems to provide a sound alternative in pain management in comparison to oral NSAIDs/analgesics , guaranteeing a reduced intake of pain killer medications . Analgesic effectiveness , functional recovery , and reduced joint stiffness extend and improve over 12 and 24 months , suggesting that repeated administrations achieve an additive effect Background : The effectiveness of intra-articular platelet-rich plasma ( PRP ) injections has been evaluated in knee chondroplasty and osteoarthritis ( OA ) ; however , little evidence of its efficacy in hip OA exists . Purpose : To compare the therapeutic efficacy of autologous PRP , hyaluronic acid ( HA ) , or a combination of both ( PRP+HA ) in hip OA . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Patients aged between 18 and 65 years who were treated with outpatient surgery and who had hip OA and pain intensity at baseline of > 20 on a 100-mm visual analog scale ( VAS ) were recruited for this study . Exclusion criteria were extensive surgery ; presence of excessive deformities ; or rheumatic , infective , cardiovascular , or immune system disorders . The primary outcome measure was a change in pain intensity as assessed by the VAS at 2 , 6 , and 12 months after treatment . Secondary outcome measures were the Harris Hip Score , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , and concentration of growth factors in PRP and their correlation with clinical outcomes . Clinical outcomes were evaluated by assessors and collectors blinded to the type of treatment administered . Results : A total of 111 patients were r and omly assigned to 3 groups and received 3 weekly injections of either PRP ( 44 patients ) , PRP+HA ( 31 patients ) , or HA ( 36 patients ) . At all follow-ups , the PRP group had the lowest VAS scores . In particular , at 6-month follow-up , the mean VAS score was 21 ( 95 % CI , 15 - 28 ) in the PRP group , 35 ( 95 % CI , 26 - 45 ) in the PRP+HA group , and 44 ( 95 % CI , 36 - 52 ) in the HA group ( P < .0005 [ PRP vs HA ] and P = .007 [ PRP vs PRP+HA ] ; F = 0.663 ) . The WOMAC score of the PRP group was significantly better at 2-month follow-up ( mean , 73 ; 95 % CI , 68 - 78 ) and 6-month follow-up ( mean , 72 ; 95 % CI , 67 - 76 ) but not at 12-month follow-up . A significant , “ moderate ” correlation was found between interleukin-10 and variations of the VAS score ( r = 0.392 ; P = .040 ) . Significant improvements were achieved in reducing pain and ameliorating quality of life and functional recovery . Conclusion : Results indicated that intra-articular PRP injections offer a significant clinical improvement in patients with hip OA without relevant side effects . The benefit was significantly more stable up to 12 months as compared with the other tested treatments . The addition of PRP+HA did not lead to a significant improvement in pain symptoms |
12,488 | 24,625,083 | The results point to significant challenges to the implementation of patient decision support using this model , including indifference on the part of health care professionals .
This indifference stemmed from a reported lack of confidence in the content of decision support interventions and concern about disruption to established workflows , ultimately contributing to organizational inertia regarding their adoption .
Conclusions It seems too early to make firm recommendations about how best to implement patient decision support into routine practice because approaches that use a ‘ referral model ’ consistently report difficulties . | Background Two decades of research has established the positive effect of using patient-targeted decision support interventions : patients gain knowledge , greater underst and ing of probabilities and increased confidence in decisions .
Yet , despite their efficacy , the effectiveness of these decision support interventions in routine practice has yet to be established ; widespread adoption has not occurred . | OBJECTIVE To develop and vali date the Readiness for Implementation Model ( RIM ) . This model predicts a healthcare organization 's potential for success in implementing an interactive health communication system ( IHCS ) . The model consists of seven weighted factors , with each factor containing five to seven elements . DESIGN Two decision-analytic approaches , self-explicated and conjoint analysis , were used to measure the weights of the RIM with a sample of 410 experts . The RIM model with weights was then vali date d in a prospect i ve study of 25 IHCS implementation cases . MEASUREMENTS Orthogonal main effects design was used to develop 700 conjoint- analysis profiles , which varied on seven factors . Each of the 410 experts rated the importance and desirability of the factors and their levels , as well as a set of 10 different profiles . For the prospect i ve 25-case validation , three time-repeated measures of the RIM scores were collected for comparison with the implementation outcomes . RESULTS Two of the seven factors , ' organizational motivation ' and ' meeting user needs , ' were found to be most important in predicting implementation readiness . No statistically significant difference was found in the predictive validity of the two approaches ( self-explicated and conjoint analysis ) . The RIM was a better predictor for the 1-year implementation outcome than the half-year outcome . LIMITATIONS The expert sample , the order of the survey tasks , the additive model , and basing the RIM cut-off score on experience are possible limitations of the study . CONCLUSION The RIM needs to be empirically evaluated in institutions adopting IHCS and sustaining the system in the long term Abstract Objective : To examine the use of evidence based leaflets on informed choice in maternity services . Design : Non-participant observation of 886 antenatal consultations . 383 in depth interviews with women using maternity services and health professionals providing antenatal care . Setting : Women 's homes ; antenatal and ultrasound clinics in 13 maternity units in Wales . Participants : Childbearing women and health professionals who provide antenatal care . Intervention : Provision of 10 pairs of Informed Choice leaflets for service users and staff and a training session in their use . Main outcome measures : Participants ' views and commonly observed responses during consultations and interviews . Results : Health professionals were positive about the leaflets and their potential to assist women in making informed choices , but competing dem and s within the clinical environment undermined their effective use . Time pressures limited discussion , and choice was often not available in practice . A widespread belief that technological intervention would be viewed positively in the event of litigation reinforced notions of “ right ” and “ wrong ” choices rather than “ informed ” choices . Hierarchical power structures result ed in obstetricians defining the norms of clinical practice and hence which choices were possible . Women 's trust in health professionals ensured their compliance with professionally defined choices , and only rarely were they observed asking questions or making alternative requests . Midwives rarely discussed the contents of the leaflets or distinguished them from other literature related to pregnancy . The visibility and potential of the leaflets as evidence based decision aids was thus greatly reduced . Conclusions : The way in which the leaflets were disseminated affected promotion of informed choice in maternity care . The culture into which the leaflets were introduced supported existing normative patterns of care and this ensured informed compliance rather than informed choice . What is already known on this topic Informed Choice leaflets are widely used in maternity care but little is known about their ability to influence informed choice and decision making High quality information is essential for promoting informed choice but is insufficient by itself What this study adds Time constraints and other pressures on health professionals result ed in a lack of discussion of the content of the leaflets Fear of litigation , power hierarchies , and the technological imperative in maternity care limited the choices available Health professionals promoted normative practice s rather than choice , and as women valued their opinions this led to the promotion of informed compliance rather than informed Objectives To describe the development , validation and inter-rater reliability of an instrument to measure the quality of patient decision support technologies ( decision aids ) . Design Scale development study , involving construct , item and scale development , validation and reliability testing . Setting There has been increasing use of decision support technologies – adjuncts to the discussion s clinicians have with patients about difficult decisions . A global interest in developing these interventions exists among both for-profit and not-for-profit organisations . It is therefore essential to have internationally accepted st and ards to assess the quality of their development , process , content , potential bias and method of field testing and evaluation . Methods Scale development study , involving construct , item and scale development , validation and reliability testing . Participants Twenty-five research er-members of the International Patient Decision Aid St and ards Collaboration worked together to develop the instrument ( IPDASi ) . In the fourth Stage ( reliability study ) , eight raters assessed thirty r and omly selected decision support technologies . Results IPDASi measures quality in 10 dimensions , using 47 items , and provides an overall quality score ( scaled from 0 to 100 ) for each intervention . Overall IPDASi scores ranged from 33 to 82 across the decision support technologies sample d ( n = 30 ) , enabling discrimination . The inter-rater intraclass correlation for the overall quality score was 0.80 . Correlations of dimension scores with the overall score were all positive ( 0.31 to 0.68 ) . Cronbach 's alpha values for the 8 raters ranged from 0.72 to 0.93 . Cronbach 's alphas based on the dimension means ranged from 0.50 to 0.81 , indicating that the dimensions , although well correlated , measure different aspects of decision support technology quality . A short version ( 19 items ) was also developed that had very similar mean scores to IPDASi and high correlation between short score and overall score 0.87 ( CI 0.79 to 0.92 ) . Conclusions This work demonstrates that IPDASi has the ability to assess the quality of decision support technologies . The existing IPDASi provides an assessment of the quality of a DST 's components and will be used as a tool to provide formative advice to DSTs developers and summative assessment s for those who want to compare their tools against an existing benchmark Background Decision aids are evidence based tools that assist patients in making informed values-based choices and supplement the patient-clinician interaction . While there is evidence to show that decision aids improve key indicators of patients ' decision quality , relatively little is known about physicians ' acceptance of decision aids or factors that influence their decision to use them . The purpose of this study was to describe physicians ' perceptions of three decision aids , their expressed intent to use them , and their subsequent use of them . Methods We conducted a cross-sectional survey of r and om sample s of Canadian respirologists , family physicians , and geriatricians . Three decision aids representing a range of health decisions were evaluated . The survey elicited physicians ' opinions on the characteristics of the decision aid and their willingness to use it . Physicians who indicated a strong likelihood of using the decision aid were contacted three months later regarding their actual use of the decision aid . Results Of the 580 eligible physicians , 47 % ( n = 270 ) returned completed question naires . More than 85 % of the respondents felt the decision aid was well developed and that it presented the essential information for decision making in an underst and able , balanced , and unbiased manner . A majority of respondents ( > 80 % ) also felt that the decision aid would guide patients in a logical way , preparing them to participate in decision making and to reach a decision . Fewer physicians ( < 60 % ) felt the decision aid would improve the quality of patient visits or be easily implemented into practice and very few ( 27 % ) felt that the decision aid would save time . Physicians ' intentions to use the decision aid were related to their comfort with offering it to patients , the decision aid topic , and the perceived ease of implementing it into practice . While 54 % of the surveyed physicians indicated they would use the decision aid , less than a third followed through with this intention . Conclusion Despite strong support for the format , content , and quality of patient decision aids , and physicians ' stated intentions to adopt them into clinical practice , most did not use them within three months of completing the survey . There is a wide gap between intention and behaviour . Further research is required to study the determinants of this intention-behaviour gap and to develop interventions aim ed at barriers to physicians ' use of decision aids We evaluated the effect of an intervention on call centre nurses ' knowledge of decision support and skills in coaching callers facing value-sensitive health decisions . Forty-one registered nurses at a health call centre were r and omly assigned to an intervention or control group . The intervention was a coaching protocol , online tutorial , skills building workshop and performance feedback . The main outcome measures were : knowledge test ; blinded quality assessment of coaching skills during simulated calls and call duration . Compared with controls , nurses in the intervention group had better knowledge ( 74 versus 60 % , P = 0.007 ) and decision coaching skills ( 81 versus 44 % , P < 0.001 ) , particularly in assessing decisional needs ( information , values clarity , support , stage and timing of decision ) and addressing support issues . Call duration did not differ ( 18.5 versus 16.7 min , P = 0.73 ) . The coaching protocol was rated as compatible with nurses ' views on decision-making and more advantageous compared with their usual practice s. The intervention improved the quality of nurses ' decision coaching without affecting call duration OBJECTIVE To assess the impact of a decision aid on perceived risk of heart attacks and medication adherence among urban primary care patients with diabetes . METHODS We r and omly allocated 150 patients with diabetes to participate in a usual primary care visit either with or without the Statin Choice tool . Participants completed a question naire at baseline and telephone follow-up at 3 and 6 months . RESULTS Intervention patients were more likely to accurately perceive their underlying risk for a heart attack without taking a statin ( OR : 1.9 , CI : 1.0 - 3.8 ) and with taking a statin ( OR : 1.4 , CI : 0.7 - 2.8 ) ; a decline in risk overestimation among patients receiving the decision aid accounts for this finding . There was no difference in statin adherence at 3 or 6 months . CONCLUSION A decision aid about using statins to reduce coronary risk among patients with diabetes improved risk communication , beliefs , and decisional conflict , but did not improve adherence to statins . PRACTICE IMPLICATION S Decision aid enhanced communication about the risks and benefits of statins improved patient risk perceptions but did not alter adherence among patients with diabetes OBJECTIVE Compliance with antipsychotic medication is a major issue in schizophrenia treatment , and noncompliance with antipsychotic treatment is closely related to relapse and rehospitalization . An enhanced involvement of patients with schizophrenia in treatment decisions ( " shared decision making " ) is expected to improve long-term compliance and reduce rehospitalizations . The aim of the present analysis was to study whether shared decision making ( SDM ) in antipsychotic drug choice would influence long-term outcome . METHOD From February 2003 to January 2004 , psychiatric state hospital in patients with a diagnosis of schizophrenia ( ICD-10 ; N = 107 ) were recruited for the trial using a cluster-r and omized controlled design . An SDM program on antipsychotic drug choice consisting of a decision aid and a planning talk between patient and physician was compared with routine care with respect to long-term compliance and rehospitalizations ( 6-month and 18-month follow-up ) . RESULTS On the whole , we found high rates of noncompliance and rehospitalization . There were no differences between intervention and control groups in the univariate analyses . However , when controlling for confounding factors in a multivariate analysis , there was a positive trend ( p = .08 ) that patients in the SDM intervention had fewer rehospitalizations . Additionally , a higher desire of the patient for autonomy and better knowledge at discharge were associated with higher hospitalization rates . CONCLUSION The intervention studied showed a positive trend but no clear beneficial effect on long-term outcomes . A more thorough implementation of SDM ( e.g. , iterative administration of decision aid ) might yield larger effects . Those patients with higher participation preferences are at higher risk for poor treatment outcomes and therefore require special attention . Strategies to match these patients ' needs might improve compliance and long-term outcomes Background . R and omized controlled trials show that patient decision aids ( DAs ) can promote shared decision making and improve decision quality . Despite this evidence , integration of DAs into routine clinical practice has proceeded slowly . Objective . To identify factors that promote or impede integrating DAs into clinical practice in a large health care delivery system . Design . Mixed- methods case study . Setting and Patients . Group Health , an integrated health plan and care delivery system in Washington state . Intervention . The project was carried out in 6 specialty service lines using 12 video-based DAs for preference-sensitive conditions related to elective surgical procedures . Measurements . Process data , site visits , meeting observations , and in-depth interviews conducted with clinical staff , project staff , and health plan leaders in 2009 and 2010 . Results . The project established systemwide and clinic-specific processes that facilitated the distribution of approximately 10,000 DAs over 2 years . Several factors were identified as important for success in this implementation , including strong support from senior leaders , establishing a system for previsit ordering and providing timely feedback to teams about distribution rates , engaging providers and staff in development of the implementation process , and finding ways to address concerns about conditions that were perceived as life-threatening and /or time sensitive . Limitations . Limitations included lack of data on patient perspectives , an implementation setting with salaried providers , and frontline provider interviews conducted in only selected service lines . Conclusions . With strong leadership , financial support , and a well-defined implementation strategy , 12 video-based DAs in 6 specialty service lines were integrated into routine practice over 2 years . Findings from this demonstration may advance the ability of other organizations to use DAs effectively and promote widespread adoption of shared decision making in routine patient care Decision aids ( DAs ) are tools to support patients make informed health decisions with their practitioner . They aim to improve patient knowledge of options , incorporate patient preferences and values , and increase patient involvement in health decision making . Increasingly , the debate about DAs concerns how they should be implemented in practice , with the view that DAs are superior to usual clinical care in facilitating health decisions . The authors challenge this view and suggest that DA research has focused on measures of decision process , leaving the effects on the outcome of the decision relatively unknown . It is still unclear in which conditions DAs are better for patient health and well-being than clinician-led decisions . The authors present a new r and omized design to examine the effects of DA-supported patient choice on patient-centered outcomes to identify where DAs are best implemented in clinical practice . In this design , patients are r and omized to 1 of 4 arms : intervention A , intervention B , choice of either intervention supported by a clinician , or choice of either intervention supported by a decision aid . Health and quality of life measured over the long term are presented as the primary outcomes . The authors propose that this design will allow the proper assessment of different modes of decision making BACKGROUND Shared decision-making ( SDM ) between professionals and patients is increasingly advocated from ethical principles . Some data are accruing about the effects of such approaches on health or other patient-based outcomes . These effects often vary substantially between studies . OBJECTIVE Our aim was to evaluate the effects of training GPs in SDM , and the use of simple risk communication aids in general practice , on patient-based outcomes . METHODS A cluster r and omized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practice s in Gwent , South Wales . A total of 747 patients with known atrial fibrillation , prostatism , menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments . After baseline , participating doctors were r and omized to receive training in ( i ) SDM skills ; or ( ii ) the use of simple risk communication aids , using simulated patients . The alternative training was then provided for the final study phase . Patients were r and omly allocated to a consultation during baseline or intervention 1 ( SDM or risk communication aids ) or intervention 2 phases . A r and omly selected half of the consultations took place in ' research clinics ' to evaluate the effects of more time for consultations , compared with usual surgery time . Patient-based outcomes were assessed at exit from consultation and 1 month follow-up . These were : COMRADE instrument ( principal measures ; subscales of risk communication and confidence in decision ) , and a range of secondary measures ( anxiety , patient enablement , intention to adhere to chosen treatment , satisfaction with decision , support in decision making and SF-12 health status measure ) . Multilevel modelling was carried out with outcome score as the dependent variable , and follow-up point ( i.e. exit or 1 month later for each patient ) , patient and doctor levels of explanatory variables . RESULTS No statistically significant changes in patient-based outcomes due to the training interventions were found : COMRADE risk communication score increased 0.7 [ 95 % confidence interval ( CI ) -0.92 to 2.32 ] after risk communication training and 0.9 ( 95 % CI -0.89 to 2.35 ) after SDM training ; and COMRADE satisfaction with communication score increased by 1.0 ( 95 % CI -1.1 to 3.1 ) after risk communication , and decreased by 0.6 ( 95 % CI 2.7 to -1.5 ) after SDM training . Patients ' confidence in the decision ( 2.1 increase , 95 % CI 0.7 - 3.5 , P < 0.01 ) and expectation to adhere to chosen treatments ( 0.7 increase , 95 % CI 0.04 - 1.36 , P < 0.05 ) were significantly greater among patients seen in the research clinics ( when more time was available ) compared with usual surgery time . Most outcomes deteriorated between exit and 1 month later . There was no interaction between intervention effects . CONCLUSION Patients can be more involved in treatment decisions , and risks and benefits of treatment options can be explained in more detail , without adversely affecting patient-based outcomes . SDM and risk communication may be advocated from values and ethical principles even without evidence of health gain or improvement in patient-based outcomes , but the re sources required to enhance these professional skills must also be taken into consideration . These data also indicate the benefits of extra consultation time |
12,489 | 26,472,544 | Conclusions Breast milk has a faster GE than formula milk . | Background The choice of infant formula is thought to play an important role on gastric emptying ( GE ) in a variety of gastrointestinal disorders .
It is known that many ingredients impact on GE , including the type of protein and level of hydrolysis .
In clinical practice , feeds are often recommended due to putative improved GE related to the type of protein and level of hydrolysis , however whether this is scientifically justified still needs to be established .
A systematic review comparing the impact of protein type and hydrolysis on GE in children was therefore performed . | BACKGROUND About 20 % of infants fed with breast-milk substitutes suffer from Gastro Esophageal Reflux ( GER ) and 1/3 of them also show Cow 's Milk Allergy ( CMA ) symptoms . METHODS We planned this study to assess by dynamic echography the usefulness of an Extensively Hydrolysed Cow 's Milk Formula ( eHF ) in infants suffering from GER . Ten infants showing GER symptoms and 10 normal babies , all fed with breast-milk substitutes , were enrolled . Clinical symptom scores related to GER were assessed for one week . The Gastric Emptying Time ( GET ) was determined by means of dynamic echography after feeding with cow 's milk-derived formulae and again after a week feeding with eHF in subjects previously showing GER symptoms . RESULTS All infants with a clinical diagnosis for GER showed an abnormally high average GET in comparison to normal subjects ( 205 vs 124 min , p = 0.000 ) . Switching to the eHF led to a significant clinical improvement ( p = 0.0039 ) especially in babies skin-test and RAST positive to cow 's milk , and to a significant decrease toward the normal value of the GET ( 167 min , p < 0.001 ) . CONCLUSIONS The eHF tested improves GER symptoms in infants suffering from this disease . Our experience confirms and supports the use of dynamic echography as a reliable , simple , and non-invasive diagnostic method for infants with an increased GET associated with clinical symptoms of GER ABSTRACT : Casein-predominant infant milk formulas have been speculated to predispose to lactobezoar formation in preterm infants due to delayed gastric emptying . There have been , however , no prospect i ve studies to prove this possi-bility . In a r and omized , double-blinded , prospect i ve study , we tested the hypothesis that preterm infants fed casein-predominant milk formula have slower gastric emptying than infants fed whey-predominant formulas . Twenty pre-term infants within the first 4 d of life were r and omized to receive either the whey-predominant formula Similac Special Care ( whey : casein ratio 60:40 ) or an experimental casein-predominant formula ( whey : casein ratio 18:82 ) . Only the protein composition differed between the two formulas . The infants were fed the assigned study formula until they reached approximately 2200 g body weight when a gastric emptying scan was performed , using the design ated study formula mixed with 25 μCi of technetium-99 sulfur colloid . Gastric emptying was followed continuously for 2 h. Gastric emptying at 30 , 60 , 90 , and 120 min was similar between the two study groups . The time for 50 % gastric emptying was 64.9 ± 12.3 min for the infants fed the whey-predominant formula and 56.5 ± 14.8 min for those fed the casein-predominant formula ( p = 0.75 ) . We conclude that the rate of gastric emptying in preterm infants fed casein-predominant formulas is similar to that in those fed whey-predominant formulas BACKGROUND & AIMS Gastric emptying ( GE ) is influenced by the type of nutrition . The objective of this study was to compare GE in infants fed an intact protein formula ( IPF ) , a partially hydrolysed formula ( PHF ) , and an extensively hydrolysed formula ( EHF ) . METHODS This was a double-blind , r and omized , cross-over study . Following a fasting period of > or = 3 h , 20 healthy newborns were fed IPF , PHF , and EHF containing 50 microl (13)C-octanoic acid ( OA ) . Breath sample s were taken before feeding and every 15 min for 4 h thereafter . (13)C-OA breath test was assessed by isotope-ratio mass spectrometry , and GE half-times ( t(1/2 ) ) were determined . RESULTS Seventeen infants with a mean gestational age of 37 wk ( range 28 - 40 wk ) and birth weight of 2698 g ( range 720 - 3690 g ) completed the study . At study initiation , the mean age was 31 d ( range 6 d-13 wk ) and the mean weight was 3466 g ( range 2100 - 5700 g ) . EHF emptied significantly faster than IPF and PHF ( medians 46 vs. 55 and 53 min , respectively , Wilcoxon , P<0.05 for both ) . There was no significant difference between GE of PHF and IPF ( Wilcoxon , P=0.2 ) . CONCLUSIONS EHF may be better tolerated by infants with GE problems Summary The role of delayed gastric emptying ( GE ) in the pathogenesis of gastroesophageal reflux ( GER ) in infants is controversial at present . GE has been shown to be altered by the composition and osmolality of the feedings . This prospect i ve study was undertaken to assess the changes in the GE and the percentage of time GER was detected by scintigraphy using three different formulas on consecutive days in infants with GER . Twenty-eight infants under 1 year of age diagnosed to have GER by extended intraesophageal pH monitoring ( pH being < 4.0 for > 5 % of the duration of the test ) , underwent scintigraphy on three consecutive days using the same volume per single feeding of a casein-predominant , soy , or a wheyhydrolysate formula in a r and omized order . The formulas were isocaloric . Gastric emptying and percentage of GER into the esophagus were estimated for 60 min following these feedings . Mean GER percent during the study was 20.39 , 17.68 , and 16.34 on casein-predominant , soy , and whey-hydrolysate formulas , respectively , and was not significantly different . Mean values of GE were 39.7 % , 44.6 % , and 48.5 % on casein , soy , and whey formula , respectively . No significant difference in GE was also observed between casein-predominant and soy formula . However , a significant difference was observed ( p < 0.05 ) on GE between casein-predominant and whey-hydrolysate feedings . Our data suggest that formula selection may be important in the treatment of conditions associated with delayed gastric emptying The present study was design ed to determine the effects of milk composition and the influence of gastro-oesophageal reflux ( GOR ) on gastric emptying . Cineoesogastrocintigraphy ( COGS ) was performed in 201 infants between 0 - 1 year of age in order to detect GOR , and provided a means of estimation of the gastric emptying ( GE ) . Ninety infants appeared free from GOR and constituted the control group ; 111 had GOR . There infants were fed human milk or various st and ard formulae . In addition , 20 infants fed a whey-hydrolysate formula were tested . An appropriate volume of milk was marked with sulfur-colloid Tc ( 200 microcuries ) . Measurements of gastric radioactivity were made 30 min and 120 min after ingestion . For the whole population , the infants with GOR had slightly more rapid GE after 30 min ( P less than 0.05 ) , but , for the same type of milk , there was no significant difference between GOR and controls . GE did not differ with age or sex , but differed mainly according to the type of milk . In the control group , gastric residual content ( GRC ) at 120 min was 18 + /- 11 per cent with human milk ( n = 7 ) , 16 + /- 21 per cent with whey-hydrolysate formula ( n = 8) , 25 + /- 17 per cent with acidified formula ( n = 13 ) , 26 + /- 19 per cent with whey-predominant formula ( n = 22 ) , 39 + /- 17 per cent with casein-predominant formulae ( n = 20 ) , 47 + /- 19 per cent with follow-up formulae ( n = 16 ) and 55 + /- 19 per cent with cow 's milk ( n = 12 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND & AIM Dysmotility , nausea and vomiting are common among children with cerebral palsy . This study aim ed to evaluate influence of protein composition on rate of gastric emptying and study the relation between gastric emptying and postpr and ial gastrointestinal symptoms . METHODS 15 children with cerebral palsy , using gastrostomy , received four liquid test meals on separate days in r and om order . The meals contained a st and ard carbohydrate and fat base plus one of four protein modules ( 100 % casein ( A ) , hydrolysed whey ( B ) , amino acids ( C ) and 40 % casein/60 % whey ( D ) ) with a total energy of 1 kcal/ml . The (13)C octanoic acid breath test was applied to assess gastric emptying . RESULTS When comparing half emptying time ( T(1/2 ) ) of the fast emptying meals ( meal B , C and D ) with the slowest emptying meal ( meal A ) , more rapid emptying was demonstrated for meal D ( p < 0.001 ) . For meal D , emptying was significantly faster in children with postpr and ial symptoms than in those without ( p < 0.01 ) . CONCLUSION In children with cerebral palsy using gastrostomy , gastric emptying is influenced by type of protein in the meal . The present results also suggest that there is a relation between rapid gastric emptying and postpr and ial gastrointestinal symptoms . CLINICAL TRIALS.GOV : UUSKBK 28200706 BACKGROUND & AIMS The aim was to study the influence of Nissen fundoplication on rate of gastric emptying and postpr and ial symptoms in relation to protein source in liquid meals in children with cerebral palsy . METHODS Ten children with cerebral palsy and Nissen fundoplication and ten with cerebral palsy without Nissen fundoplication were studied . Patients had gastrostomy and received two meals , double-blinded , in r and om order , on separate days . Meals contained a st and ardised carbohydrate and fat base plus one of two protein modules ( Meal A : 100 % casein ; Meal B : 40 % casein/60 % whey ) . The (13)C octanoic acid breath test was used to assess gastric emptying . Postpr and ial symptoms were recorded . Results are given as median . RESULTS For meal A and B , respectively , time until 50 % of the meal had emptied ( T1/2 ) was 110 in the Nissen fundoplication- and 181 min in the non-Nissen fundoplication group , ( p = 0.35 ) and 50 and 85 min ( p = 0.25 ) . Seven in the Nissen fundoplication group reported postpr and ial symptoms to meal B , none in the non-Nissen fundoplication group ( p < 0.01 ) . CONCLUSIONS Compared with cerebral palsy-children without Nissen fundoplication , those with Nissen fundoplication have postpr and ial symptoms more frequently after receiving a rapid emptying meal . Gastric emptying alone , however , does not seem to explain the symptom occurrence . Clinical Trials.gov : UUSKBK 28200706 |
12,490 | 28,493,210 | There was no evidence that any dressing significantly reduced surgical-site infection rates compared with any other dressing .
Conclusion The evidence available in the current literature suggests that advanced dressings such as film and Hydrofibre dressings have fewer wound complications and better fluid h and ling capacity .
However , insufficient evidence is available to determine whether the use of these advanced dressings reduce periprosthetic joint infection | Background Various types of dressing material s are available for wound care following hip and knee arthroplasty .
However , it is unclear if one material is more beneficial than the others in terms of wound complications and fluid h and ling capacity .
Research questions We performed a meta- analysis of r and omized controlled trials comparing alternative wound dressing material s for the post-operative management of wounds following THA and TKA with respect to ( 1 ) incidence of wound complications including infection and ( 2 ) fluid h and ling capacity . | Purpose We prospect ively compared two types of dressing ( conventional gauze-based versus absorbing hydrofibre ) after primary total hip ( THA ) or knee ( TKA ) arthroplasties . Methods Eighty c and i date s for THA ( n = 40 ) or TKA ( s = 40 ) were r and omized : gauze-based versus hydrofibre absorbing ( Aquacel ® , ConvaTec ) . The two groups were comparable at baseline . Results There was a statistically significant decrease of dressing changes in the hydrofibre group ( p = 0.0006 ) . Two patients from the conventional group presented minor wound complications . Nurses ’ satisfaction was significantly higher in the hydrofibre group considering the adherence ( p = 0.04 ) and flexibility ( p = 0.03 ) . Patients experienced a higher satisfaction with respect to ease of movement ( p = 0.01 ) in the hydrofibre group . The cosmetic appearance of the scars six weeks after surgery was found to be similar between groups . Conclusions Our findings support an overall improved comfort for the patients and the medical staff by using hydrofibre dressings after primary THA and TKA . The reduction of required dressing changes was observed also OBJECTIVE To compare the performance of Hydrofiber and alginate dressings used in the treatment of primary hip arthroplasty wounds . METHOD Patients were r and omised into one of two groups , receiving either a Hydrofiber or an alginate dressing . Outcome measures , assessed by daily observations , included skin damage ( erythema , blisters and skin injuries ) and the dressing 's ability to h and le exu date s. Photos of the dressing and the skin area around wounds were taken . Patients noted skin problems , discomfort at mobilisation and pain at dressing removal . RESULTS In the alginate group , there were fewer blisters in the wound area compared with the Hydrofiber group ( 7 % versus 18 % , p=0.03 ) . During dressing removal , fewer patients in the alginate group reported pain than patients in the Hydrofiber group ( 2.1 % versus 15 % , p=0.01 ) CONCLUSION We recommend the use of both dressings following total hip arthroplasty , although the alginate would be our first choice , as we found fewer blisters when using alginate dressings as opposed to Hydrofiber dressings . CONFLICT OF INTEREST None Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Postoperative wound infection is a preventable risk . One potential postoperative complication is blistering , which leads to increased pain , delayed healing , and higher care costs . The incidence of wound blisters has been reported to be between 6 and 24 % . The aim of this study is to assess whether the risks of postoperative blistering and wound infections within the first 6 days postsurgery will be reduced using a special dressing compared to a st and ard one . Methods / Design This is a r and omized clinical trial in a University hospital . Patients presenting for knee or hip arthroplasty or spine procedures will be assessed against study inclusion and exclusion criteria . After giving written informed consent , patients will be r and omized to participate in the 7-day study during hospitalization . One hundred patients will be r and omized per group . The primary outcome measure is blistering incidence from day 0 to day 6 postsurgery . Photo documentation will be evaluated in a blinded manner by the Clinical Evaluation Committee ( CEC ) . Discussion A new dressing will be compared to the st and ard wound dressing regarding the risk of postoperative blistering , wound infection , and patient comfort . This study will assess the potential advantages of a modern wound dressing . Trial registration Clinical Trials.gov identifier NCT01988818 ( Entered 13 November 2011 ) OBJECTIVE To investigate the effect of three postoperative dressings on orthopaedic wound healing . METHOD Three hundred orthopaedic patients were divided into three treatment groups and allocated to management with one of three dressings : Primapore , Tegaderm with pad , and OpSite Post-Op . Staff completed a question naire to evaluate the wound progression . Outcome measures were the presence of infection , blistering and the number of dressing changes required . RESULTS There was a significantly lower incidence of blistering with OpSite Post-Op ( 6 % ) than Tegaderm with pad ( 16 % ) and Primapore ( 24 % ) ( p<0.001 ) . Patients in the OpSite Post-Op group had the lowest exu date levels . CONCLUSION Dressings that employ a clear film and have a high moisture vapour transmission rate have been shown to reduce both the rate of blistering and wound discharge . The additional expense inherent in using such dressings may , in reality , prove cost-effective because of the reduced need for dressings changes and the subsequent earlier discharge of these patients from hospital with an uncomplicated wound BACKGROUND Tape blisters after hip surgery can be a source of postoperative morbidity and can increase patient discomfort . The purpose of this prospect i ve study was to compare two different types of tape to determine whether the type of tape influences the rate of blister formation . METHODS Ninety-nine patients ( 100 hips ) were enrolled in the study . Patients were r and omized into one of two treatment groups : one treated with a nonstretchable silk tape and one treated with a perforated , stretchable cloth tape . After surgery , the assigned tape was applied over the postoperative dressing with care not to produce skin tension . At the first dressing change , the presence or absence of blisters was recorded as were the number , size , location , and type of any blisters . The presence or absence of tape blisters was recorded at the time of each subsequent dressing change . RESULTS A tape blister developed on twenty-five hips in twenty-five patients . The risk of a blister developing was 41 % ( twenty of forty-nine patients ) when the nonstretchable silk tape was used and 10 % ( five of fifty patients ) when the perforated cloth tape was used ( relative risk = 4.08 , 95 % confidence interval = 1.53 to 10.87 , p = 0.005 ) . We found no association between formation of tape blisters and the age or gender of the patient , number of medical comorbidities , smoking history , results of nutritional assessment , or type of surgery . CONCLUSIONS The prevalence of tape blisters was significantly lower when perforated cloth tape was used than it was when nonstretchable silk tape was used Introduction : Wound blisters are formed in the epidermis adjacent to surgicalincisions and are a significant cause of morbidity following hipsurgery . This study was design ed to compare two commonly used primary dressings , namely a nonadherent absorbable ( NAA ) dressing and paraffintulle gras ( PTG ) . Monitoring for the subsequent development of woundblisters in the epidermis adjacent to the surgical incision wasthen undertaken It was recently reported that use of a perforated , stretchable cloth tape instead of silk tape reduced the incidenc of postoperative blisters around the hip from 41 % to 10 % . The present prospect i ve r and omized study was conducted to determine whether use of spica b and age ( vs the cloth tape ) could further reduce or eliminate the incidence of these blisters . Patients were r and omized to 2 treatmen groups : perforated , stretchable cloth tape ( Hypafix ; Smit & Nephew , Memphis , Tenn ) and elastic spica b and age tha was started at the lower thigh and was extended aroun the hip and abdomen . After surgery , cloth tape or spic b and age was applied over the postoperative dressing , with care taken not to produce skin tension . At the first dressing change , presence or absence of blisters was recorded , along with their number , size , location , and type . All subsequent dressing changes were done much as they wer at surgery , using the assigned type of dressing . Presence or absence of blisters was recorded at each subsequent dressing change . Two hundred ninety-four patients ( 300 hips ) were enrolled . Twenty-two ( 7.33 % ) of the 300 hips developed a blister . Risk for developing a blister was 10 % with the cloth tape versus 4.67 % with the elastic spica b and age ( P < .09 ) . Surgery type ( arthroplasty vs open reduction and internal fixation [ ORIF ] , P < .03 ) and surgery duration ( P < .05 ) had more of an effect on postoperative blister formation than dressing type Wound care following lower limb arthroplasty has not been subject to in-depth clinical research , primarily because such wounds usually heal without complication . However , when prosthetic implants are used , serious wound problems can be disastrous ( Whitehouse et al. Infect Control Hosp Epidemiol 2002;23:183 - 9 ; Lindwell OM . Clin Orthop Relat Res 1986;211:91 - 103 ) . We report the results of a prospect i ve , r and omised , controlled trial comparing a hydrofibre ( Aquacel ) and central pad ( Mepore ) dressing in the management of acute wounds following primary total hip or knee arthroplasty left to heal by primary intention . Dressing performance was measured in 61 patients receiving total hip or knee replacements . There was a significant reduction in the requirement for dressing changes before five postoperative days in the hydrofibre group ( 43 % compared with 77 % in the central pad group ) , and there were fewer blisters amongst patients in the hydrofibre group ( 13 % compared with 26 % in the central pad group ) . We conclude that there is a potential role for hydrofibre dressing in the management of arthroplasty wounds PURPOSE Postoperative wound complications , especially surgical site infections , influence the outcome after total knee arthroplasty . The purpose of our study was to compare four different wound dressings . Following research questions were asked : ( 1 ) Which dressing is associated with least wound complications ? ( 2 ) Which dressing application is the cheapest ? ( 3 ) Which dressing is most comfortable for the patient ? METHODS 111 patients undergoing a total knee arthroplasty were r and omized in 4 groups . Each group received a different dressing with its specific wound management protocol : ( 1 ) Zetuvit ® with Cosmopor E ® , ( 2 ) Zetuvit ® with Opsite Post-Op Visible ® , ( 3 ) Aquacel Surgical ® and ( 4 ) Mepilex Border ® . Follow-up evaluations were performed on the fifth postoperative day and included assessment of the wound , status of the wound dressing and the patient 's own judgment . Cumulative costs were calculated . RESULTS Clinical ly Mepilex Border ® , a silicone dressing , scored the best . No wound complications were seen in this group . The mean number of dressing renewals was 1.9 for the st and ard dressing which was significantly higher ( p<.0001 ) compared to the other dressings . Opsite Post-op Visible ® was the cheapest dressing . Mepilex Border ® had the best scores for pain , freedom of movement and general comfort . CONCLUSIONS Mepilex Border ® is the most skin-friendly dressing . The number of dressing renewals is a defining factor to calculate the costs . Mepilex Border ® appeared to be the best dressing to use after a total knee arthroplasty INTRODUCTION Cutiplast ( absorbent perforated dressing with adhesive border ; Smith & Nephew ) is commonly used following orthopaedic operation , but complications of its use have been reported . A prospect i ve , r and omised , controlled study was performed to compare the efficacy of Cutiplast versus an Aquacel ( hydrofibre dressing ; ConvaTec ) covered with Tegaderm ( vapour-permeable dressing ; 3 M ) . PATIENTS AND METHODS Two-hundred patients were r and omised to receive one of the two dressings following elective and non-elective surgery of the hip and the knee . We were able to study 183 patients . The condition of the wound and any complications such as skin blistering or signs of infection was noted as was the frequency of dressing changes . RESULTS The Aquacel and Tegaderm dressing was 5.8 times more likely to result in a wound with no complications as compared to a Cutiplast dressing ( odds ratio , 5.8 ; 95 % CI 2.8 - 12.5 ; P < 0.00001 ) . CONCLUSION Aquacel covered by Tegaderm is a superior dressing to Cutiplast following surgery to the hip and knee We conducted a r and omized controlled trial to compare efficacy of an occlusive antimicrobial barrier dressing and a st and ard surgical dressing in patients who underwent primary total joint arthroplasty . Two hundred sixty-two patients were r and omized to receive either an occlusive dressing or a st and ard dressing . Wounds were closed in identical fashion . Outcomes included wound complications , dressing changes , and patient satisfaction . With use of occlusive dressing ( vs st and ard dressing ) , wound complications ( including skin blistering ) were significantly ( P = 0.15 ) reduced ; there were significantly ( P < .0001 ) fewer dressing changes ; and patient satisfaction was significantly ( P < .0001 ) higher . Use of occlusive dressings can reduce wound complications and promote wound healing after total joint arthroplasty AIM OF THE STUDY It is important to reduce potential wound complications in total hip and total knee arthroplasty procedures . The purpose of this study was to compare the jubilee dressing method to a st and ard adhesive dressing . METHOD 124 patients ( 62 total hip replacements and 62 total knee replacements ) were r and omly selected to have either a st and ard adhesive dressing or jubilee method dressing . The number of dressing changes , incidence of blistering , leakage , appearance of inflammation , infection rate and the average stay in hospital was recorded for each patient . RESULTS The jubilee dressing significantly reduced the rate of blistering , leakage and number of dressing changes when compare to a traditional adhesive dressing ( p < 0.05 ) . The rate of inflammation and average length of stay in hospital was not significantly different between the two groups . CONCLUSION The authors recommend the use of this dressing for total hip and total knee arthroplasty procedures due to the associated lower complication rate Practitioners on an orthopaedic ward used three different types of dressing on two groups of 100 patients who had undergone hip or knee operations , and compared the number of blisters that result ed . They describe their findings OBJECTIVE To assess current wound care practice , implement a potentially improved regimen and re-evaluate practice . METHOD Two prospect i ve clinical audits were performed over a 6-month period , involving 100 patients undergoing hip or knee arthroplasty . Fifty consecutive patients with traditional dressings ( Mepore ; Mölnlycke ) were evaluated prior to a change in practice to a modern dressing ( Aquacel Surgical ; ConvaTec ) . Fifty consecutive patients were then evaluated with the new dressing to complete the audit cycle . Clinical outcome measures were wear time , number of changes , blister rate and length of hospital stay . Statistical comparisons were performed using Mann Whitney or Fisher 's exact test ( statistical significance p < 0.05 ) . RESULTS Wear time for the traditional dressing ( 2 days ) was significantly shorter than for the modern dressing ( 7 days ; p < 0.001 ) , and required more changes ( 0 vs 3 ; p < 0.001 ) . Twenty per cent of patients developed blisters with the traditional dressing compared with 4 % with the modern dressing ( p=0.028 ) . Median length of stay was the same for the modern dressing ( 4 days ) compared with the traditional dressing ( 4 days ) . In the modern dressing group , 75 % of patients were discharged by day 4 , whereas in the traditional group this took until day 6 . CONCLUSION This audit highlights the problems associated with traditional dressings with frequent early dressing changes , blistering and delayed discharge . These adverse outcomes can be minimised with a modern dressing specifically design ed for the dem and s of lower limb arthroplasty . Units planning to implement enhanced recovery regimens should consider adopting this dressing to avoid compromising patient discharge . DECLARATION OF INTEREST There were no external sources of funding for this audit ; however , one author ( JC ) received reimbursement of expenses to attend and present work at educational conferences from ConvaTec |
12,491 | 18,362,248 | In patients with essential hypertension , therapy with a weight loss diet or orlistat result ed in reductions in body weight and BP .
Although sibutramine treatment reduced body weight , it did not lower BP | Weight loss is recommended in all major guidelines for antihypertensive therapy . | OBJECTIVE To assess the effects of weight reduction with 10 mg of sibutramine or placebo on blood pressure during 24 hours ( ambulatory blood pressure monitoring ) , on left ventricular mass , and on antihypertensive therapy in 86 obese and hypertensive patients for 6 months . METHODS The patients underwent echocardiography , ambulatory blood pressure monitoring , and measurement of the levels of hepatic enzymes prior to and after treatment with sibutramine or placebo . RESULTS The group using sibutramine had a greater weight loss than that using placebo ( 6.7 % versus 2.5 % ; p<0.001 ) , an increase in heart rate ( 78.3 + /- 7.3 to 82 + /- 7.9 bpm ; p=0.02 ) , and a reduction in the left ventricular mass/height index ( 105 + /- 29.3 versus 96.6 + /- 28.58 g/m ; p=0.002 ) . Both groups showed similar increases in the levels of alkaline phosphatase and comparable adjustments in antihypertensive therapy ; blood pressure , however , did not change . CONCLUSION The use of sibutramine caused weight loss and a reduction in left ventricular mass in obese and hypertensive patients with no interference with blood pressure or with antihypertensive therapy The Trial of Antihypertensive Interventions and Management was a multicenter r and omized , placebo-controlled trial design ed to assess the effectiveness of various combinations of pharmacologic and dietary interventions in the treatment of mild hypertension ( diastolic blood pressure 90 - 100 mmHg ) . The primary outcome was blood pressure change between baseline and 6 months . The study consisted of a 3 X 3 factorial design wherein participants were r and omly allocated to nine drug-diet treatment groups . Drugs included placebo , diuretic , and beta-blocker . Diets were usual , weight loss , and low sodium/high potassium . The basic strategy was to address clinical questions of interest by comparing mean blood pressure changes of selected drug-diet combinations . This paper describes the study including experimental design , sample size considerations , statistical analysis , organizational structure , and baseline findings BACKGROUND Although it is known that plasma leptin concentrations correlate with the amount of adipose tissue in the body , little information is available on the long-term effects on leptin concentrations of changes in diet and exercise . OBJECTIVE We wanted to examine whether changes in dietary energy sources and exercise-mediated energy expenditure , alone or in combination , affect plasma leptin concentrations . DESIGN In a r and omized , 2 x 2 factorial trial , 186 men with metabolic syndrome were divided into 4 groups : diet , exercise , a combination of diet and exercise , and control . Data on dietary intake , physical fitness , and demographics were collected and plasma leptin concentrations were measured before and after a 1-y intervention period . RESULTS Plasma leptin concentrations , body mass index , and fat mass decreased in association with long-term reductions in food intake as well as increased physical activity . By adjusting for either body mass index or fat mass , we observed a highly significant reduction in plasma leptin concentration after both the diet and the exercise interventions . There was no interaction between the interventions , suggesting a direct and additive effect of changes in diet and physical activity on plasma leptin concentrations . CONCLUSION Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass Aim : The aim of our study was to comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese hypertensive patients , with a specific attention to cardiovascular effects and to side effects because of this treatment BACKGROUND In animal models , cannabinoid-1 receptor ( CB1 ) blockade produces a lean phenotype , with resistance to diet-induced obesity and associated dyslipidaemia . We assessed the effect of rimonabant , a selective CB1 blocker , on bodyweight and cardiovascular risk factors in overweight or obese patients . METHODS patients with body-mass index 30 kg/m2 or greater , or body-mass index greater than 27 kg/m2 with treated or untreated dyslipidaemia , hypertension , or both , were r and omised to receive double-blind treatment with placebo , 5 mg rimonabant , or 20 mg rimonabant once daily in addition to a mild hypocaloric diet ( 600 kcal/day deficit ) . The primary efficacy endpoint was weight change from baseline after 1 year of treatment in the intention-to-treat population . FINDINGS Weight loss at 1 year was significantly greater in patients treated with rimonabant 5 mg ( mean -3.4 kg [ SD 5.7 ] ; p=0.002 vs placebo ) and 20 mg ( -6.6 kg [ 7.2 ] ; p<0.001 vs placebo ) compared with placebo ( -1.8 kg [ 6.4 ] ) . Significantly more patients treated with rimonabant 20 mg than placebo achieved weight loss of 5 % or greater ( p<0.001 ) and 10 % or greater ( p<0.001 ) . Rimonabant 20 mg produced significantly greater improvements than placebo in waist circumference , HDL-cholesterol , triglycerides , and insulin resistance , and prevalence of the metabolic syndrome . The effects of rimonabant 5 mg were of less clinical significance . Rimonabant was generally well tolerated with mild and transient side effects . INTERPRETATION CB1 blockade with rimonabant 20 mg , combined with a hypocaloric diet over 1 year , promoted significant decrease of bodyweight and waist circumference , and improvement in cardiovascular risk factors A group of previously untreated obese hypertensive patients were started on a weight reduction programme supervised by two dietitians working in a general practice surgery . It was stressed from the beginning of the programme that reducing blood pressure was the purpose of the diet . The results of follow-up after six months are presented together with results for a control group of obese hypertensive patients not receiving dietary advice or drug therapy , but being followed by the general practitioner . The weight , systolic blood pressure and diastolic blood pressure of the dieting hypertensive group were significantly lower than those of the non-dieting group after six months . However , the drop-out rate was significantly higher for the dieting group than for the non-dieting group . The results of a separate comparison between a control group of obese normotensive patients following the same dietary programme and the group of dieting obese hypertensive patients are also presented . Attendance rates and weight loss achieved were significantly better for the hypertensive group than for the normotensive group after 12 months . Weight reduction appears to be an effective first-line therapy for approximately 50 % of obese patients with mild to moderate hypertension , and raised blood pressure appears to provide motivation for such patients to attend a dietitian 's clinic and to lose weight BACKGROUND Few trials have evaluated the effects of reduced sodium intake in older individuals , and no trial has examined the effects in relevant subgroups such as African Americans . PATIENTS AND METHODS The effects of sodium reduction on blood pressure ( BP ) and hypertension control were evaluated in 681 patients with hypertension , aged 60 to 80 years , r and omly assigned to a reduced sodium intervention or control group . Participants ( 47 % women , 23 % African Americans ) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication . Three months after the start of intervention , medication was withdrawn . The primary end point was occurrence of an average systolic BP of 150 mm Hg or more , an average diastolic BP of 90 mm Hg or more , the resumption of medication , or a cardiovascular event during follow-up ( mean , 27.8 months ) . RESULTS Compared with control , mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group ( P<.001 ) ; significant reductions in sodium excretion occurred in subgroups defined by sex , race , age , and obesity . Prior to medication withdrawal , mean reductions in systolic and diastolic BPs from the reduced sodium intervention , net of control , were 4.3 mm Hg ( P<.001 ) and 2.0 mm Hg ( P = .001 ) . During follow-up , an end point occurred in 59 % of reduced sodium and 73 % of control group participants ( relative hazard ratio = 0.68 , P<.001 ) . In African Americans , the corresponding relative hazard ratio was 0.56 ( P = .005 ) ; results were similar in other subgroups . In dose-response analyses , end points were progressively less frequent with greater sodium reduction ( P for trend = .002 ) . CONCLUSION A reduced sodium intake is a broadly effective , nonpharmacologic therapy that can lower BP and control hypertension in older individuals This 6-month r and omized study evaluated the safety and efficacy of sibutramine in 57 overweight Hispanic patients with hypertension . Following a 2-week washout to confirm the diagnosis of hypertension , antihypertensive medication was adjusted to achieve a blood pressure less than 140/90 mm Hg before institution of either sibutramine 10 mg or placebo once a day . A body mass index in excess of 27 kg/m2 was required for entry . At study end , weight had changed from 75.4±9.6 to 70.0±9.5 kg in the sibutramine group and from 77.9±9.0 to 74.5±9.4 kg in the placebo group . In the sibutramine group , systolic blood pressure was 127.8±5.8 mm Hg after stabilization and 125.2±8.5 mm Hg after completion of the trial ; respective values for diastolic blood pressure were 82.4±3.7 and 81.5±4.6 mm Hg . With placebo , blood pressure dropped from 129.0±7.1/80.9±4.9 mm Hg to 122.8±9.7/80.3±5.4 mm Hg at the same timepoints . In the sibutramine group , 14 patients reported 21 adverse events , most frequently headache ( n=5 ) , constipation ( n=4 ) , and dry mouth ( n=4 ) . In the placebo group , 13 patients had 20 adverse events . Sibutramine is safe and effective in overweight Hispanic patients with hypertension , but monitoring of blood pressure and titration of antihypertensive medication are necessary OBJECTIVE Plasma renin activity was measured at baseline and 6 months in a trial of nonpharmacologic therapy of mild hypertension to determine whether plasma renin activity predicts the diastolic blood pressure ( DBP ) response to nonpharmacologic therapy . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of volunteers from the general community with mild hypertension ( DBP between 90 and 100 mm Hg ) , off all antihypertensive therapy at baseline , treated in special research clinics ( n = 593 ) . INTERVENTIONS Subjects were r and omly assigned to usual , weight loss , or low sodium/high potassium diet and then r and omly assigned to receive placebo , chlorthalidone , or atenolol . MAIN OUTCOME MEASURES Renin was analyzed as plasma renin activity and as a renin index ( logarithm of 24-hour urinary sodium excretion times logarithm of plasma renin activity ) ( 593 patients at baseline and 6 months ) to correct for varied sodium intakes . The DBP was measured using the r and om zero device . RESULTS Change in DBP at 6 months could be predicted from baseline plasma renin activity or renin index . The DBP was decreased after 6 months of therapy by 2 mm Hg for each unit increase in baseline plasma renin activity and by 0.16 mm Hg for each unit increase in baseline renin index . Patients in the highest renin index quartile had a greater DBP response to atenolol therapy , and patients in the lowest renin index quartile had a greater DBP response to chlorthalidone therapy . Weight loss diet achieved a greater reduction in DBP in patients with higher baseline renin index and had an additive effect on DBP response in both of the drug groups . Patients on a weight loss diet receiving placebo in the highest baseline renin index quartile had a reduction in DBP of 12.4 mm Hg , compared with 4.4 mm Hg in the lowest baseline renin index quartile ( P = .009 ) . A low sodium/high potassium diet had a lesser effect than a weight loss diet on pharmacologic therapy . As with the weight loss diet , patients on a low sodium/high potassium diet in the highest baseline renin index quartile had a greater reduction in DBP than patients in the lowest baseline renin index quartile . CONCLUSIONS These data suggest a significant relationship between baseline levels of plasma renin index and the likelihood of success of nonpharmacologic treatment of hypertension OBJECTIVES To examine the effect of diet and exercise-induced weight loss on bone mineral density in overweight postmenopausal women DESIGN A 1-year prospect i ve , r and omized clinical trial . SETTING Two university medical school research centers . PARTICIPANTS Sixty-seven overweight postmenopausal women , a subset of the women who participated in the Trial of Nonpharmacological Interventions in the Elderly ( TONE ) to control hypertension . The participants were assigned r and omly to one of four groups : usual care , weight loss only , sodium restriction only , or combined weight loss/sodium restriction . INTERVENTION All TONE participants in the treatment groups attended regular dietary intervention sessions to lose weight , reduce sodium intake , or both that they might refrain from using antihypertensive medications for a period of 15 to 36 months ( median = 29 months ) . MEASUREMENTS Bone mineral density ( BMD ) assessed by dual energy X-ray absorptiometry ( DXA ) , serum and urine markers of bone metabolism , and other demographic and clinical data were collected at baseline , 6 months , and 12 months . RESULTS Women assigned to the weight loss interventions lost 9.2 + /- 1.2 lbs ( mean + /- SE ) at 6 months and 7.7 + /- 2.0 lbs at 12 months compared with 1.8 + /- 1.0 lbs at 6 months and 1.9 + /- 1.6 lbs at 12 months for those assigned to no weight loss intervention ( P < .0001 ) . Weight loss was correlated with a decrease in total body BMD ( P = .004 ) and an increase in osteocalcin ( P = .004 ) after controlling for baseline bone measures , intervention assignment , and other baseline covariates . Regression analyses indicated that total body BMD decreased by 6.25 + /- 2.06 g/cm2 x 10 - 4 for each pound of weight loss . CONCLUSIONS Voluntary weight loss in overweight postmenopausal women is associated with modest decrease in total body BMD . Clinicians recommending weight loss for older postmenopausal women may need to include recommendations for reducing the risk of bone loss BACKGROUND Weight loss and sodium reduction programs are effective in treating hypertension , but there is little information about the persistence of the benefit after discontinuation of the intervention . METHODS The Trial of Nonpharmacologic Interventions in the Elderly ( TONE ) was a four-center controlled clinical trial of weight loss , reduced sodium intake , or both in maintaining normotension after withdrawal of antihypertensive drug therapy in older men and women whose hypertension was controlled with a single antihypertensive medication . Information on maintenance of normotension without need for drug therapy was obtained on 222 of 223 participants at the Robert Wood Johnson Medical School clinical center on average of 48.4 months ( range 45 to 54 months ) after the end of TONE . RESULTS At the end of TONE follow-up , 43 % of participants in the combined intervention group were off medication compared with 25 % in the usual care group ( P = .011 ) . At 48 months after the end of TONE and discontinuation of contact of the participants with the clinical center , 23 % of the combined intervention group v 7 % in the usual care group were off medication ( P = .012 ) . CONCLUSIONS Some benefits of structured dietary intervention appears to persist long term in a significant number of patients after discontinuation of the intervention The Trial of Antihypertensive Interventions and Management ( T AIM ) was a multicenter r and omized drug ( double-blind , placebo-controlled)-diet trial . One objective of T AIM was to assess the long-term ability of a low-sodium/high-potassium ( Na+ decreases/K+ increases ) diet to maintain blood pressure control in persons at 110 % to 160 % ideal weight with diastolic blood pressure from 90 to 100 mm Hg who were on no drugs or on low-dose monotherapy . Participants , 56 % men and 33 % black , were r and omized to usual diet ( n = 296 ) or to Na+ decreases/K+ increases diet ( n = 291 ) and within each diet group to placebo , 25 mg/day chlorthalidone , or 50 mg/day atenolol . Treatment failure was defined as lack of blood pressure control requiring additional drugs according to specified criteria . At baseline , the mean value for age was 48 years ; blood pressure , 143/93 mm Hg ; weight , 88 kg ; and 24-h urinary sodium and potassium excretion rates , 133 and 57 mmol/day , respectively . At 3 years , the net difference in 24-h urinary sodium/potassium excretion rates between the Na+ decreases/K+ increases and the usual diet groups was -30 and + 11 mmol/L/day . The relative risk of treatment failure for Na+ decreases/K+ increases compared to usual diet by proportional hazards regression was 0.95 ( P = .71 ) . This study provides no support for the sole use of a low-sodium/high-potassium diet as a practical therapeutic strategy in maintaining blood pressure control in the moderately obese OBJECTIVE It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity . A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated . We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight , and thus the incidence of type 2 diabetes , in obese patients . RESEARCH DESIGN AND METHODS In a 4-year , double-blind , prospect i ve study , we r and omized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo , three times daily . Participants had a BMI > /=30 kg/m2 and normal ( 79 % ) or impaired ( 21 % ) glucose tolerance ( IGT ) . Primary endpoints were time to onset of type 2 diabetes and change in body weight . Analyses were by intention to treat . RESULTS Of orlistat-treated patients , 52 % completed treatment compared with 34 % of placebo recipients ( P < 0.0001 ) . After 4 years ' treatment , the cumulative incidence of diabetes was 9.0 % with placebo and 6.2 % with orlistat , corresponding to a risk reduction of 37.3 % ( P = 0.0032 ) . Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT . Mean weight loss after 4 years was significantly greater with orlistat ( 5.8 vs. 3.0 kg with placebo ; P < 0.001 ) and similar between orlistat recipients with impaired ( 5.7 kg ) or normal glucose tolerance ( NGT ) ( 5.8 kg ) at baseline . A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group ( 3.6 vs. 1.4 kg ; P < 0.001 ) . CONCLUSIONS Compared with lifestyle changes alone , orlistat plus lifestyle changes result ed in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinical ly representative obese population . Difference in diabetes incidence was detectable only in the IGT subgroup ; weight loss was similar in subjects with IGT or NGT [ correction ] The Trial of Antihypertensives Interventions and Management ( T AIM ) was a multicenter double-blind placebo-controlled clinical trial of drug and diet combinations for the treatment of mild hypertension among 878 participants , ages 21 to 65 , 110 % to 160 % ideal weight , and with baseline diastolic blood pressure 90 to 100 mm Hg . The drugs used were placebo , chlorthalidone ( 25 mg/daily ) or atenolol ( 50 mg/daily ) . The diets studied were usual , weight loss , sodium reduction/potassium increase . Trial end points were 6-month diastolic blood pressure change , cardiovascular risk change , and quality of life change . Either drug combined with weight loss produced the greatest blood pressure reduction of 15 mm Hg , compared to 8 mm Hg on placebo/usual diet . Adding sodium restriction to either drug did not enhance blood pressure lowering effect . Drugs outperformed diet in terms of antihypertensive effect . However , those on placebo and assigned to weight reduction who lost more than 4.5 kg and those on sodium restriction who reduced sodium to less than 70 mEq daily lowered blood pressure to a similar extent as those on either of the two drugs alone . Cardiovascular risk at 6 months relative to baseline ranged from 0.85 in weight loss/atenolol subgroup to 1.04 in the usual diet/chlorthalidone subgroup . Blacks were more responsive to chlorthalidone plus weight loss and whites to atenolol plus weight loss . Quality of life , as measured by scales of distress and well-being , was favorably affected by weight reduction . Although there were few side effects of the drugs and most patients improved on most parameters , sexual complaints were worsened among those on chlorthalidone and usual diet compared to placebo . ( ABSTRACT TRUNCATED AT 250 WORDS CONTEXT Orlistat , a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30 % , may promote weight loss and reduce cardiovascular risk factors . OBJECTIVE To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years . DESIGN R and omized , double-blind , placebo-controlled study conducted from October 1992 to October 1995 . SETTING AND PARTICIPANTS Obese adults ( body mass index [ weight in kilograms divided by the square of height in meters ] , 30 - 43 kg/m2 ) evaluated at 18 US research centers . INTERVENTION Subjects received placebo plus a controlled-energy diet during a 4-week lead-in . On study day 1 , the diet was continued and subjects were r and omized to receive placebo 3 times a day or orlistat , 120 mg 3 times a day , for 52 weeks . After 52 weeks , subjects began a weight-maintenance diet , and the placebo group ( n = 133 ) continued to receive placebo and orlistat-treated subjects were rer and omized to receive placebo 3 times a day ( n = 138 ) , orlistat , 60 mg ( n = 152 ) or 120 mg ( n = 153 ) 3 times a day , for an additional 52 weeks . MAIN OUTCOME MEASURES Body weight change and changes in blood pressure and serum lipid , glucose , and insulin levels . RESULTS A total of 1187 subjects entered the protocol , and 892 were r and omly assigned on day 1 to double-blind treatment . For intent-to-treat analysis , 223 placebo-treated subjects and 657 orlistat-treated subjects were evaluated . During the first year orlistat-treated subjects lost more weight ( mean + /- SEM , 8.76+/-0.37 kg ) than placebo-treated subjects ( 5.81+/-0.67 kg ) ( P<.001 ) . Subjects treated with orlistat , 120 mg 3 times a day , during year 1 and year 2 regained less weight during year 2 ( 3.2+/-0.45 kg ; 35.2 % regain ) than those who received orlistat , 60 mg ( 4.26+/-0.57 kg ; 51.3 % regain ) , or placebo ( 5.63+/-0.42 kg ; 63.4 % regain ) in year 2 ( P<.001 ) . Treatment with orlistat , 120 mg 3 times a day , was associated with improvements in fasting low-density lipoprotein cholesterol and insulin levels . CONCLUSIONS Two-year treatment with orlistat plus diet significantly promotes weight loss , lessens weight regain , and improves some obesity-related disease risk factors OBJECTIVE To evaluate treatment of mild hypertension using combinations of diet and low-dose pharmacologic therapies . DESIGN Multicenter , r and omized , placebo-controlled clinical trial . SETTING Three university-based tertiary care centers . PATIENTS Patients ( 697 ) 21 to 65 years of age with diastolic blood pressure between 90 and 100 mm Hg as well as weight between 110 % and 160 % of ideal weight . INTERVENTION Patients were stratified by clinical center and race and were r and omly assigned to one of three diets ( usual , low-sodium and high-potassium , weight loss ) and one of three agents ( placebo , chlorthalidone , and atenolol ) . MEASUREMENTS Changes in measures of sexual problems , distress , and well-being after 6 months of therapy were analyzed . MAIN RESULTS Low-dose chlorthalidone and atenolol produced few side effects , except in men . Erection-related problems worsened in 28 % ( 95 % CI , 15 % to 41 % ) of men receiving chlorthalidone and usual diet compared with 3 % ( CI , 0 % to 9 % ) of those receiving placebo and usual diet ( P = 0.009 ) and 11 % ( CI , 2 % to 20 % ) of those receiving atenolol and usual diet ( P greater than 0.05 ) . The weight loss diet ameliorated this effect . The low-sodium diet with placebo was associated with greater fatigue ( 34 % ; CI , 23 % to 45 % ) than was either usual diet ( 18 % ; CI , 10 % to 27 % ; P = 0.04 ) or weight reduction ( 15 % ; CI , 7 % to 23 % ; P = 0.009 ) . The low-sodium diet with chlorthalidone increased problems with sleep ( 32 % ; CI , 22 % to 42 % ) compared with chlorthalidone and usual diet ( 16 % ; CI , 8 % to 24 % ; P = 0.04 ) . The weight loss diet benefited quality of life most , reducing total physical complaints ( P less than 0.001 ) and increasing satisfaction with health ( P less than 0.001 ) . Total physical complaints decreased in 57 % to 76 % of patients depending on drug and diet group , and were markedly decreased by weight loss . CONCLUSION In general , low-dose antihypertensive drug therapy ( with chlorthalidone or atenolol ) improves rather than impairs the quality of life ; however , chlorthalidone with usual diet increases sexual problems in men OBJECTIVE To compare the effectiveness of different approaches to participant enrollment in a behavior modification trial . DESIGN Concurrent , prospect i ve evaluation performed in context of recruitment for a r and omized , controlled trial . SETTING Four study centers located in Baltimore , Maryl and , Memphis , Tennessee New Brunswick , New Jersey , and Winston-Salem , North Carolina . PARTICIPANTS Men and women aged 60 to 80 years who were being treated with a prescription medication for control of hypertension . MAIN OUTCOME MEASURES Visit counts and percent yields were assessed at each stage of the screening and r and omization process . Logistic regression was used to contrast the r and omization yields for different recruitment strategies and to explore the impact of sociodemographic characteristics and geographic location on recruitment yields . RESULTS The overall r and omization yields from a prescreen contact and a first screening visit to enrollment in the trial were 11 % and 31 % , respectively . R and omization yields varied significantly by participant age , education , and marital status . CONCLUSIONS Our results demonstrate the feasibility of recruitment for trials of nonpharmacologic interventions in older people and suggest that mass mailing and mass media advertising campaigns provide an effective means of enrolling in such studies participants with a broad range of personal characteristics In most clinical trials it is problematic to recruit enough patients within a reasonable time period . Prolonged or inefficient recruitment or both can have negative scientific and economic consequences . The XENDOS ( XENical in the prevention of Diabetes in Obese Subjects ) study is an ongoing r and omized , double-blind , placebo-controlled , prospect i ve , multicenter trial investigating whether orlistat combined with hypocaloric diet and moderate physical exercise can reduce the incidence of diabetes in obese subjects . To implement the XENDOS protocol and recruit the study patients , we design ed a system for central ized patient recruitment and central ized scheduling of patients and staff at the 22 collaborating centers . The recruitment and inclusion phase was divided into a series of different consecutive examinations of increasing complexity . Relatively simple initial examinations enabling a large throughput of patients were followed by more detailed examinations of fewer subjects , by then known to fulfil some of the study -specific requirements . With the aid of object-oriented techniques , the software was modularized to enable concurrent engineering . We also selected a structure where plug-in modules h and ling specific tasks could be added to the system as needed . The design was supported by a flow-oriented view of the progress of the patients through the study . With this overall solution we managed to include 3305 subjects ( 98.8 % of the requested number ) within less than 4 months . The sex distribution ( 44.8 % men ) and the number of patients with impaired glucose tolerance ( IGT ) , ( 21.1 % ) were in close accordance with , or far better than , the requirements of the protocol ( 45 % men , at least 10 % IGT patients ) . The basic design of the XENDOS information system can be adapted to fulfil the requirements of other study protocol s within the fields of obesity , diabetes , hypertension , coronary heart disease , etc . Shortening the recruitment and inclusion phase of large clinical trials is of great value both to be medical society and the pharmaceutical industry Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo , although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure ( BP ) . This 52-week , placebo-controlled , double-blind , r and omised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese ( body mass index ( BMI ) 27–40 kg/m2 ) , hypertensive patients . At r and omisation , hypertension was well controlled ( ⩽95 mm Hg diastolic blood pressure ( DBP ) ) with an angiotensin-converting enzyme ( ACE ) inhibitor , with or without concomitant thiazide diuretic therapy . Therapy for hypertension continued for the 52 weeks of the study . Sibutramine 20 mg produced significantly greater weight loss compared with placebo : 4.5 kg with sibutramine compared with 0.4 kg with placebo ( last observation carried forward ( LOCF ) ; P ⩽ 0.05 ) . A total of 62 patients ( 42.8 % ) treated with sibutramine lost ⩾5 % of their body weight compared with six patients ( 8.3 % ) treated with placebo ; 19 patients ( 13.1 % ) treated with sibutramine lost ⩾10 % of their body weight compared with two patients ( 2.8 % ) treated with placebo ( LOCF ; P⩽ 0.05 for both comparisons ) . Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment . After 52 weeks , the differences between placebo treatment and sibutramine treatment for both mean supine systolic blood pressure ( SBP ) and DBP were approximately 3 mm Hg : mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment ( LOCF ; P = 0.004 ) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine ( LOCF ; P = 0.0497 ; both comparisons , sibutramine vs placebo ) . The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points . Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute ( bpm ) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment ( P < 0.001 ) . M and ated withdrawals from the study due to protocol -defined changes in BP were not statistically different between the two treatment groups . Greater favourable changes in lipid profile , serum glucose , and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group . Sibutramine was well tolerated . This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor , with or without concomitant thiazide diuretic therapy , sibutramine safely and effectively achieves weight loss without compromising good BP control The aim of the study was to test the effect of a non-pharmacological weight reduction program on cardiovascular risk factors among overweight hypertensives in a primary health care setting . Forty-nine overweight hypertensive patients completed the 12-month program . The patients were r and omly allocated into either intervention or control groups . The examinations included interviews by a nutritionist , pertinent laboratory tests , and a medical examination . The intervention involved an individually planned energy-restricted diet of 1000 - 1500 kcal per day , weekly discussion s , and various leaflets on diet modification and on increase of physical activity . The mean body weight was reduced by 5 kg in the intervention group , but remained unchanged in the control group . The intervention group reduced their fat intake by 14 g/day while the control group increased it by 9 g/day on the average . In the intervention group , the total serum cholesterol decreased , HDL-cholesterol increased and triglycerides decreased significantly . The systolic blood pressure fell by 8 mm Hg and 15 mm Hg in the intervention and control groups , respectively . The diastolic blood pressure fell on average by 11 mm Hg in both groups . The results demonstrate the comprehensive weight reduction program to be effective in the control of cardiovascular risk factors Mental health and quality of life were assessed before and after a one-year exercise and diet intervention among 219 healthy individuals , aged 41 - 50 years , with elevated risk factors for cardiovascular disease . The participants were r and omized to four groups : diet ( n = 55 ) , diet and exercise ( n = 67 ) , exercise ( n = 54 ) and no active intervention ( n = 43 ) . Quality of life was measured with one eight-item scale and two one-item scales . Mental health was measured by the General Health Question naire ( 30-item version ) . Depression , anxiety , feelings of competence and self-esteem , coping and social dysfunction were measured using subscales of the General Health Question naire . Somatic anxiety was measured by the anxiety subscale of the Symptom Check List-90 . Exercise improved the total GHQ scores , perceived competence/self-esteem , and coping as measured by the GHQ subscales . There were no significant effects of diet or exercise on quality of life , depression or anxiety . A high rate of participation in the exercise programme ( > 70 % ) was associated with greater improvements in total GHQ scores , anxiety , perceived competence/self-esteem and coping The Fifth Report of the Joint National Committee on Detection , Evaluation , and Treatment of High Blood Pressure recommends that attempts to discontinue antihypertensive drug therapy be considered after blood pressure ( BP ) has been controlled for 1 year . However , discontinuation of drug therapy could unmask underlying conditions and precipitate clinical cardiovascular events . The Trial of Nonpharmacologic Interventions in the Elderly ( TONE ) was a clinical trial of the efficacy of weight loss and /or sodium reduction in controlling BP after withdrawal of drug therapy in patients with a BP < 145/85 mm Hg on 1 antihypertensive medication . Of 975 participants , 886 entered the drug withdrawal phase of the trial and 774 were successfully withdrawn from their medications . Thirty-three events ( stroke , transient ischemic attack , myocardial infa rct ion , arrhythmia , congestive heart failure , angina , other ) occurred between r and omization and the onset of drug withdrawal ( median time 3.6 months ) , 57 events occurred either during or after drug withdrawal ( 14.0 months ) , and 36 events occurred after resumption of antihypertensive therapy ( 15.9 months ) . Event rates per 100 person-years were 5.5 , 5.5 , and 6.8 for the 3 time periods ( p=0.84 ) in the nonoverweight group and 7.2 , 5.2 , and 5.6 ( p=0.08 ) in the overweight group . The study shows that antihypertensive medication can be safely withdrawn in older persons without clinical evidence of cardiovascular disease who do not have diastolic pressure > or = 150/90 mm Hg at withdrawal , providing that good BP control can be maintained with nonpharmacologic therapy The effect of a 1-year exercise and diet intervention program on global self-concept , perceptions of the body , physical competence , exercise mastery , social competence , social comfort , and fitness was examined with 208 healthy individuals ( 191 males , 17 females ) aged 39 - 49 years ( mean age 44.9 ) with elevated risk factors for cardiovascular disease . The relative utility of the skill development versus the self-enhancement model of the self-concept/behaviour relationship was tested . The participants were r and omized into four groups : diet ( n = 53 ) , diet and exercise ( n = 64 ) , exercise ( n = 48 ) and no active intervention ( n = 43 ) . Measurements were made by the Harter adult self perception profile ( HASPP ) and the self-perception in exercise question naire ( SPEQ ) . Two-way ANOVA analyses revealed that exercise participation , with or without diet , enhanced self-perceptions of physical mastery and ability , body perception , fitness and social comfort . The unique contribution of diet indicated enhanced body perception . No effect was found of diet or exercise on global self-concept . Exercise participation had a positive effect on perceptions of the self , and the higher the compliance with the exercise program , the stronger were the effects on the self-perceptions . This supported the skill development model of the self-concept/behaviour relationship . As the pretest self-concept scores did not predict exercise compliance , the self-enhancement model of the self-concept/behaviour relationship was not supported This study asks whether prolonged antihypertensive therapy will " cure " a substantial percent of rigorously treated hypertensive patients and whether nutritional change will add an antihypertensive effect and reduce the relapse rate . Of 584 eligible patients normotensive while receiving therapy , 496 were r and omized into control and discontinued-medication groups with and without dietary intervention . At 56 weeks , 50 % of those who were no longer receiving medication remained normotensive by study criteria . R and omization either to weight-loss group ( mean loss of 4.5 kg [ 10 lb ] ) or to sodium-restriction group ( mean reduction of 40 mEq/day ) increased the likelihood of remaining without drug therapy , with an adjusted odds ratio of 2.17 for the sodium group and 3.43 for the weight group . Highest success rates were in the nonoverweight mild hypertensives with sodium restriction ( 78 % ) and the overweight mild hypertensives who were reducing their weight ( 72 % ) . These data demonstrate that weight loss or sodium restriction , in hypertensives controlled for five years , more than doubles success in withdrawal of drug therapy OBJECTIVE To compare weight loss in blacks and whites in the Trial of Nonpharmacologic Interventions in the Elderly ( TONE ) . RESEARCH METHODS AND PROCEDURES TONE enrolled 421 overweight white and 164 overweight black adults , 60 to 79 years old , with blood pressure well-controlled on a single , antihypertensive drug . Drug therapy withdrawal was attempted 3 months after r and omization to counseling for weight loss , sodium reduction , both weight loss and sodium reduction , or to usual care , with follow-up for 15 to 36 months after enrollment . Statistical procedures included repeated measures analysis of covariance and logistic and proportional hazards regression . RESULTS In the weight-loss condition , net weight change ( in kilograms ) was -2.7 in blacks and -5.9 in whites ( p < 0.001 ; ethnic difference , p = 0.0002 ) at 6 months and -2.0 ( p < 0.05 ) in blacks and -4.9 ( p < 0.001 ) in whites at the end of follow-up ( ethnic difference , p = 0.007 ) . In weight/sodium , net weight change was -2.1 ( p < 0.01 ) in blacks and -2.8 ( p < 0.001 ) in whites at 6 months , and -1.9 in blacks and -1.7 in whites at the end of follow-up ( p < 0.05 ; ethnic difference , p > 0.5 ) . Exploratory analyses suggested a more favorable pattern of weight change in blacks than in whites from 6 months onward . There was no ethnic difference in blood pressure outcomes . DISCUSSION Whites lost more weight than blacks without , but not with , a concurrent focus on sodium reduction OBJECTIVE To evaluate the 6-month change in cardiovascular ( coronary heart disease ) risk as a function of diet and drug therapy for mild hypertension . DESIGN Collaborative r and omized , controlled clinical trial to assess the efficacy of alternative regimens in treating mild hypertension . SETTING Three university-based tertiary care centers-the Trial of Antihypertensive Interventions and Management ( T AIM ) . PATIENTS Six hundred and ninety-two men and women ages 21 to 65 years with diastolic blood pressure between 90 and 100 mm Hg and weight between 110 % and 160 % of ideal weight . MEASUREMENTS AND MAIN RESULTS Patients stratified by clinical center and race were r and omized into diet ( usual , low sodium-high potassium , weight loss ) and drug ( placebo , chlorthalidone , and atenolol ) groups result ing in nine diet plus drug combinations . The cardiovascular risk at 6-month follow-up was estimated relative to baseline in 692 participants using the Framingham Study model . Due to the blood pressure reduction , cardiovascular risk declined from baseline for all treatment groups ( except the usual diet plus chlorthalidone group because of increased cholesterol levels ) . The relative cardiovascular risk at 6 months compared to baseline ranged from 0.83 in the weight loss plus atenolol subgroup to 1.03 in the usual diet plus chlorthalidone subgroup . The active drug plus weight loss groups showed the lowest relative cardiovascular risk at 6 months . CONCLUSIONS Mild hypertension was generally reduced to desirable levels within 6 months by monotherapy . Evaluating blood pressure changes together with the risk factors indicated a differential effect on overall cardiovascular risk depending on the diet and drug used . Dietary therapy , particularly weight reduction , was important adjunctive treatment in reducing overall cardiovascular risk National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure ( BP ) . However , data to support such recommendations in older persons are virtually nonexistent . The Trials of Nonpharmacologic Intervention in the Elderly ( TONE ) is a r and omized , controlled trial that will test whether weight loss or a reduced sodium ( Na ) intake or both can maintain satisfactory BP control , without unacceptable side effects , after withdrawal of antihypertensive drug therapy . Medication-treated hypertensives ( aged 60 to 80 years ) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are r and omly assigned to one of four groups : ( 1 ) weight loss alone , ( 2 ) reduced Na intake alone , ( 3 ) combined weight loss and reduced Na intake , or ( 4 ) usual life-style ( control group ) . Overweight participants are r and omized to one of these four groups , while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group . The interventions , tailored to the needs of older persons , use behavioral approaches to accomplish intervention-specific goals ( weight loss > or = 10 lb , daily Na intake < or = 80 mEqa ) . Three months after the start of intervention , antihypertensive drug therapy is withdrawn . The primary trial end point is a BP of 150/90 mm Hg or higher , resumption of antihypertensive drug therapy , or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up . It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy BACKGROUND Obesity is a highly prevalent medical condition and is commonly accompanied by hypertension . This study assessed the efficacy and safety of treatment with sibutramine hydrochloride for promoting and maintaining weight loss in obese patients with controlled hypertension , including a subset analysis of African American patients . PATIENTS AND METHODS Obese patients with a body mass index ( BMI , calculated as weight in kilograms divided by the square of height in meters ) between 27 and 40 and a history of hypertension controlled with a calcium channel blocker ( with or without concomitant thiazide diuretic treatment ) were r and omized to receive sibutramine ( n = 150 ) or placebo ( n = 74 ) with minimal behavioral intervention for 52 weeks . African Americans constituted 36 % of enrolled patients . Efficacy assessment s were body weight and related parameters ( BMI and waist and hip circumferences ) , metabolic parameters ( serum levels of triglycerides , high-density lipoprotein cholesterol [ HDL-C ] , low-density lipoprotein cholesterol [ LDL-C ] , total cholesterol , glucose , and uric acid ) , and quality -of-life measures . Safety assessment s included recording of blood pressure , pulse rate , adverse events , and reasons for discontinuation . RESULTS For patients receiving sibutramine , weight loss occurred during the first 6 months of the trial and was maintained to the end of the 12-month treatment period . Among patients receiving sibutramine , 40.1 % lost 5 % or more of body weight ( 5 % responders ) and 13.4 % lost 10 % or more of body weight ( 10 % responders ) compared with 8.7 % and 4.3 % of patients in the placebo group , respectively ( P<.05 ) . Changes in body weight were similar among African Americans and whites . Sibutramine-induced weight loss was associated with significant improvements in serum levels of triglycerides , HDL-C , glucose , and uric acid . Waist circumference and quality -of-life measures also improved significantly in patients receiving sibutramine . Sibutramine-treated patients had small but statistically significant mean increases in diastolic blood pressure ( 2.0 mm Hg ) and pulse rate ( 4.9 beats/min ) compared with placebo-treated patients ( -1.3 mm Hg and 0.0 beats/min ; P<.05 ) ; these changes were similar among African Americans and whites . Most adverse events were mild to moderate in severity and transient . The most common adverse event result ing in discontinuation among patients receiving sibutramine was hypertension ( 5.3 % of patients receiving sibutramine vs 1.4 % of patients receiving placebo ) . CONCLUSIONS In obese patients with controlled hypertension , sibutramine was an effective and well-tolerated treatment for weight loss and maintenance . Sibutramine-induced weight loss result ed in improvements in serum levels of triglycerides , HDL-C , uric acid , and glucose , and in waist circumference and quality -of-life measures . Blood pressure and heart rate increased by a small amount . Efficacy and safety profiles for sibutramine among African American and white obese patients with controlled hypertension were similar AIM To assess the effect of orlistat on body weight and concomitant diseases in patients with body mass index ( BMI ) of > 28 kg/m2 and poorly controlled type 2 diabetes , hypertension or hypercholesterolaemia . METHODS This trial was a six-month , r and omized , double-blind , placebo-controlled study of orlistat 120 mg three times daily plus a mildly reduced-calorie diet . 1004 obese patients ( BMI 28 - 40 kg/m2 ) were included by 253 private endocrinologists and received orlistat ( n = 499 ) or placebo ( n = 505 ) . Patients were stratified by concomitant disorder ( type 2 diabetes , n = 193 ; hypertension , n = 614 ; hypercholesterolaemia , n = 197 ) . Body weight , anthropometry , lipid and glycaemic control parameters and blood pressure . RESULTS After six months , orlistat produced a significantly greater weight loss than placebo in type 2 diabetes ( -4.2 % vs. -1.4 % ) , hypertension ( -6.2 % vs. -1.9 % ) and hypercholesterolaemia ( -5.5 % vs. -2.3 % ) groups ( p < 0.0001 for all ) . There was a greater decrease in HbA(1c ) in the type 2 diabetes group ( -0.54 vs. -0.18 % ; p = 0.002 ) and low-density lipoprotein (LDL)-cholesterol in the hypercholesterolaemia group ( -11.7 % vs. -4.5 % ; p = 0.004 ) with orlistat vs. placebo . Early weight loss ( > or = 5 % at 12 weeks ) was associated with the highest weight loss in each group , and the highest decreases in HbA1c , LDL-cholesterol and diastolic blood pressure in patients with type 2 diabetes , hypercholesterolaemia and hypertension , respectively , at six months . The incidence of adverse events was similar for orlistat and placebo , except for certain generally well-tolerated gastrointestinal events that were more common with orlistat . CONCLUSION Orlistat plus a mildly reduced-calorie diet produced clinical ly meaningful weight loss and improvements in risk factors in overweight and obese patients with poorly controlled type 2 diabetes , hypertension or hypercholesterolaemia BACKGROUND Rimonabant , a selective cannabinoid type 1 receptor blocker , reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients . The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas . METHODS 1047 overweight or obese type 2 diabetes patients ( body-mass index 27 - 40 kg/m2 ) with a haemoglobin A1c ( HbA1c ) concentration of 6.5 - 10.0 % ( mean 7.3 % [ SD 0.9 ] at baseline ) already on metformin or sulphonylurea monotherapy were given a mild hypocaloric diet and advice for increased physical activity , and r and omly assigned placebo ( n=348 ) , 5 mg/day rimonabant ( 360 ) or 20 mg/day rimonabant ( 339 ) for 1 year . Two individuals in the 5 mg/day group did not receive double-blind treatment and were thus not included in the final analysis . The primary endpoint was weight change from baseline after 1 year of treatment . Analyses were done on an intention-to-treat basis . This trial is registered at Clinical Trials.gov , number NCT00029848 . FINDINGS 692 patients completed the 1 year follow-up ; numbers in each group after 1 year were much the same . Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group ( placebo : -1.4 kg [ SD 3.6 ] ; 5 mg/day : -2.3 kg [ 4.2 ] , p=0.01 vs placebo ; 20 mg/day : -5.3 kg [ 5.2 ] , p<0.0001 vs placebo ) . Rimonabant was generally well tolerated . The incidence of adverse events that led to discontinuation was slightly greater in the 20 mg/day rimonabant group , mainly due to depressed mood disorders , nausea , and dizziness . INTERPRETATION These data indicate that 20 mg/day rimonabant , in combination with diet and exercise , can produce a clinical ly meaningful reduction in bodyweight and improve HbA1c and a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas OBJECTIVE To compare and assess the single and joint effect of diet and exercise intervention for 1 year on insulin resistance and the development leading toward the insulin resistance syndrome . RESEARCH DESIGN AND METHODS An unmasked , r and omized 2 × 2 factorial intervention trial was applied with a duration of 1 year for each participant . The trial comprised 219 men and women with diastolic blood pressure of 86–99 mmHg , HDL cholesterol < 1.20 mmol/l , triglycerides > 1.4 mmol/l , total cholesterol of 5.20–7.74 mmol/l , and BMI > 24 kg/m2 . Participants were r and omly allocated to diet group ( n = 35 ) , diet and exercise group ( n = 67 ) , exercise group ( n = 54 ) , and control group ( n = 43 ) . The diet included increased intake of fish and reduced total fat intake . The exercise program entailed supervised endurance exercise three times a week . Baseline cross-sectional changes and 1-year changes in insulin resistance , fasting serum levels of insulin , C-peptide , proinsulin , glucose , and lipids as well as weight , mean blood pressure , and plasminogen activator inhibitor 1 ( PAI-1 ) values were recorded . RESULTS The cross-sectional results at baseline showed significant correlations between the calculated insulin resistance and BMI ( r = 0.54 ) and correlations between the mean blood pressure ( mBP ) ( r = 0.26 ) and PAI-1 ( r = 0.40 ) . The 1-year diet intervention gave a significant decrease in the calculated insulin resistance from 4.6 to 4.2 and a positive correlation between the changes in insulin resistance and changes in BMI ( r = 0.40 ) . The diet and exercise intervention also led to significantly decreased insulin resistance ( from 5.0 to 4.0 ) . The exercise intervention did not significantly change insulin resistance . CONCLUSIONS The cross-sectional and 1-year intervention results supported each other and underscored the important connection between increased BMI and the development leading toward the insulin resistance syndrome OBJECTIVE The objective of this study is to assess the effects of sibutramine on body weight , body fat distribution , insulin resistance , plasma leptin , lipid profile and blood pressure profiles in hypertensive obese patients . METHODS Eighty-six central obese hypertensive patients ( BMI = 39 + /- 5 kg/m(2 ) , 84 % of women , 48 + /- 8.5 years old ) were placed on a hypocaloric diet and placebo therapy for 4 weeks . They were then r and omized to receive sibutramine ( 10 mg ) or placebo for 24 weeks . Both , before therapy and at the end of the study , the waist and hip circumferences were measured and the waist/hip ratio ( WHR ) was calculated ; abdominal ultrasonography was performed in order to estimate the amount of subcutaneous fat ( SF ) and visceral fat ( VF ) , and the visceral/subcutaneous ratio . Beyond HOMA-r , another insulin resistance index ( IRIp ) was calculated by means of the formula : peak of blood glucose after oral glucose load x plasma insulin level/10(4 ) . Fasting plasma leptin and lipid levels were also determined . RESULTS Sibutramine induced greater weight reduction than placebo ( 6.7 vs. 2.5 % , p < 0.001 ) . Reductions in WHR ( 0.97 + /- 0.08 vs. 0.94 + /- 0.07 , p < 0.01 ) , IRIp ( 0.11 + /- 0.07 vs. 0.09 + /- 0.06 mmol mu/l(2 ) ) and VF ( 6.4 + /- 2.4 - 6.0 + /- 2.4 cm , p < 0.01 ) were observed only with sibutramine . Plasma leptin decreased with placebo ( 24 + /- 15 vs. 18 + /- 10 UI/l , p < 0.01 ) , but not with sibutramine ( 18.8 + /- 8.4 vs. 18.2 + /- 13.2 UI/l ) . No clinical ly significant change in lipid profile was observed in both groups . Moreover , office and 24-h blood pressure values did not change during placebo or sibutramine therapy , whereas a significant increase in office heart rate , from 78.3 + /- 7.3 - 82 + /- 7.9 b.p.m . , p = 0.02 , was observed with sibutramine . CONCLUSIONS Sibutramine therapy induced greater body weight loss than placebo in hypertensive obese patients . This was associated with WHR reduction , decreases in VF and insulin resistance . The maintenance of leptin levels during sibutramine therapy may be important to avoid weight recovery , although this finding must be confirmed by other prospect i ve studies BACKGROUND We undertook a r and omised controlled trial to assess the efficacy and tolerance of orlistat , a gastrointestinal lipase inhibitor , in promoting weight loss and preventing weight regain in obese patients over a 2-year period . METHODS 743 patients ( body-mass index 28 - 47 kg/m2 ) , recruited at 15 European centres , entered a 4-week , single-blind , placebo lead-in period on a slightly hypocaloric diet ( 600 kcal/day deficit ) . 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg ( three times a day ) or placebo for 1 year in conjunction with the hypocaloric diet . In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance ( eucaloric ) diet . FINDINGS From the start of lead-in to the end of year 1 , the orlistat group lost , on average , more bodyweight than the placebo group ( 10.2 % [ 10.3 kg ] vs 6.1 % [ 6.1 kg ] ; LSM difference 3.9 kg [ p < 0.001 ] from r and omisation to the end of year 1 ) . During year 2 , patients who continued with orlistat regained , on average , half as much weight as those patients switched to placebo ( p < 0.001 ) . Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2 , compared with a mean regain of 2.5 kg in patients who continued on placebo ( p < 0.001 ) . Total cholesterol , low-density lipoprotein ( LDL ) cholesterol , LDL/high-density lipoprotein ratio , and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group . Gastrointestinal adverse events were more common in the orlistat group . Other adverse symptoms occurred at a similar frequency during both treatments . INTERPRETATION Orlistat taken with an appropriate diet promotes clinical ly significant weight loss and reduces weight regain in obese patients over a 2-year period . The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events BACKGROUND Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk , but whether these benefits persist over time is unknown . METHODS The prospect i ve , controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched , conventionally treated obese control subjects . We now report follow-up data for subjects ( mean age , 48 years ; mean body-mass index , 41 ) who had been enrolled for at least 2 years ( 4047 subjects ) or 10 years ( 1703 subjects ) before the analysis ( January 1 , 2004 ) . The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years . RESULTS After two years , the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group ( P<0.001 ) . After 10 years , the weight had increased by 1.6 percent and decreased by 16.1 percent , respectively ( P<0.001 ) . Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period . Two- and 10-year rates of recovery from diabetes , hypertriglyceridemia , low levels of high-density lipoprotein cholesterol , hypertension , and hyperuricemia were more favorable in the surgery group than in the control group , whereas recovery from hypercholesterolemia did not differ between the groups . The surgery group had lower 2- and 10-year incidence rates of diabetes , hypertriglyceridemia , and hyperuricemia than the control group ; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable . CONCLUSIONS As compared with conventional therapy , bariatric surgery appears to be a viable option for the treatment of severe obesity , result ing in long-term weight loss , improved lifestyle , and , except for hypercholesterolemia , amelioration in risk factors that were elevated at baseline BACKGROUND Increasing concern over long-term drug treatment of mild hypertension has stimulated several studies of weight reduction . Phase I of the Trial of Antihypertensive Interventions and Management demonstrated a short-term effect of weight loss on blood pressure control in overweight persons with mild hypertension , who were either taking placebo or taking low-dose monotherapy . Phase II investigates the long-term benefit of weight loss on the ability to maintain blood pressure control . METHODS From 10148 community-based screenees , 587 persons ( 5.8 % ) , aged 21 to 65 years , entered a multicenter , r and omized drug ( double-blind , placebo-controlled ) and diet trial . Participants had a diastolic blood pressure between 90 and 100 mm Hg and were at 110 % to 160 % of their ideal weight . They were r and omized to a usual diet ( n = 296 ) or to a weight loss diet ( n = 291 ) and within each diet group to placebo , chlorthalidone , 25 mg/d , or atenolol , 50 mg/d . Treatment failure was defined as using additional antihypertensive medications if diastolic blood pressure rose above 90 mm Hg according to protocol -specified criteria . RESULTS At baseline , mean diastolic blood pressure was 93 mm Hg ; systolic blood pressure , 143 mm Hg ; weight , 88 kg ; percent ideal weight , 137 % ; age , 48 years ; 56 % were men ; and 33 % were black . Mean follow-up was 4.5 years . There was a net loss of 2 to 3 kg with weight loss diet compared with usual diet over most of the follow-up period . The 5-year incidence of treatment failure was 56.7 per 100 participants with usual diet and 49.8 per 100 with weight loss . Long-term weight loss decreased failure of blood pressure control for those receiving placebo or low-dose diuretic or beta-blocker by 23 % . The results were similar in direction in each drug group . CONCLUSIONS The Trial of Antihypertensive Interventions and Management demonstrated that weight reduction is an effective long-term therapy for maintaining blood pressure in the normal range when used as monotherapy or in combination with either thiazide diuretics or beta-blockers . Consequently , weight loss should be recommended for the management of obese individuals with mild hypertension The effect of dietary modification on continued blood pressure control after discontinuation of antihypertensive therapy has been studied . Participants who had been treated for 5 years in the Hypertension Detection and Follow-up Program were enrolled and r and omly assigned to continue medication , discontinue medication with no dietary intervention , discontinue medication and reduce weight , discontinue medication and reduce sodium groups . Relapse of hypertension was slow , even without dietary modification . Both weight loss and sodium restriction slowed relapse . The severity of the hypertension and the number of drugs required for hypertension control had a marked effect on the rate of relapse . Relapse was slowest in the participants who had attained the lowest blood pressure on therapy The purpose of this study was to investigate the effect of 1-year diet intervention , exercise intervention and both combined on blood pressure ( BP ) in normotensives and mild hypertensives . Two hundred and nineteen sedentary middle aged men and women with slightly deranged coronary heart disease ( CHD ) risk factors were r and omised to a control , a diet , an exercise and a diet + exercise group . Based on baseline diastolic BP , participants were divided into tertiles , giving baseline average BP of 141.4/96.7 in tertile 1 , 130.7/87.6 in tertile 2 and 121.9/79.0 in tertile 3 . The 1-year net-difference in BP between the intervention groups and the control group decreased across the tertiles ; in tertile 1 being -11.2/-6.7 ( p < 0.05 ) , -11.3/-6.7 ( p < 0.05 for systolic BP only ) and -7.0/-5.1 ( NS ) in the combined , diet and exercise group respectively . Triglycerides , HDL cholesterol , and insulin variables were significantly and favourably changed , the changes being most marked in the combined group . The results show that diet and diet + exercise are about equally effective in reducing BP , and the effects may be dependent on the baseline level . Within the upper tertile of baseline BP , the decline in BP in the combined intervention and the diet group are almost comparable to those obtained with drug treatment . In addition , other important CHD risk factors were all changed in a beneficial direction Objective To investigate the hypothesis that weight reduction with orlistat plus mild caloric restriction leads to better blood pressure control than diet alone in obese individuals with inadequately controlled hypertension . Design This was a 1-year , prospect i ve , r and omized , double-blind , placebo-controlled , multicenter trial of orlistat plus diet versus placebo plus diet in obese hypertensives . Interventions Participants were r and omized to receive either orlistat or placebo ; all received a 600 kcal deficient diet with no more than 30 % of calories from fat . Weight and blood pressure , lipid levels and fasting glucose and insulin levels were followed . Main outcome measures Patients on orlistat experienced greater weight loss ( −5.4 ± 6.4 versus −2.7 ± 6.4 kg , P < 0.001 ) and greater reduction in body mass index ( −1.9 ± 2.3 versus −0.9 ± 2.2 kg/m2 , P < 0.001 ) . Target weight loss , defined as ⩾ 5 % body weight ( BW ) , was obtained in more orlistat-treated patients than in the placebo group ( 46 versus 23 % , P < 0.001 ) . Diastolic BP decreased more in orlistat-treated patients than in the placebo group ( −11.4 ± 8.3 versus −9.2 ± 8.4 mmHg , P = 0.002 ) . A greater percentage of orlistat-treated patients reached goal diastolic blood pressure ( BP ) , defined as final diastolic BP < 90 mmHg or a reduction of at least 10 mmHg ( 67 versus 53 % , P < 0.001 ) . The orlistat-treated group had significantly greater reductions in total cholesterol ( P < 0.001 ) , low-density lipoprotein cholesterol ( P = 0.001 ) and non-high-density lipoprotein cholesterol ( P < 0.005 ) and target 30 % cardiovascular risk reduction was obtained in more orlistat-treated patients ( 36.1 versus 24.0 % , P < 0.04 ) . Conclusion A weight-loss program with orlistat is more effective than diet alone to lower blood pressure and results in greater cardiovascular risk reduction The possibility exists that dietary modification may increase the number of patients who remain normotensive after drug withdrawal . In an effort to resolve this question , former Hypertension Detection and Follow-up Program Stepped Care participants ( n = 496 ) were r and omized into four major groups at the end of the programme ( greater than 5 years antihypertensive therapy ) : controls ( continue medication ) ; discontinue medication , no dietary intervention ; discontinue medication and weight loss ; discontinue medication and reduce sodium . Groups 1 , 2 and 4 were further divided into obese ( greater than or equal to 120 % ideal weight , and non-obese groups ) . The weight reduction group ( greater than or equal to 120 % ideal weight ) lost 10.1 + /- 11 lbs without changing dietary sodium ( n = 87 ) . The sodium restriction group reduced urine sodium excretion from 145 to 97 mEq per day ( n = 169 ) . Sixty per cent of the weight loss group were normotensive at 56 weeks compared to 35 % withdrawn from medication without dietary intervention . The highest 56 weeks success rates were in the mild non-overweight hypertensives on sodium restriction ( 78 % ) , and the mild overweight hypertensives on weight reduction ( 72 % ) . R and omization to either weight loss group or sodium restriction group increased the likelihood of remaining off drugs ( adjusted odds ratio of 3.43 for the weight group and 2.17 for the sodium group ( P less than 0.05 ) . Age , severe hypertension greater than 5 years previous to entry into Dietary Intervention Study of Hypertension ( DISH ) or need for several drugs increased the chance of failure This report examines the effect of weight loss , alone and in combination with drugs , on diastolic blood pressure change in the Trial of Antihypertensive Interventions and Management ( T AIM ) , which is a r and omized , multicenter , placebo-controlled clinical trial of drug and diet combinations in the treatment of mild hypertension among 787 patients . Diastolic blood pressure drop ( 11.6 mm Hg ) at 6 months among those patients who were r and omized to weight reduction and placebo drug treatment was greater among those who lost 4.5 kg or more , than the 7-mm Hg drop for those who lost less than 2.25 kg or for the placebo-treated control group , and it was statistically equivalent to the reduction achieved by 25 mg of chlorthalidone or 50 mg of atenolol ( 11.1- and 12.4-mm Hg drop , respectively ) . Weight loss potentiated effects of drugs , with reductions of 18.4 mm Hg , for those patients who were taking atenolol and had a 4.5-kg or more weight loss , and of 15.4 mm Hg , for those patients who were taking chlorthalidone and had at least a 2.25-kg weight loss . We concluded that effective weight loss ( greater than or equal to 4.5 kg ) lowers blood pressure similarly to low-dose drug therapy and potentiates drug effects , with the apparent 4.5-kg threshold being lowered to 2.25 kg for those patients who receive chlorthalidone In the Oslo Diet and Exercise Study ( ODES ) 219 healthy middle-aged physically inactive persons with moderately deranged risk factor levels ( increased bodyweight , diastolic blood pressure , serum cholesterol , triglycerides , decreased HDL-cholesterol ) were r and omized to 4 intervention groups : dietary intervention , exercise , diet + exercise and control . The purpose of the study was to test if these interventions maintained for a year , isolated or in combination , would change coronary risk factor levels as compared to control . One of the risk factors included was lipoprotein ( a ) ( Lp(a ) ) . The hypothesis to be tested was if physical exercise would be associated with increased levels of Lp(a ) as a result of intervention . Those who exercised increased their Lp(a ) levels with 15.4 ( S.E. = 8.0 ) mg/l as compared to no exercise ( P < 0.05 ) . Also , dietary intervention tended to increase Lp(a ) , but the increase did not reach statistical significance . There was no detectable interaction on the effect on Lp(a ) of the two intervention modalities . A dose-response relationship was found between change in the exercise-specific variables heart rate and peak oxygen uptake , and Lp(a)-change and this dose-response was most pronounced in the exercise group . Change in Lp(a ) was associated to change in several lifestyle related variables such as alcohol intake and waist circumference , pointing to the possibility that Lp(a ) , at least in some sub population s , is more amenable to change through lifestyle alterations than reported so far The Trial of Antihypertensive Intervention and Management evaluated nine diet-drug combinations in 878 mildly hypertensive , moderately obese participants using a 3 x 3 factorial design . Drugs evaluated were placebo , diuretic ( chlorthalidone ) , and beta-blocker ( atenolol ) ; diets were usual ( no intervention ) , weight reduction , and low sodium/high potassium ( Na/K ) . This article reports 6-month dietary changes and the effect of dietary change on blood pressure . Six-month mean weight change was -4.7 kg in the weight reduction group , -0.3 kg in the Na/K group , and -0.5 kg in the usual-diet group . At 6 months , daily electrolyte excretion had changed in the Na/K intervention group . Daily sodium excretion decreased from 138.0 to 112.0 mmol in the Na/K group and increased from 134.1 to 138.4 mmol in the weight reduction group and from 129.1 to 137.0 mmol in the usual-diet group . Daily potassium output increased from 58.7 to 71.4 mmol in the Na/K group , from 57.0 to 60.5 mmol in the weight reduction group , and from 55.3 to 59.1 mmol in the usual diet group . Analysis of 3-day food records indicated that sodium intake decreased from 141.1 to 85.8 mmol and potassium intake increased from 76.4 to 90.5 mmol . Our results indicate that the goal for weight reduction was more easily achieved than the goal for electrolyte modification |
12,492 | 26,168,085 | Conclusions : With the possible exception of rice , existing evidence suggests that GI values do not differ when measured in Caucasians versus non-Caucasians . | Objectives : Low glycaemic index ( GI ) foods are recommended to improve glycaemic control in diabetes ; however , Health Canada considers that GI food labeling would be misleading and unhelpful , in part , because selected studies suggest that GI values are inaccurate due to an effect of ethnicity .
Therefore , we conducted a systematic review and meta- analysis to compare the GI of foods when measured in Caucasians versus non-Caucasians . | 1 . The degree to which disruption by mastication affects the glycaemic response to four different carbohydrate foods was investigated in healthy human volunteers ; each food was eaten by six subjects . 2 . Subjects ate meals of sweetcorn , white rice , diced apple or potato on two occasions ; on one occasion they chewed the food thoroughly , on the other occasion they swallowed each mouthful without chewing it . 3 . When the foods were chewed the postpr and ial blood glucose levels rose to levels which varied according to the food ingested . 4 . Swallowing without chewing reduced the glycaemic response to each food , achieving a similar effect as administration of viscous polysaccharides or ' slow-release ' carbohydrates The determine the effect of different foods on the blood glucose , 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers . Blood glucose levels were measured over 2 h , and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose . The largest rises were seen with vegetables ( 70 + /- 5 % ) , followed by breakfast cereals ( 65 + /- 5 % ) , cereals and biscuits ( 60 + /- 3 % ) , fruit ( 50 + /- 5 % ) , dairy products ( 35 + /- 1 % ) , and dried legumes ( 31 + /- 3 % ) . A significant negative relationship was seen between fat ( p less than 0.01 ) and protein ( p less than 0.001 ) and postpr and ial glucose rise but not with fiber or sugar content The glycaemic index ( GI ) concept was originally introduced to classify different sources of carbohydrate (CHO)-rich foods , usually having an energy content of > 80 % from CHO , to their effect on post-meal glycaemia . It was assumed to apply to foods that primarily deliver available CHO , causing hyperglycaemia . Low-GI foods were classified as being digested and absorbed slowly and high-GI foods as being rapidly digested and absorbed , result ing in different glycaemic responses . Low-GI foods were found to induce benefits on certain risk factors for CVD and diabetes . Accordingly it has been proposed that GI classification of foods and drinks could be useful to help consumers make ' healthy food choices ' within specific food groups . Classification of foods according to their impact on blood glucose responses requires a st and ardised way of measuring such responses . The present review discusses the most relevant method ological considerations and highlights specific recommendations regarding number of subjects , sex , subject status , inclusion and exclusion criteria , pre-test conditions , CHO test dose , blood sampling procedures , sampling times , test r and omisation and calculation of glycaemic response area under the curve . All together , these technical recommendations will help to implement or reinforce measurement of GI in laboratories and help to ensure quality of results . Since there is current international interest in alternative ways of expressing glycaemic responses to foods , some of these methods are discussed The glycemic response ( GR ) to food is influenced by both intrinsic and extrinsic factors . A consistent observation in GR studies is the wide within- and between-individual variations . The authors hypothesize that between-individual variations in the GR , insulin response ( IR ) and gastric emptying occur even when food particle size is st and ardized . Volunteers were tested on 2 nonconsecutive days after an overnight fast in r and omized order . On 1 day , the volunteers consumed large ( > 2000 μm ) rice particles , and on the second day , small rice particles ( 500 - 1000 μm ) . Subsequently , gastric emptying using the sodium [ (13)C ] acetate breath test ( for 240 minutes ) and GR and IR ( for 120 minutes ) from finger-prick blood sample s were measured . The incremental area under the curve ( IAUC ) for the GR for small particles varied 45 % more compared with whole rice . The small particles elicited a significantly greater GR IAUC than the large particles . The st and ard deviations associated with the IR IAUC for the small particles was 140 % greater than that of the large particles . The total IAUC for IR was also significantly greater for the small particles than the large particles . The between-individual variations associated with gastric emptying times were similar for both sample s. The gastric emptying latency phase , lag , and half time were significantly shorter for the small particles . Ingesting small particles causes faster gastric emptying and produces greater glycemic and IRs . Between-individual variations in GR and IR can be observed even when all the food associated factors including ingested particle size ( mastication ) are controlled for in humans To determine the influence of masticatory efficiency on postpr and ial satiety and glycaemic response , twenty-one healthy males were recruited for this r and omised cross-over trial . The participants consumed a fixed amount of pizza provided in equal-sized portions by chewing each portion either fifteen or forty times before swallowing . Subjective appetite was measured by appetite question naires at regular intervals for 3 h after the meal and plasma sample s were collected for the measurement of selected satiety-related hormones , glucose , insulin and glucose-dependent insulinotropic peptide ( GIP ) concentrations . An ad libitum meal was provided shortly after the last blood sample was drawn and the amount eaten recorded . Compared with fifteen chews , chewing forty times per portion result ed in lower hunger ( P= 0·009 ) , preoccupation with food ( P= 0·005 ) and desire to eat ( P= 0·002 ) . Meanwhile , plasma concentrations of glucose ( P= 0·024 ) , insulin ( P < 0·001 ) and GIP ( P < 0·001 ) were higher following the forty-chews meal . Chewing forty times before swallowing also result ed in a higher plasma cholecystokinin concentration ( P= 0·045 ) and a trend towards a lower ghrelin concentration ( P= 0·051 ) . However , food intake at the subsequent test meal did not differ ( P= 0·851 ) . The results suggest that a higher number of masticatory cycles before swallowing may provide beneficial effects on satiety and facilitate glucose absorption Objective : To determine and compare the glycaemic index ( GI ) values of a range of Vietnamese foods in two racial groups . Design and subjects : Twelve healthy subjects ( six Asian and six Caucasian ) consumed 50 g carbohydrate portions of a reference food ( glucose sugar ) and nine Vietnamese foods ( three rices , three noodle products and three sweet foods ) in r and om order after an overnight fast . The reference food was tested on two separate occasions , and the Vietnamese foods were each tested once . Capillary blood sample s were taken at time 0 ( fasting ) , 15 , 30 , 45 , 60 , 90 and 120 min from the start of each meal . Sample s were analysed for plasma glucose and the incremental areas under the plasma glucose curves ( AUC ) were used to calculate the GI values of the test foods , using glucose as the reference food ( ie GI value of glucose=100 ) . The mean GI value of each food was calculated for the entire group of subjects ( n=12 ) and for both racial groups ( n=6 ) . Results : The three rices had surprisingly high GI values ( 86–109 ) , whereas the noodle products had relatively low GI values ( 39–61 ) . The sugar-rich foods produced intermediate GI values ( 54–79 ) . The GI values for the nine foods calculated separately for the two racial groups were not significantly different from each other ( P=0.26 ) . Conclusions : The GI values derived from Caucasian subjects are likely to be applicable to Asian population s. Varieties of imported rice from Thail and were found to have high GI values . Alternative low-GI staples , such as rice noodles , may be preferable for Asian/Vietnamese people with diabetes . Sponsorship : This study was funded by the University of Sydney . European Journal of Clinical Nutrition ( 2001 ) 55 , Background Glycemic index ( GI ) is intended to be a property of food but some reports are suggestive that GI is influenced by participant characteristics when glucose is used as a reference . Objective To examine the influence of different reference foods on observed GI . Design The GIs of five varieties of rice and a sugary beverage ( LoGiCane ™ ) were tested in 31 European and 32 Chinese participants using glucose or jasmine rice as reference foods . The GIs of two ready-to-eat breakfast cereals ( Kellogg ’s cornflakes and Sustain ) were tested in 20 younger and 60 older people using glucose or Sustain as reference foods . Results The GIs of rice tended to be higher in the Chinese compared with the Europeans when glucose was used as a reference ( jasmine 80 vs 68 , P = 0.033 ; basmati 67 vs 57 , P = 0.170 ; brown 78 vs 65 , P = 0.054 ; Doongara 67 vs 55 , P = 0.045 ; parboiled 72 vs 57 , P = 0.011 ) . There were no between-group differences in GI when jasmine rice was the reference . The GIs of breakfast cereals tended to be lower in younger compared with older groups ( cornflakes 64 vs 81 , P = 0.008 ; Sustain 56 vs 66 , P = 0.054 ) . There was no between-group difference in the GI of cornflakes when Sustain was the reference ( cornflakes 115 vs 120 , P = 0.64 ) . There was no ethnic difference in GI when glucose was the reference for another sugary food ( LoGiCane ™ 60 vs 62 ; P = 0.69 ) . Conclusions A starchy reference may be more appropriate than a glucose beverage when attempting to derive universally applicable GI values of starchy foods . Trial registration The Chinese/European trial is registered with the Australian New Zeal and Clinical Trials Registry as ACTRN12612000519853 Coffee and tea may influence glycaemic responses but it is not clear whether they affect the glycaemic index ( GI ) value of foods . Therefore , to see if coffee and tea affected the mean and SEM of GI values , the GI of fruit leather ( FL ) and cheese puffs ( CP ) were determined twice in ten subjects using the FAO/WHO protocol with white bread as the reference food . In one series subjects chose to drink 250 ml of either coffee or tea with all test meals , while in the other series they drank 250 ml water . The tests for both series were conducted as a single experiment with the order of all tests being r and omised . Coffee and tea increased the overall mean peak blood glucose increment compared with water by 0.25 ( SEM 0.09 ) mmol/l ( P=0.02 ) , but did not significantly affect the incremental area under the glucose response curve . Mean GI values were not affected by coffee or tea but the SEM was reduced by about 30 % ( FL : 31 ( SEM 4 ) v. 35 ( SEM 7 ) and CP : 76 ( SEM 6 ) v. 75 ( SEM 8) for coffee or tea v. water , respectively ) . The error mean square term from the ANOVA of the GI values was significantly smaller for coffee or tea v. water ( F(18 , 18 ) = 2.31 ; P=0.04 ) . We conclude that drinking coffee or tea with test meals does not affect the mean GI value obtained , but may reduce variability and , hence , improve precision We studied 12 subjects with diabetes to determine how well the glycemic index ( Gl ) predicted the ranking of glycemic responses of different foods in individuals . All subjects ate three mixed meals ( bread , rice , or spaghetti with GIs of 100 , 79 , and 61 , respectively ) four times in a r and omized complete block design . The mean glycemic response areas of the different meals ranked according to the predicted Gl in every individual . The observed mean ± SD Gl values of the meals were significantly different from each other ( bread 100 ± 7 , rice 75 ± 9 , spaghetti 54 ± 9 ) , with no significant difference in response between subjects . It is concluded that individuals share common mean Gl values for different foods . Within confidence limits determined by the variability of glycemic responses , the number of repeated tests conducted , and the expected Gl difference , the Gl can be used to predict the ranking of the mean glycemic responses of mixed meals taken by individuals Consumption of a low glycemic index ( GI ) diet may be helpful in the management and prevention of diabetes and cardiovascular disease . The investigation of GI has been predominantly confined to white subjects . We hypothesized that differences in glycemic response ( GR ) may be observable in subjects of different ethnic origin . The objective of the present study was to determine GR to a high GI ( glucose ) and low GI ( maltitol ) test drink in subjects of different ethnic origin . In a r and omized , single-blind crossover trial , 10 whites , 10 South Indians and 10 Chinese subjects consumed either glucose or maltitol test drink containing 50 g of one of the test products on different occasions . Capillary blood glucose sample s were taken at 15 and 10 minutes before and 0 , 15 , 30 , 45 , 60 , 90 , 120 , 150 , and 180 minutes after consumption of the test drink . The incremental area under the curve of glucose and maltitol were not significantly different between the 3 groups . The mean GR for maltitol was 33.5 % in whites , 32.9 % in Chinese , and 23.1 % in South Indians . The results presented here confirmed that there are no observable differences noted in GR to a high-GI or low-GI test drink between the 3 ethnically diverse groups . We conclude that different ethnic groups exhibit similar GR to low- and high-GI drinks , and GR to maltitol is similar irrespective of ethnic background |
12,493 | 18,384,479 | Although HIV has been shown to affect all domains of child functioning , motor development is the most apparent in terms of severity , early onset , and persistence across age groups . | OBJECTIVE To determine the degree of motor , cognitive , language and social-emotional impairment related to HIV infection in children living in sub-Saharan Africa ( SSA ) . | Objectives . To compare language development in infants and young children with human immunodeficiency virus ( HIV ) infection to language development in children who had been exposed to HIV but were uninfected , and ( among subjects with HIV infection ) to compare language development with cognitive and neurologic status . Design . Prospect i ve evaluation of language development in infected and in exposed but uninfected infants and young children . Setting . Pediatric Infectious Disease Clinic , State University of New York – Health Science Center at Syracuse . Subjects . Nine infants and young children infected with HIV and 69 seropositive but uninfected infants and children , age 6 weeks to 45 months . Results . Mean Early Language Milestone Scale , 2nd edition ( ELM-2 ) Global Language scores were significantly lower for subjects with HIV infection , compared with uninfected subjects ( 89.3 vs 96.2 , Mann – Whitney U test ) . The proportion of subjects scoring > 2 SD below the mean on the ELM-2 on at least one occasion also was significantly greater for subjects with HIV infection , compared with uninfected subjects ( 4 of 9 infected subjects , but only 5 of 69 uninfected subjects ; Fisher 's exact test ) . Seven of the 9 subjects with HIV infection manifested deterioration of language function . Four manifested unremitting deterioration ; only 1 of these 4 demonstrated unequivocal abnormality on neurologic examination . Three subjects with HIV infection and language deterioration showed improvement in language almost immediately after the initiation of antiretroviral drug treatment . Magnetic resonance imaging or computed tomography of the brain were performed in 6 of 7 infected subjects with language deterioration , and findings were normal in all 6 . ELM-2 Global Language scaled scores showed good agreement with the Bayley Mental Developmental Index or the McCarthy Global Cognitive Index ( r = 0.70 ) . Language deterioration , or improvement in language after initiation of drug therapy , coincided with or preceded changes in global cognitive function , at times by intervals of up to 12 months . Conclusions . Language deterioration occurs commonly in infants and young children with HIV infection , is seen frequently in the absence of abnormalities on neurologic examination or central nervous system imaging , and may precede evidence of deterioration in global cognitive ability . Periodic assessment of language development should be added to the developmental monitoring of infants and young children with HIV infection as a means of monitoring disease progression and the efficacy of drug treatment BACKGROUND The neurodevelopmental outcomes of human immunodeficiency virus type 1 (HIV-1)-infected Ug and an infants of nondrug-using mothers were studied using controlled , prospect i ve methodology . METHOD The sample of 436 full-term infants included 79 HIV-infected infants of HIV-1-infected mothers , 241 uninfected infants of HIV-1-infected mothers ( seroreverters ) , and 116 uninfected infants born to HIV-negative mothers . Neurologic status , information processing ability , and motor and mental development were assessed from 6 to 24 months of age . Observations of caretaker-child interaction and home environments were made at 6 and 12 months . All evaluators were blinded to the HIV status of the child and family . RESULTS Compared with seroreverters and uninfected infants , HIV-infected infants demonstrated greater deficits in motor development and neurologic status , and more frequent and earlier onset of motor and neurologic abnormalities . Compared with controls , HIV-infected infants had more abnormalities in mental development at 6 and 18 months and an earlier onset of abnormalities . By 12 months , 30 % of HIV-infected infants demonstrated motor abnormalities and 26 % cognitive abnormalities as compared with 11 % and 6 % among seroreverters and 5 % and 6 % among seronegative infants . HIV-infected infants ( 62 % ) demonstrated a higher probability of developing an abnormal neurologic examination by 12 months , compared with seroreverters ( 17 % ) or seronegative infants ( 15 % ) . Information-processing abilities did not differ as a function of HIV infection . Home environments and infants ' interactions with caretakers were similar across groups . CONCLUSION We conclude that HIV infection results in more frequent and earlier abnormalities in infants ' neurologic status and motor development that are not attributable to other biological and environmental risk factors . More frequent mental developmental abnormalities were evident at several ages . However , information-processing abilities , such as recognition memory , may be spared from HIV-related deficits Objective . To examine the frequency , timing , and factors associated with abnormal cognitive and motor development during the first 30 months of life in infants born to women infected with human immunodeficiency virus type 1 ( HIV-1 ) . Methods . Serial neurodevelopmental assessment was performed with 595 infants born to women infected with HIV-1 in a multicenter , prospect i ve , natural history cohort study . Survival analysis methods were used to evaluate 6 outcome events related to abnormal cognitive and motor growth ( time to confirmed drop of 1 SD , time to first score < 69 , and time to confirmed drop of 2 SD ) in Bayley Scales of Infant Development Mental Developmental Index ( MDI ) and Psychomotor Developmental Index ( PDI ) scores among infected ( n = 114 ) and uninfected ( n = 481 ) infants . Proportional hazards modeling was used to evaluate the effects of HIV infection status , prematurity , prenatal exposure to illicit drugs , maternal educational attainment , and primary language . Results . HIV-1 infection was significantly associated with increased risk for all outcome events related to abnormal mental and motor growth . Differences between infected and uninfected infants were apparent by 4 months of age . Prematurity was associated with increased risk for MDI < 69 and PDI < 69 . Maternal education of < 9 completed years was associated with increased risk for MDI < 69 . Neither prenatal exposure to illicit drugs nor primary language other than English was associated with abnormal development . Conclusion . A significant proportion of infants with HIV-1 infection show early and marked cognitive and motor delays or declines that may be important early indicators of HIV disease progression . These abnormalities are independent of other risk factors for developmental delay BACKGROUND HIV contributes substantially to child mortality , but factors underlying these deaths are inadequately described . With individual data from seven r and omised mother-to-child transmission ( MTCT ) intervention trials , we estimate mortality in African children born to HIV-infected mothers and analyse selected risk factors . METHODS Early HIV infection was defined as a positive HIV-PCR test before 4 weeks of age ; and late infection by a negative PCR test at or after 4 weeks of age , followed by a positive test . Mortality rate was expressed per 1000 child-years . We investigated the effect of maternal health , infant HIV infection , feeding practice s , and age at acquisition of infection on mortality assessed with Cox proportional hazards models , and allowed for r and om effects for trials grouped geographically . FINDINGS 378 ( 11 % ) of 3468 children died . By age 1 year , an estimated 35.2 % infected and 4.9 % uninfected children will have died ; by 2 years of age , 52.5 % and 7.6 % will have died , respectively . Mortality varied by geographical region , and was associated with maternal death ( adjusted odds ratio 2.27 , 95 % CI 1.62 - 3.19 ) , CD4 + cell counts < 200 per microL ( 1.91 , 1.39 - 2.62 ) , and infant HIV infection ( 8.16 , 6.43 - 10.33 ) . Mortality was not associated with either ever breastfeeding and never breastfeeding in either infected or uninfected children . In infected children , mortality was significantly lower for those with late infection than those with early infection ( 0.52 , 0.39 - 0.70 ) . This effect was also seen in analyses of survival from the age at infection ( 0.74 , 0.55 - 0.99 ) . INTERPRETATION These findings highlight the necessity for timely antiretroviral care , for support for HIV-infected women and children in developing countries , and for assessment of prophylactic programmes to prevent MTCT , including child mortality and infection averted BACKGROUND Combination therapy including protease inhibitors has been shown to be effective in treating adults infected with human immunodeficiency virus type 1 ( HIV-1 ) , but there are only limited data regarding the treatment of children and adolescents . METHODS A cohort of 1028 HIV-1-infected children and adolescents , from birth through 20 years of age , who were enrolled in research clinics in the United States before 1996 was followed prospect ively through 1999 . We used proportional-hazards regression models to estimate the effect on mortality of combination therapy including protease inhibitors . RESULTS Seven percent of the subjects were receiving combination therapy including protease inhibitors in 1996 ; by 1999 , 73 percent were receiving such therapy . In univariate analyses , a higher base-line percentage of lymphocytes that were CD4-positive , a higher weight for age , a higher height for age , black race , Hispanic ethnic background , younger age , and perinatally acquired infection were associated with a longer median time to the initiation of this type of therapy ( P<0.001 ) . After adjustment for covariates , the differences among racial and ethnic groups in the time to initiation were not statistically significant . Mortality declined from 5.3 percent in 1996 to 2.1 percent in 1997 , 0.9 percent in 1998 , and 0.7 percent in 1999 ( P for trend < 0.001 ) . There were reductions in mortality in all subgroups defined according to age , sex , percentage of CD4 + lymphocytes , educational level of the parent or guardian , and race or ethnic background . In adjusted analyses , the initiation of combination therapy including protease inhibitors was independently associated with reduced mortality ( hazard ratio for death , 0.33 ; 95 percent confidence interval , 0.19 to 0.58 ; P<0.001 ) . CONCLUSIONS The use of combination therapy including protease inhibitors has markedly reduced mortality among children and adolescents infected with HIV-1 Neurodevelopmental outcomes of human immunodeficiency virus Type 1 (HIV-1)-infected infants of non-drug-using mothers were assessed in a controlled , prospect i ve study from birth to 24 months with 3 groups : 61 infants of HIV-infected mothers , 234 uninfected infants of HIV-infected mothers ( seroreverters ) , and 115 uninfected infants of uninfected mothers . Compared with seroreverters and uninfected infants , HIV-infected infants demonstrated lower mental and motor development on the Bayley Scales and greater deceleration in their rate of motor development . HIV-infected infants with abnormal neurologic exams had lower motor and mental test scores and lower rates of motor Bayley Scales scores than their HIV-infected counterparts with normal neurologic exams . Contrary to prediction , no group differences in mean performance or growth rates were found on visual information processing on the Fagan Test of Infant Intelligence OBJECTIVE . The purpose of this study was to assess the health status and school-age neurodevelopmental progress of antiretroviral treatment (ARVT)–naive , HIV-infected Ug and an children who had been followed as part of cohorts of children born to HIV-infected and -noninfected mothers between 1989 and 1993 . METHODS . Twenty-eight children , aged 6 to 12 years , vertically infected with HIV-1 and never treated with ARVT were evaluated in terms of health status , neurologic , and psychometric testing . A r and omly selected group of 42 seroreverters and 37 HIV-1 negative children who were age- and gender-matched and who had been followed in the same cohorts were evaluated also . The families studied were homogenous in their socioeconomic status . None of the mothers or children had received ARVT or been exposed to illicit drugs . RESULTS . The HIV-infected children showed significantly more evidence of acute malnutrition . They also had more illness , especially parotitis , otitis media , upper respiratory infections , and lymphadenopathy . However , they did not differ significantly in neurologic and cognitive assessment s when compared with age- and gender-matched seroreverter and HIV-negative children . They were in the normal range with respect to neurologic and psychometric development measures . CONCLUSIONS .These children seem to represent a significant subgroup of HIV-infected child survivors for whom the progress of the disease is less aggressive throughout early life . Given the fact that many infants , especially in developing countries , continue to be born without the benefit of perinatal ARVT , there will likely continue to be many older HIV-infected children in the same situation as those described in this follow-up study . They will not have been recognized as being HIV-infected . It is important that such children be identified and offered access to ARVT and other appropriate support services |
12,494 | 10,908,533 | MAIN RESULTS None of the drugs ( phenmetrazine , amphetamine sulphate/ephedrine + atropine , furosemide ( sic ) or chlorprotixine ) were better than placebo during treatment .
The numbers were too small to draw reliable conclusions , and none are used in current practice in the UK .
Alarm treatment was better than drugs in one small trial .
REVIEW ER 'S CONCLUSIONS There was not enough evidence to suggest that the included drugs reduced bedwetting .
There was limited evidence to suggest that imipramine and alarms were better , and in other review s , desmopressin , tricyclics and alarm interventions have tentatively been shown to be effective | BACKGROUND Enuresis ( bedwetting ) is a socially unacceptable and stressful condition which affects around 15 - 20 % of five year olds , and up to 2 % of young adults .
Although there is a high rate of spontaneous remission , the social , emotional and psychological costs to the children can be great .
OBJECTIVES To assess the effects of drugs other than desmopressin and tricyclics on nocturnal enuresis in children , and to compare them with other interventions . | Summary The present study was partly a clinical pharmacological analysis of the action of imipramine in nocturnal enuresis and partly an attempt to select children who would benefit most from this treatment . 61 fairly severe cases of nocturnal enuresis were studied as out- patients , divided by the criteria primary / secondary enuresis and with/without associated behavioural disturbances . The patients received imipramine , imipramine-N-oxide , emepronium , and a placebo in r and om sequence in a double-blind cross-over trial . There was no difference in effect between placebo and emepronium ; after imipramine the frequency of enuresis fell to 58 % of the figure during placebo treatment , i.e. 31 % of the children became dry ; imipramine-N-oxide reduced the number of wet nights only to 78 % of the number on placebo , 18 % of the children became dry . When the patients were classified into groups imipramine and imipramine-N-oxide were found to have had the greatest effect in cases of presumed psychogenic aetiology , a 65 % reduction of the frequency of wet nights whilst taking the placebo . The most favourable results were in children with combined nocturnal and diurnal enuresis and in those with urinary frequency and imperative urgency . The effect was maintained during treatment for 3 months with the most suitable drug . The dose was 50 mg regardless of the body weight of the patient . There were no serious side effects . It was concluded that the psychopharmacological actions of imipramine and imipramine-N-oxide appear to be important in their effects on enuresis . Imipramine might have been the best drug because success may require the combination of antidepressant and anticholinergic activity . It was not possible to assess in detail its presumed effect on the level of sleep . Thus many children can be treated successfully and the final cure of enuresis may be hastened by breaking a vicious circle of psychological phenomena Purpose : The treatment approach for enuresis is controversial due to the lack of consensus as to the exact causes of nocturnal enuresis . Despite various treatment modalities , pharmacotherapy still appears to be the common choice . The aim of this prospect i ve study was the evaluation of the efficacy of combination therapy ( imipramine and oxybutynin ) in patients with enuresis nocturna . Patients and Methods : This prospect i ve study was done with 77 monosymptomatic nocturnal enuretics between July 1996 and December 1998 . Results : Even though there is no statistically significant difference between combination therapy ( imipramine plus oxybutynin ) and monotherapy , clinical data showed that combination therapy is more effective . Conclusions : We conclude that combination of imipramine with oxybutynin is a safe and new choice in the treatment of nocturnal enuresis Abstract Sixty-two children with nocturnal enuresis ( 43 boys , 19 girls aged 6–15 years ) were treated with either desmopressin ( Adiuretin-SD ) ( n=32 ) or sodium diclofenac ( n=30 ) . Desmopressin was effective in 85 % of children and diclofenac in 33 % . In children with primary nocturnal enuresis , the glomerular filtration rate was normal , whereas diuresis and solute excretion during the night were increased . Compared with healthy children , the nightly excretion of sodium was elevated by 43.7 % and magnesium by 58.4 % . A high correlation was found between the free water reabsorption and solute clearance ( P<0.001 ) in children with nocturnal enuresis . Changes in kidney function in nocturnal enuresis appear to be due to a decrease in the water and ion reabsorption in the thick ascending limb of Henle ’s loop because of a changed regulation of ion transport in this part of the nephron . Administration of desmopressin or a decrease in prostagl and in production after diclofenac administration restores the ion and water transport in the kidney , which results in the disappearance of nocturnal enuresis . The results indicate a role of changes in regulation of ion transport in renal tubules in the pathogenesis of one of the forms of primary nocturnal enuresis A double-blind clinical study of 30 boys , six to ten years of age , with primary nocturnal enuresis was undertaken to assess the role of and rogens in treating enuresis . The oral synthetic and rogen mesterolone was selected because of its minimal potential toxic effects . Twenty boys were treated with mesterolone and 10 received placebo . Fourteen boys ( 70 % ) became dry during treatment ( 20 mg daily for 14 days ) , and 5 ( 25 % ) remained dry for a follow-up period of four months . Increased cystometric bladder capacity and disappearance of uninhibited detrusor contractions were noticed in a significant number of cases after treatment . No side effects were recorded . Mesterolone has probably modulated the autonomic innervation of the vesical musculature with correction of the defective neural mechanism which is believed to be implicated in the pathogenesis of nocturnal enuresis The prostagl and in synthesis inhibitor indomethacin ( used as a suppository ) was compared to placebo in the treatment of primary nocturnal enuresis in a double-blind crossover study . There were 12 girls and 7 boys between 6 and 15 years old . Indomethacin ( 50 to 100 mg . ) was significantly more effective than placebo in the treatment of primary enuresis OBJECTIVES To compare the efficacy of desmopressin and indomethacin and also determine the prostagl and in E2 ( PGE2 ) concentrations in the patient and control groups . METHODS Eighty-five children with primary nocturnal enuresis were followed up for a baseline period of 4 weeks , during which they recorded wet and dry nights . After this period , the patients were divided into three groups that used desmopressin , indomethacin , or placebo for 4 weeks . The dosage of desmopressin ( group A , n = 31 ) was 20 microg/day and the dosage of indomethacin ( group B , n = 29 ) was 100 mg/day . The placebo group ( group C ) consisted of 25 patients . We determined the serum PGE2 and urine PGE2 concentrations before and after treatment in the three groups and in a control group . RESULTS Treatment with desmopressin and indomethacin result ed in significantly more dry nights during the 4 weeks of observation than did placebo ( P < 0.005 ) . The number of dry nights was also significantly different in the desmopressin group than in the indomethacin group ( P < 0.01 ) . In the total patient group , the mean serum and urine PGE2 concentrations were significantly different from the control group 's serum and urine PGE2 concentrations ( P < 0.001 ) . There was a significant decrease in the serum and urine PGE2 concentrations in group A and group B after the treatment period ( P < 0.01 ) . CONCLUSIONS Desmopressin and indomethacin were found to be more effective than placebo . We conclude that prostagl and ins have an important role in the pathophysiology of primary nocturnal enuresis 1 . The prostagl and in synthesis inhibitor diclofenac sodium has been compared with a placebo in the treatment of primary nocturnal enuresis in a double‐blind crossover trial Summary A study of 45 children with enuresis showed that administration of Methedrine result ed in earlier and more complete relief , compared to those on a placebo The effect of imipramine , desmethylimipramine , and methscopolamine on blood pressure ( BP ) and plasma norepinephrine ( NE ) was measured in enuretic boys in a double‐blind , placebo‐controlled study . Measurements were obtained on the thirteenth day of medication ( 75 mg at bedtime ) . The tricyclic drugs induced a rise in diastolic BP as well as an increase in plasma NE but there was no significant relationship between the increments in plasma NE and BP . The plasma concentration of drug correlated with the drug‐induced BP rise . This is the fifth study to demonstrate a hypertensive effect of tricyclic drugs in children in contrast to the systolic hypotension usually seen in adult patients . It is not clear from our data whether children have different cardiovascular compensatory reflexes or whether they experience a greater stimulant effect from the drug SUMMARY A controlled trial of conditioning by alarm and of amphetamine for the treatment of enuresis was planned . The experimental group was to consist of 118 enuretic schoolchildren of 8 years and over , detected in a community survey , but only 37 could be enrolled for the trial ; 57 had remitted spontaneously or improved before appointments could be made , 15 defaulted , and 9 were rejected as unsuitable . The 37 cases were allocated at r and om to the two treatments . Assessment s were made six months later , by which time 4 further cases had been lost to the trial . Among 33 cases remaining , 16 on alarm and 17 on amphetamine , the results for the alarm were significantly better ; this was more so among the 23 cases whose treatment was considered adequate . Amphetamine had no greater effect than the natural remission-rate . The significance of this result to theories of conditioning and of the mechanism of enuresis is discussed . RESUME Un essai de traitement par conditionnement dans Venuresie nocturne Les auteurs projetaient de comparer l'effet du conditionnement par alarme et de l'amphetamine dans le traitement de l'enuresie . A cet effet , 118 ecoliers enuretiques âges de 8 ans et au-dessus ont ete depistes au cours d'une enquete ; ils devaient constituer le groupe experimental mais 37 seulement ont pu etre enroles pour l'essai . 57 se sont dedits spontanement ou ameliores avant qu'on ait pu les convoquer , 15 ont fait defaut et 9 ont ete rejetes comme impropres a l'essai . Parmi ces 33 restant , 16 traites par alarme et 17 par l'amphetamine , les result ats obtenus par Falarme ont ete nettement meilleurs . L'effet de l'amphetamine ne depassait pas le taux de remission naturel . Les auteurs discutent la signification de ces result ats pour la theorie du conditionnement et celle du mecanisme de l'enuresie Efficacy and tolerance of the anticholinergic and calcium antagonistic drug terodiline ( Mictrol ) were investigated in comparison to placebo in 42 children with diurnal enuresis . The study was double-blind with a modified cross-over design with 2 treatment periods of 4 weeks . Terodiline in a daily dose of 25 mg was well tolerated . A statistically significant decrease in the number of wet episodes per day was found with terodiline when compared to placebo . In addition a high patient preference for terodiline was observed . This study shows that terodiline is effective in the treatment of daytime enuresis in children . The low incidence of side-effects also favours the use of terodiline in children A double-blind study of terodiline compared with placebo was performed in 58 children aged 6 to 14 years with urgency or urge incontinence . All had an unstable bladder at cystometry . A bladder regimen was emphasised during the study . Continence was improved according to micturition charting and a pad test in both groups . Terodiline at 25 mg/day , however , gave significantly better results than placebo . In patients with a subnormal bladder capacity ( less than or equal to 150 ml ) , a significant increase in capacity was recorded on cystometry during medication with terodiline but not with placebo . The improved continence seen in the placebo group was probably due to the non-specific bladder training achieved by the child 's increased awareness and adult involvement during treatment . The even better results attained in the terodiline group shows this drug to be a valuable adjunct to a bladder regimen in children with urge incontinence , particularly since no important adverse effects were noted during an 8-week period The efficacy of treatment with imipramine hydrochloride , desipramine hydrochloride , methscopolamine bromide , and placebo was compared in a study with 40 severely enuretic boys . Both tricyclic antidepressants were superior to placebo and methscopolamine , but they did not differ from each other . Psychiatric disturbance , sleep measures , and other clinical parameters did not predict antienuretic response to tricyclics nor was there a psychotropic response . Plasma concentrations of imipramine and desipramine showed a significant correlation with clinical effect . However , true nonresponders were found , and tolerance to the antienuretic drugs developed in some boys reported by several investigators , Eiectroencephaiographic abnormalities were found in a large percent age of enuretic children by Michael and Sectznd.a , l~ and by others . Some investigators have report , , : frequent occurrences of i : ui , minor genito-urinary abnorma lit i , , ’ ... such as inflammation of the tri~~~ and verumontanum , changes in E;z~ , shape of the internal urethral open ing , and valves or stenosis of tl~~= urethra . Others have described high incidence of coronal adho sions , vulvitis or spina bifida ofcuh,% in enuretics.5 , n. 8 , 10,:Z : Z Still nth&dquo ; , , , have noted a relationship l ~ eti,‘c~~.·tz allergy 4 our epilepsy : Z1 and enun’si&dquo ; Despite these numerous reports . iii the overwhelming majority of c%ltt retic children none of these f : BB . iivi , Oxybutynin chloride ( Ditropan ) , a tertiary amine possessing anticholinergic and papaverine-like , direct muscular antispasmodic effects , has been used in controlled clinical studies in patients with neurovesical reflex activity , uninhibited bladders , enuresis , and primary muscle spasm . The cystometrically documented , synergistic , anticholinergic , and muscle relaxant activity of oxybutynin observed in these studies indicates that the drug can be highly effective in the management of reflex neurovesical dysfunction , enuresis , and bladder spasm Abstract The results of a long term follow-up of enuretics treated by conditioning techniques are presented . A high relapse rate has occurred after treatment with a combination of the “ bell and pad ” and stimulant drugs . The frequency of relapse is particularly high in the group of patients to whom Dexedrine had been administered . The importance of the relapse rate associated with conditioning treatment is discussed , and explanations and further research are considered |
12,495 | 30,098,161 | Conclusions and Relevance Current available evidence suggests that preoperative administration of tranexamic acid is safe and may reduce intraoperative bleeding as well as postoperative eyelid edema and ecchymosis in patients undergoing rhinoplasty | Importance Evidence has emerged on the efficacy of tranexamic acid to control blood loss and postoperative complications after rhinoplasty .
Objective To investigate the results of tranexamic acid use to reduce intraoperative bleeding , postoperative eyelid edema , and periorbital ecchymosis in rhinoplasty . | BACKGROUND The mode of administration for tranexamic acid ( TXA ) to significantly reduce the decrease in hemoglobin ( Hb ) , number of transfusions , relevant costs , and side effects in patients undergoing primary unilateral total knee arthroplasty ( TKA ) has not been resolved . METHODS A total of 560 patients undergoing primary unilateral TKA were r and omized into 4 groups : intravenous group ( 140 patients receiving 2 doses of 20 mg/kg intravenous TXA ) , topical group ( 140 patients administered 3.0 g topical TXA ) , oral group ( 140 patients given 2 doses of 20 mg/kg oral TXA ) , and a control group ( 140 patients not given TXA ) . The primary outcomes included postoperative 48-hour Hb loss and drainage volume , number of transfusions , transfusion and TXA costs , and thromboembolic complications . Secondary outcomes were postoperative inpatient time and wound healing 3 weeks after TKA . RESULTS Baseline data among the 4 groups were similar . The 48-hour Hb loss and drainage volume in the intravenous , topical , and oral groups were significantly less ( P < .05 ) than those in the control group , and the latter had significantly more transfusions and transfusion costs than the other 3 groups ( P < .05 ) . The TXA cost was lowest in the oral group compared with that in the topical and intravenous groups ( P < .05 ) . No differences in thromboembolic complications , postoperative inpatient time , or wound healing were observed among the groups . However , wound dehiscence and continuous wound discharge occurred in the topical group . CONCLUSION All the 3 modes of TXA administration significantly reduced postoperative Hb loss , the number of transfusions , and transfusion costs compared with those in the control group . No pulmonary embolism or infection was observed . Oral TXA is recommended because it provided a similar clinical benefit and result ed in the lowest TXA cost compared with the other 2 modes of TXA administration In our department we use an enhanced recovery protocol for joint replacement of the lower limb . This incorporates the use of intravenous tranexamic acid ( IVTA ; 15 mg/kg ) at the induction of anaesthesia . Recently there was a national shortage of IVTA for 18 weeks ; during this period all patients received an oral preparation of tranexamic acid ( OTA ; 25 mg/kg ) . This retrospective study compares the safety ( surgical and medical complications ) and efficacy ( reduction of transfusion requirements ) of OTA and IVTA . During the study period a total of 2698 patients received IVTA and 302 received OTA . After adjusting for a range of patient and surgical factors , the odds ratio ( OR ) of receiving a blood transfusion was significantly higher with IVTA than with OTA ( OR 0.48 ( 95 % confidence interval 0.26 to 0.89 ) , p = 0.019 ) , whereas the safety profile was similar , based on length of stay , rate of readmission , return to theatre , deep infection , stroke , gastrointestinal bleeding , myocardial infa rct ion , pneumonia , deep-vein thrombosis and pulmonary embolism . The financial benefit of OTA is £ 2.04 for a 70 kg patient ; this is amplified when the cost saving associated with significantly fewer blood transfusions is considered . Although the number of patients in the study is modest , this work supports the use of OTA , and we recommend that a r and omised trial be undertaken to compare the different methods of administering tranexamic acid Background Dexamethasone and tranexamic acid are used to decrease post-rhinoplasty periorbital edema and ecchymosis . We compared the impact of each medication separately or in combination in this regard . Methods A prospect i ve , r and omized triple-blinded study was undertaken on 60 patients who underwent primary open rhinoplasty . They were divided into four groups : Group D ( n = 15 ) received 8 mg dexamethasone , group T ( n = 15 ) received 10 mg/kg tranexamic acid , group DT ( n = 15 ) received both 8 mg dexamethasone and 10 mg/kg tranexamic acid , and group P ( n = 15 ) received neither medication and served as the placebo control group . The medications were given intravenously ( IV ) 1 h before and three doses every 8 h postoperatively . Digital photographs were taken on the first , third and seventh postoperative days . One expert examiner blinded to the study evaluated the periorbital edema and ecchymosis on a scale of 0–4 . Periorbital edema and ecchymosis were examined in all groups . Results In group D , group T and group DT , periorbital edema and ecchymosis ratings were significantly lower compared with the control group ( p < 0.01 ) . No statistically significant difference was seen in preventing or decreasing both periorbital edema and ecchymosis among group D , group T and group DT . Conclusion Tranexamic acid and dexamethasone , separately or in combination , had similar effects in reducing periorbital edema and ecchymosis in open rhinoplasty . Combined application did not show a significantly higher beneficial effect in this regard . Level of Evidence IIIThis journal requires that authors assign a level of evidence to each article . For a full description of these Evidence -Based Medicine ratings , please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 Background : One of the major problems in surgery is intraoperative bleeding which reduces visibility in the operative field . An important task for an anesthetist during head and neck surgery is to improve intraoperative visibility . Objectives : The purpose of this study was to compare the amount of bleeding using different doses of oral metoprolol during three common types of nasal operation ; rhinoplasty , septoplasty and functional endoscopic sinus surgery , as this is one of the complications during head and neck surgery . Patients and Methods : In a r and omized , controlled , open clinical trial , 88 patients who were c and i date s for nasal operations were studied . Patients entering the study were divided into four groups and r and omly assigned to receive 50 mg metoprolol a night before the operation , 50 mg metoprolol on the day of operation , 50 mg metoprolol on the night and on the day of operation , or a placebo . Following the patient ’s preparation on the operating table and after intubation , systolic and diastolic blood pressures were measured in a non-invasive oscillometric way , and their pulse rate was recorded simultaneously . All the data were recorded during the surgery as well . Bleeding was measured by the quality scale proposed by Formme and Boezaart . Results : There was a statistical significance between using metoprolol and the amount of intraoperative bleeding . All patients who received metoprolol the night before surgery and on the day of surgery had slight bleeding during the surgery . In addition , there was a statistical significance between patients ’ agitation levels and the time they received metoprolol . Conclusions : Decreases in both systolic blood pressure and heart rate to less than 60 beats per minute reduces intraoperative bleeding . These rates can be achieved by using beta-blocker drugs . In this study , using a double-dose of metoprolol significantly reduced intraoperative bleeding and improved the quality of the operative field . It also reduced patients ’ agitation in the recovery room Background : Perioperative bleeding is a common side effect of rhinoplasty which may impose the blood transfusion to the patients . As a result of risks and cost of blood transfusion , this study is planned to reduce blood loss in these surgeries . Since tranexamic acid ( TXA ) has been reported to reduce bleeding and subsequent possible need for blood transfusion , the purpose of this study was to evaluate the efficacy of oral TXA on blood loss during rhinoplasty . Methods and Material s : In this double-blind , r and omized , placebo-controlled clinical trial , 50 participants underwent rhinoplastic surgery . These participants were divided into 2 groups ; 25 were r and omly assigned to each 1 . The patients in the first group received 1 g ( 2 × 500 mg ) tranexamic acid tablets , and the patients in the second group received placebo 2 hours before starting the surgery . All patients were operated by the same surgical team and the same anesthetic techniques were used during the surgery . Gender , age , BMI , duration of operation , the amount of blood loss , and surgeon 's satisfaction rate were the variables studied . Results : The first group ( TXA group ) consisted of 11 males ( 44 % ) and 14 females ( 56 % ) and the second group consisted of 13 males ( 52 % ) and 12 females ( 48 % ) . There was no statistical difference in the distribution of the variables between the 2 groups , except for the blood loss , duration of operation , and surgeon 's satisfaction . The mean total blood loss was 144.6 ± 60.28 mL in “ group 1 ” and 199.6 ± 73.05 mL in “ group 2 ” ( P < 0.05 ) . Duration of operation in the first group was less than the second group ( 2.60 ± 0.53 hours vs. 2.99 ± 0.59 hours ) ( P = 0.017 ) . The surgeon was more satisfied with the quality of surgical field and visualization in “ group 1 ” ( 3.76 ± 0.72 ) than “ group 2 ” ( 2.16 ± 0.50 ) ( P = 0.001 ) . Conclusion : The preoperative administration of 1 g oral tranexamic acid significantly decreased the blood loss in patients undergoing rhinoplastic surgery without any significant adverse effects . Iranian registry no : I RCT 201312271674N10 ( www.i rct .ir ) Background There is a rich blood flow to the mucosa in the nasal region . In rhinoplasty , surgical procedures are performed in a narrow and confined space . So bleeding during surgery reduces visibility which can complicate the procedure . This study investigated the effects of the patient position on amount of intraoperative bleeding during surgical procedures . Patients and Methods This r and omized controlled trial was conducted on 71 patients who underwent elective rhinoplasty . The patients were operated on in three groups . Group 1 consisted of 23 patients who were operated on in the supine position ; Group 2 included 28 patients who were operated on using a 15 ° angle reverse Trendelenburg position ; Group 3 consisted of 20 patients who were operated on at a 20 ° angle reverse Trendelenburg position . Results There were statistically significant differences between the groups in regard to surgeon satisfaction and the amount of intraoperative bleeding . The amount of intraoperative bleeding in Group 1 was significantly higher than those of Groups 2 and 3 , and surgeon satisfaction was lower . Conclusions Reverse Trendelenburg position reduces intraoperative bleeding in rhinoplasty patients while facilitating the procedure compared to the supine position . Surgery at a 15 ° angle reverse Trendelenburg position provides the optimum working conditions by both significantly reducing intraoperative bleeding and allowing for comfortable conditions for the surgeon . Level of Evidence IThis journal requires that authors assign a level of evidence to each article . For a full description of these Evidence -Based Medicine ratings , please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 Background This r and omized , double-blind study was design ed to assess the effect of perioperative remifentanil with controlled hypotension on intraoperative bleeding , postoperative edema , and ecchymosis . Methods Fifty-two patients undergoing rhinoplasty were divided into 2 groups . The remifentanil group received 1 µg · kg−1 intravenously as a bolus before induction of anesthesia , 0.5 to 1 µg · kg−1 · h−1 by continuous intravenous infusion during the operation . After anesthesia induction with propofol ( 2–3 mg · kg−1 ) and fentanyl ( 1–15 µg · kg−1 ) , muscle relaxation was achieved with rocuronium ( 0.45–0.90 mg · kg−1 ) . Mean arterial pressure was maintained at 50 to 60 mm Hg in controlled hypotensive anesthesia achieved using remifentanil infusion . Perioperative hemodynamics and bleeding ; early postoperative pain and agitation scale ; postoperative first , third , and seventh day edema ; and ecchymosis were evaluated . Edema and ecchymosis were evaluated using grade d scale from 0 to 4 . Results Remifentanil reduced mean arterial pressure during the entire operative period and the first 30 minutes postoperatively ( P < 0.05 for these comparisons ) . Intraoperative bleeding also decreased ( P < 0.001 ) . There was a significant decrease in edema in both upper and lower eyelid edema on the first and third days in the remifentanil group , although this difference was not detected on the seventh day ( P1upper = 0.000 , P1lower = 0.000 , P3upper = 0.008 , and P3lower = 0.002 ) . Ecchymosis decreased significantly in both upper and lower eyelids on the first , third , and seventh days in the remifentanil group ( P1upper = 0.000 , P3upper = 0.000 , P3upper = 0.002 , P3lower = 0.002 , P7upper = 0.049 , and P7lower = 0.038 ) . There were no differences in postoperative pain and agitation between 2 groups . Conclusions Remifentanil with controlled hypotension may reduce edema and ecchymosis of the upper and lower eyelids , by reducing mean arterial pressure and amount of bleeding in rhinoplasty Introduction Extracorporeal circulation induces hemostatic alterations that lead to inflammatory response ( IR ) and postoperative bleeding . Tranexamic acid ( TA ) reduces fibrinolysis and blood loss after cardiopulmonary bypass ( CPB ) . However , its effects on IR and vasoplegic shock ( VS ) are not well known and elucidating these effects was the main objective of this study . Methods A case control study was carried out to determine factors associated with IR after CPB . Patients undergoing elective CPB surgery were r and omly assigned to receive 2 g of TA or placebo ( 0.9 % saline ) before and after intervention . We performed an intention-to-treat analysis , comparing the incidence of IR and VS . We also analyzed several biological parameters related to inflammation , coagulation , and fibrinolysis systems . We used SPSS version 12.2 for statistical purpose s. Results In the case control study , 165 patients were studied , 20.6 % fulfilled IR criteria , and the use of TA proved to be an independent protective variable ( odds ratio 0.38 , 95 % confidence interval 0.18 to 0.81 ; P < 0.01 ) . The clinical trial was interrupted . Fifty patients were r and omly assigned to receive TA ( 24 ) or placebo ( 26 ) . Incidence of IR was 17 % in the TA group versus 42 % in the placebo group ( P = 0.047 ) . In the TA group , we observed a significant reduction in the incidence of VS ( P = 0.003 ) , the use of norepinephrine ( P = 0.029 ) , and time on mechanical ventilation ( P = 0.018 ) . These patients showed significantly lower D-dimer , plasminogen activator inhibitor 1 , and creatine-kinase levels and a trend toward lower levels of soluble tumor necrosis factor receptor and interleukin-6 within the first 24 hours after CPB . Conclusion The use of TA attenuates the development of IR and VS after CPB.Trial registration numberIS RCT N05718824 Background : Tranexamic acid is an antifibrinolytic that has been shown to reduce blood loss and the need for transfusions when administered intravenously in total hip arthroplasty . Oral formulations of the drug are available at a fraction of the cost of the intravenous preparation . The purpose of this r and omized controlled trial was to determine if oral and intravenous formulations of tranexamic acid have equivalent blood-sparing properties . Methods : In this double-blinded trial , 89 patients undergoing primary total hip arthroplasty were r and omized to receive 1.95 g of tranexamic acid orally 2 hours preoperatively or a 1-g tranexamic acid intravenous bolus in the operating room prior to incision ; 6 patients were eventually excluded for protocol deviations , leaving 83 patients available for study . The primary outcome was the reduction of hemoglobin concentration . Power analysis determined that 28 patients were required in each group with a ±1.0 g/dL hemoglobin equivalence margin between groups with an alpha of 5 % and a power of 80 % . Equivalence analysis was performed with a two one-sided test ( TOST ) in which a p value of < 0.05 indicated equivalence between treatments . Results : Forty-three patients received intravenous tranexamic acid , and 40 patients received oral tranexamic acid . Patient demographic characteristics were similar between groups , suggesting successful r and omization . The mean reduction of hemoglobin was similar between oral and intravenous groups ( 3.67 g/dL compared with 3.53 g/dL ; p = 0.0008 , equivalence ) . Similarly , the mean total blood loss was equivalent between oral and intravenous administration ( 1,339 mL compared with 1,301 mL ; p = 0.034 , equivalence ) . Three patients ( 7.5 % ) in the oral group and one patient ( 2.3 % ) in the intravenous group were transfused , but the difference was not significant ( p = 0.35 ) . None of the patients in either group experienced a thromboembolic event . Conclusions : Oral tranexamic acid provides equivalent reductions in blood loss in the setting of primary total hip arthroplasty , at a greatly reduced cost , compared with the intravenous formulation . Level of Evidence : Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence INTRODUCTION The aim of this r and omized double-blind study was to evaluate the efficacy of Tranexamic acid ( TXA ) on intraoperative bleeding , postoperative eyelid edema , and postoperative periorbital ecchymosis in rhinoplasty . MATERIAL S AND METHODS Sixty rhinoplasty patients who needed hump reduction and lateral osteotomy were included and then r and omly assigned into two groups . In the intervention group ( n = 30 ) , 10 mg/kg of TXA was administered prior to the operation and in the control group , the patients were given 20 mL of normal saline . Intraoperative bleeding was evaluated by gravimetric method and pre and postoperative hemoglobin and hematocrit levels were determined . Eyelid edema and periorbital ecchymosis were evaluated using 0 - 4 points scoring system . Surgeon satisfaction was measured by asking questions of the surgeon . Data were analyzed by SPSS 20.0 ( P < 0.05 ) . RESULTS In total , 10 participants were excluded from the research , and 50 patients were included in the study . Mean ( SD ) of intraoperative bleeding was 213 ( 65 ) mL and 254 ( 55 ) mL in the intervention and control group , respectively , based on the clinical methods ( P = 0.013 ) . Level of hemoglobin was 266.69 in the control group versus 241.25 in the TXA group , indicating that this effect on the intraoperative bleeding was not significant ( P = 0.1 ) . Hematocrit differences before and after operation were significant ( P = 0.03 ) ( 247.06 mL in TXA vs. 279.2 mL in the control group ) . TXA had a statistically significant effect on the eyelid edema ( P = 0.03 ) , periorbital ecchymosis ( P = 0.04 ) , and surgeon satisfaction ( P = 0.03 ) . CONCLUSION Administration of 10 mm/kg TXA had a significant effect in decreasing the intraoperative bleeding rate , eyelid edema , and periorbital ecchymosis in the rhinoplasty with minimal side effects Background In cardiopulmonary bypass ( CPB ) patients , fibrinolysis may enhance postoperative inflammatory response . We aim ed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid ( TA ) reduced CPB-mediated inflammatory response ( IR ) . Methods We performed a r and omized , double-blind , dose-dependent , parallel-groups study of elective CPB patients receiving TA . Patients were r and omly assigned to either the single-dose group ( 40 mg/Kg TA before CPB and placebo after CPB ) or the double-dose group ( 40 mg/Kg TA before and after CPB ) . Results 160 patients were included , 80 in each group . The incident rate of IR was significantly lower in the double-dose-group TA2 ( 7.5 % vs. 18.8 % in the single-dose group TA1 ; P = 0.030 ) . After adjusting for hypertension , total protamine dose and temperature after CPB , TA2 showed a lower risk of IR compared with TA1 [ OR : 0.29 ( 95 % CI : 0.10 - 0.83 ) , ( P = 0.013 ) ] . Relative risk for IR was 2.5 for TA1 ( 95 % CI : 1.02 to 6.12 ) . The double-dose group had significantly lower chest tube bleeding at 24 hours [ 671 ( 95 % CI 549 - 793 vs. 826 ( 95 % CI 704 - 949 ) mL ; P = 0.01 corrected-P significant ] and lower D-dimer levels at 24 hours [ 489 ( 95 % CI 437 - 540 ) vs. 621(95 % CI : 563 - 679 ) ng/mL ; P = 0.01 corrected-P significant ] . TA2 required lower levels of norepinephrine at 24 h [ 0.06 ( 95 % CI : 0.03 - 0.09 ) vs. 0.20(95 CI : 0.05 - 0.35 ) after adjusting for dobutamine [ F = 6.6 ; P = 0.014 corrected-P significant].We found a significant direct relationship between IL-6 and temperature ( rho = 0.26 ; P < 0.01 ) , D-dimer ( rho = 0.24 ; P < 0.01 ) , norepinephrine ( rho = 0.33 ; P < 0.01 ) , troponin I ( rho = 0.37 ; P < 0.01 ) , Creatine-Kinase ( rho = 0.37 ; P < 0.01 ) , Creatine Kinase-MB ( rho = 0.33 ; P < 0.01 ) and lactic acid ( rho = 0.46 ; P < 0.01 ) at ICU arrival . Two patients ( 1.3 % ) had seizure , 3 patients ( 1.9 % ) had stroke , 14 ( 8.8 % ) had acute kidney failure , 7 ( 4.4 % ) needed dialysis , 3 ( 1.9 % ) suffered myocardial infa rct ion and 9 ( 5.6 % ) patients died . We found no significant differences between groups regarding these events . Conclusions Prolonged inhibition of fibrinolysis , using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding ( but not transfusion requirements ) in CPB patients . A question which remains unanswered is whether the dose used was ideal in terms of safety , but not in terms of effectiveness . Current Controlled Trials numberIS RCT N : IS RCT IMPORTANCE Postoperative edema and ecchymosis following rhinoplasty are a cause of anxiety for both patients and physicians and can affect the cosmetic results . Corticosteroids have been used to reduce these events . OBJECTIVE To determine whether preoperative use of dexamethasone sodium phosphate alters the occurrence of edema and ecchymosis following rhinoplasty . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled clinical trial at an institutional referral center among a sample of individuals with rhinomegaly . INTERVENTIONS Patients were r and omized into 2 groups . In group 1 , dexamethasone was intravenously injected before surgery . In group 2 , normal saline solution was intravenously injected before surgery . MAIN OUTCOMES AND MEASURES When patients returned at 1 week after surgery , st and ardized photographs were obtained . The photographs were analyzed by 5 plastic surgeons who were blinded as to whether dexamethasone or normal saline solution had been injected . The plastic surgeons rated the degree of edema and ecchymosis . RESULTS Forty-two patients participated in the study . R and omization by lottery result ed in 20 patients in group 1 and 22 patients in group 2 . Group 1 showed lower rates of postoperative ecchymosis than group 2 ; the difference of 0.62 ( P = .02 ) reflects less perceived ecchymosis when dexamethasone was administered . Group 1 also showed lower rates of postoperative edema than group 2 ; the difference of 0.68 ( P = .01 ) reflects less perceived edema when dexamethasone was administered . CONCLUSIONS AND RELEVANCE Preoperative use of dexamethasone reduced edema and ecchymosis at 7 days after rhinoplasty . Rigorous methods in this trial demonstrate the beneficial effect of preoperative corticosteroid administration in this surgical procedure . LEVEL OF EVIDENCE 1 PURPOSE The aim of this retrospective study was to evaluate the efficacy of dexamethasone with controlled hypotension on intraoperative bleeding and postoperative morbidity in rhinoplasty . MATERIAL S AND METHODS Sixty rhinoplasty patients required hump resection and lateral osteotomy were included in this study . The patients were r and omized into four groups . In group I ( n=15 ) , a single dose of 10mg/kg dexamethasone was intravenously administered at the beginning of the operation . In group II ( n=15 ) , the patients were given 2 doses of 10mg/kg intravenously dexamethasone at the beginning of the operation , and 24 hours after the operation . In group III ( n=15 ) , 3 doses of 10mg/kg intravenously dexamethasone were given at the beginning of the operation , before osteotomy and 24 hours after the operation . Group IV ( n=15 ) was assigned as control group and the patients were neither administered dexamethasone nor applied hypotension . All cases in groups I , II and III were operated under controlled hypotension . Systolic arterial pressure was aim ed to keep between 65 and 75 mmHg for controlled hypotensive anaesthesia . Controlled hypotension was achieved by a remifentanil infusion of 0.1 - 0.5 microg/kg/min , following a bolus of 1 microg/kg . Degree of eyelid oedema and periorbital soft-tissue ecchymosis was evaluated separately using a scale of 0 - 4 . Intraoperative blood loss was recorded for each patient . Patients were evaluated at 24 hours and postoperative days 2 , 5 , 7 , and 10 . RESULTS In groups I , II and III , intraoperative bleeding was more decreased and the operation time was significantly shorter compared with control group ( P<0.001 ) . Eyelid oedema and periorbital ecchymosis were significantly decreased in groups I , II and III at the following postoperative 7 and 10 days ( P<0.001 ) . There was statistically significant difference between group III and other groups at the postoperative 5 and 7 days in lower eyelid oedema ( P<0.001 ) , upper and lower eyelid ecchymosis ( P<0.001 and 0.004 , respectively ) . There were no postoperative complications with using steroid in any of the groups . CONCLUSION Three doses of dexamethasone with controlled hypotension considerably reduced postoperative morbidities of rhinoplasty with osteotomy as well as intraoperative bleeding . Thus , in group III receiving 3 doses of steroid , when compared to other groups , more uneventful postoperative period were provided for surgeon and the patients Objective : To identify independent predictors of 30-day venous thromboembolism ( VTE ) events requiring treatment after outpatient surgery . Background : An increasing proportion of surgical procedures are performed in the outpatient setting . The incidence of VTE requiring treatment after outpatient surgery is unknown . Methods : Prospect i ve observational cohort study using the American College of Surgeons National Surgical Quality Improvement Program ( ACS-NSQIP ) data base from 2005 to 2009 . Adult patients who had outpatient surgery or surgery with subsequent 23-hour observation were included . The main outcome measure was 30-day VTE requiring treatment . Patients were r and omly assigned to derivation ( N = 173,501 ) or validation ( N = 85,730 ) cohorts . Logistic regression examined independent risk factors for 30-day VTE . A weighted risk index was created and applied to the validation cohort . Stratified analyses examined 30-day VTE by risk level . Results : Thirty-day incidence of VTE for the overall cohort was 0.15 % . Independent risk factors included current pregnancy ( adjusted odds ratio [ OR ] = 7.80 , P = 0.044 ) , active cancer ( OR = 3.66 , P = 0.005 ) , age 41 to 59 years ( OR = 1.72 , P = 0.008 ) , age 60 years or more ( OR = 2.48 , P < 0.001 ) , body mass index 40 kg/m2 or higher ( OR = 1.81 , P = 0.015 ) , operative time 120 minutes or more ( OR = 1.69 , P = 0.027 ) , arthroscopic surgery ( OR = 5.16 , P < 0.001 ) , saphenofemoral junction surgery ( OR = 13.20 , P < 0.001 ) , and venous surgery not involving the great saphenous vein ( OR = 15.61 , P < 0.001 ) . The weighted risk index identified a 20-fold variation in 30-day VTE between low ( 0.06 % ) and highest risk ( 1.18 % ) patients . Conclusions : Thirty-day VTE risk after outpatient surgery can be quantified using a weighted risk index . The risk index identifies a high-risk subgroup of patients with 30-day VTE rates of 1.18 % BACKGROUND Steroids have proven to be of some benefit in rhinoplasty edema and ecchymosis when administered at a high and repeated dose . OBJECTIVE To evaluate the effects of single-dose , long-acting intramuscular steroids on postoperative edema and ecchymosis after closed rhinoplasty with osteotomies compared with placebo . METHODS A r and omized , double-blinded , placebo-controlled trial was performed . Fifty-four patients were r and omly assigned to two groups : 28 received a single dose of long-acting dexamethasone ( mean [ ± SD ] dose 16±4 mg ) immediately before anesthetic induction ; the remaining 26 received an intramuscular injection of saline solution . The same surgeon performed all surgeries , with patients under general anesthesia . Acetaminophen was the only analgesic used to control postoperative pain . High-resolution digital photographs were taken on postoperative days 1 , 3 , 7 and 14 . Scoring was performed separately for eyelid swelling and ecchymosis by an independent observer using a grade d scale ( 0 to 5 ) for edema and a scoring system ( 0 to 13 ) for ecchymosis . RESULTS No statistically significant differences in terms of age , sex or amount of bleeding during surgery were found between the two groups . No statistically significant difference was observed in the decrease of both ecchymosis and edema between placebo and high-dose , long-acting dexamethasone . A statistically significant difference in operation time was found , favouring the steroid group . No severe complications were observed due to steroid use . DISCUSSION Osteotomies are basically a form of ( controlled ) trauma , with considerable disruption of the abundant blood vessels in this facial region and , therefore , are associated with with undesirable effects . A recent meta- analysis failed to show benefits of the use of steroids after postoperative day 3 . Only a trend toward reduction in edema and ecchymosis with the use of long-acting steroids compared with placebo was demonstrated in the present study . CONCLUSION There was no benefit in administering single-dose , long-acting steroids in patients undergoing closed rhinoplasty with osteotomies Many facial plastic surgeons use perioperative steroids to reduce postoperative edema and morbidity . This use of steroids is based more on theory and anecdotal experience than on controlled studies . We studied 49 patients undergoing rhinoplasty in a r and omized , double-blind fashion to evaluate the effects of perioperative and postoperative steroid use . We found significantly less postoperative eyelid and paranasal edema in those patients receiving steroids . In addition , trends toward less ecchymosis , less intranasal edema , and less discomfort in the patients receiving steroids were noted BACKGROUND Although some studies about the effects of steroids on surgical trauma in closed or combined ( closed and open together ) rhinoplasty have been reported in the literature , still more information is needed in order to enlighten rhinoplasty surgeons . The purpose of this study is to evaluate the anti-inflammatory activity of steroids administered in high doses to prevent and decrease periorbital ecchymosis and oedema in patients who underwent open rhinoplasty with osteotomies by the same surgeon . This is the first study in open rhinoplasty alone . METHODS The study was performed on 40 patients , under general anaesthesia . Patients were divided r and omly into five groups ( eight patients in each group ) ; the groups comprised : a single 250 mg dose of methylprednisolone ( Group I ) , a single 500 mg dose of methylprednisolone ( Group II ) , four 250 mg doses of methylprednisolone ( Group III ) , four 500 mg doses of methylprednisolone ( Group IV ) and placebo ( Group V ) . Digital photographs were taken of each patient on the first , third and seventh postoperative days . Scorings of eyelid swelling and ecchymosis were evaluated separately using a grade d scale from 0 to ( + ) 4 by three observers , independently . Additionally , blood sample s were taken for the evaluations of C-reactive protein ( CRP ) , white blood cell ( WBC ) and erythrocyte sedimentation rate ( ESR ) on the same days . RESULTS Clinical ly and statistically significant difference was observed in the decrease of both ecchymosis and oedema , between the placebo and high dose methylprednisolone groups , which is effective to prevent and to decrease both the ecchymosis and oedema in open rhinoplasty with osteotomies . CRP was the most sensitive acute phase reactant among CRP , ESR and WBC . No complication was observed due to steroid usage . CONCLUSIONS We can confidently say that high dose methylprednisolone is effective in preventing and reducing both the periorbital ecchymosis and oedema in open rhinoplasty with osteotomies and it can be used safely for this purpose Aims The aim of this study was to examine the efficacy and safety of multiple boluses of intravenous ( IV ) tranexamic acid ( TXA ) on the hidden blood loss ( HBL ) and inflammatory response following primary total hip arthroplasty ( THA ) . Patients and Methods A total of 150 patients were allocated r and omly to receive a single bolus of 20 mg/kg IV TXA before the incision ( group A ) , a single bolus followed by a second bolus of 1 g IV‐TXA three hours later ( group B ) or a single bolus followed by two boluses of 1 g IV‐TXA three and six hours later ( group C ) . All patients were treated using a st and ard peri‐operative enhanced recovery protocol . Primary outcomes were HBL and the level of haemoglobin ( Hb ) as well as the levels of C‐reactive protein ( CRP ) and interleukin‐6 ( IL‐6 ) as markers of inflammation . Secondary outcomes included the length of stay in hospital and the incidence of venous thromboembolism ( VTE ) . Results The mean HBL was significantly lower in group C ( 402.13 ml st and ard deviation ( sd ) 225.97 ) than group A ( 679.28 ml sd 277.16 , p < 0.001 ) or B ( 560.62 ml sd 295.22 , p = 0.010 ) . The decrease in the level of Hb between the pre‐operative baseline and the level on the third post‐operative day was 30.82 g/L ( sd 6.31 g/L ) in group A , 27.16 g/L ( sd 6.83 ) in group B and 21.98 g/L ( sd 3.72 ) in group C. This decrease differed significantly among the three groups ( p < 0.01 ) . The mean level of CRP was significantly lower in group C than in the other two groups on the second ( p ≤ 0.034 ) and third post‐operative days ( p ≤ 0.014 ) . The levels of IL‐6 were significantly lower in group C than group A on the first three post‐operative days ( p = 0.023 ) . The mean length of stay was significantly lower in group C than group A ( p = 0.023 ) . No VTE or other adverse events occurred . Conclusion Multiple boluses of IV‐TXA can effectively reduce HBL following primary THA . A regime of three boluses leads to a smaller decrease in the level of Hb , less post‐operative inflammation and a shorter length of stay in hospital than a single bolus Nasal osteotomies are the most important cause of periorbital edema and ecchymosis . Injection of lidocaine and adrenaline is recommended to reduce bleeding . Whilst the lidocaine and adrenaline combination ( LAC ) is cl aim ed to reduce postoperative ecchymosis and edema , this effect remains to be proven conclusively . This study , on 48 patients , was design ed to investigate the effects of LAC injection on postoperative edema/ecchymosis in rhinoplasty . LAC was applied at a r and om side prior to the lateral osteotomy . The opposite side was used as a control . The relationship between edema/ecchymosis and the degree of LAC on the injected and uninjected sides was evaluated on the first , third and seventh day postoperatively . The relationships between edema and ecchymosis with operation time and intraoperative systolic blood pressure were also evaluated . Bleeding was reduced on the side treated with LAC ( p=0.050 ) . The degrees of edema/ecchymosis increased with increases in the duration of operation and the systolic blood pressure on the first postoperative day for the LAC-applied side ( p<0.05 ) . This correlation was not observed on the opposite side ( p>0.05 ) . Application of LAC reduces bleeding during rhinoplasty and pain control postoperatively but reduced edema and ecchymosis should not be expected following LAC application |
12,496 | 27,275,813 | In the anterior vaginal compartment , synthetic nonabsorbable mesh consistently showed improved anatomic and bulge symptom outcomes compared with native tissue repairs based on meta-analyses .
Other subjective outcomes , including urinary incontinence or dyspareunia , generally did not differ .
Biologic graft or synthetic absorbable mesh use did not provide an advantage in any compartment .
Synthetic mesh use in the posterior or apical compartments did not improve success .
: Synthetic mesh augmentation of anterior wall prolapse repair improves anatomic outcomes and bulge symptoms compared with native tissue repair .
Biologic grafts do not improve prolapse repair outcomes in any compartment .
Mesh erosion occurred in up to 36 % of patients , but reoperation rates were low | OBJECTIVE : To up date clinical practice guidelines on graft and mesh use in transvaginal pelvic organ prolapse repair based on systematic review . | OBJECTIVE This study was undertaken to compare outcomes after anterior colporrhaphy with and without a solvent dehydrated cadaveric fascia lata graft . STUDY DESIGN A total of 162 women were enrolled in a prospect i ve , r and omized trial that evaluated the impact of a solvent dehydrated cadaveric fascia lata patch on recurrent anterior vaginal prolapse . Subjects were r and omly assigned to st and ard colporrhaphy with or without a patch . Before and after surgery , subjects were evaluated by both the Baden-Walker and pelvic organ prolapse quantification systems . " Failure " was defined as stage II anterior wall prolapse or worse . RESULTS Of 154 women r and omly assigned ( 76 patch : 78 no patch ) , all underwent surgery and 153 ( 99 % ) returned for follow-up . Sixteen women ( 21 % ) in the patch group and 23 ( 29 % ) in the control group experienced recurrent anterior vaginal wall prolapse ( P = .229 ) . Only 26 % of all recurrences were symptomatic . Concomitant transvaginal Cooper 's ligament sling procedures were associated with a dramatic decrease in recurrent prolapse ( odds ratio [ OR ] 0.105 , P < .0001 ) . CONCLUSION Solvent dehydrated fascia lata as a barrier does not decrease recurrent prolapse after anterior colporrhaphy . Transvaginal bladder neck slings were associated with a significant reduction in the risk of recurrent anterior wall prolapse OBJECTIVE : To present the 3-year outcomes of a double-blind , multicenter , r and omized trial comparing vaginal prolapse repair with and without mesh . METHODS : This was a planned final analysis of women with Pelvic Organ Prolapse Quantification ( POP-Q ) stage 2–4 prolapse r and omized to traditional vaginal prolapse surgery without mesh and vaginal colpopexy repair with mesh . We evaluated anatomic , symptomatic , and combined cure rates for those with at least 3-year vali date d quality -of-life question naires and 2- or 3-year postoperative blinded POP-Q examination . Participants undergoing reoperation for recurrent prolapse were removed for anatomic and subjective outcomes analysis and considered failures for combined outcomes analysis . RESULTS : Sixty-five women were enrolled ( 33 mesh , 32 no mesh ) before the study was prematurely halted as a result of a 15.6 % mesh exposure rate . At 3 years , 51 of 65 ( 78 % ) had quality -of-life question naires ( 25 mesh , 26 no mesh ) and 41 ( 63 % ) had examinations . Three participants died , three required reoperation for recurrent prolapse ( all in mesh group ) , and eight were lost to follow-up . No differences were observed between groups at 3 years for prolapse stage or individual prolapse points . Stage improved for each group ( 90 % and 86 % ) from baseline to 3 years ( P<.01 ) . Symptomatic improvement was observed with no differences in scores between groups . Cure rates did not differ between groups using a variety of definitions , and anatomic cure was lowest for the anterior compartment . CONCLUSION : There was no difference in 3-year cure rates when comparing patients undergoing traditional vaginal prolapse surgery without mesh with those undergoing vaginal colpopexy repair with mesh . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00475540 . LEVEL OF EVIDENCE : OBJECTIVE : To compare anatomical and patient-reported outcomes at 12 months postoperatively for women who had anterior compartment pelvic organ prolapse ( POP ) surgery using a repair augmented with porcine small intestine submucosa mesh ( Mesh Group ) compared with those who had a native tissue repair ( No Mesh Group ) . METHODS : This was a r and omized controlled trial with 12 months follow-up . The surgical procedure was identical in both groups except for the placement of intervening mesh . The primary outcome was anatomical “ cure ” ( Ba of −1 or less on Pelvic Organ Prolapse Quantification [ POP-Q ] ) . Secondary outcomes included POP-Q stage , patient-reported outcomes , and patient satisfaction . The study was powered to detect a 40 % difference at 80 % power ( & agr;=0.05 ) . RESULTS : Fifty-seven women were r and omized ( 28 to Mesh Group , 29 to No Mesh Group ) . Forty-five ( 79 % ) underwent concomitant surgery . At the 12-month follow-up , 56 % ( 15/27 ) in the Mesh Group and 61 % ( 17/28 ) in the No Mesh Group were considered cured ( relative risk 0.90 , 95 % confidence interval 0.52–1.54 ) . There were no significant differences between groups in recurrent or persistent prolapse ( 7 % in each group ) nor in patient-reported outcomes at 12 months . Pelvic girdle pain occurred in 4 of 27 in the Mesh Group and 3 of 28 in the No Mesh Group . CONCLUSION : No significant differences were observed in anatomical or patient-reported outcomes outcome parameters at 12 months after correction of symptomatic anterior POP by mesh or no mesh repair . In our study , porcine small intestine submucosa mesh did not confer additional benefit over a native tissue repair . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT0095544 . LEVEL OF EVEDIENCE : Introduction and hypothesisTo compare the efficacy of a collagen-coated polypropylene mesh and anterior colporrhaphy in the treatment of stage 2 or more anterior vaginal wall prolapse . Methods Prospect i ve , r and omized , multicenter study conducted between April 2005 and December 2009 . The principal endpoint was the recurrence rate of stage 2 or more anterior vaginal wall prolapse 12 months after surgery . Secondary endpoints consisted of functional results and mesh-related morbidity . Results One hundred and forty-seven patients were included , r and omized and analyzed : 72 in the anterior colporrhaphy group and 75 in the mesh group . The anatomical success rate was significantly higher in the mesh group ( 89 % ) than in the colporrhaphy group ( 64 % ) ( p = 0.0006 ) . Anatomical and functional recurrence was also less frequent in the mesh group ( 31.3 % vs 52.2 % , p = 0.007 ) . Two patients ( 2.8 % ) were reoperated on in the colporrhaphy group for anterior vaginal wall prolapse recurrence . No significant difference was noted regarding minor complications . An erosion rate of 9.5 % was noted . De novo dyspareunia occurred in 1/14 patients in the colporrhaphy group and in 3/13 patients in the mesh group . An analysis of the quality of life question naires showed an overall improvement in both groups , with no statistical difference between them . Satisfaction rates were high in both groups ( 92 % in the colporrhaphy group and 96 % in the mesh group ) . Conclusion Trans-obturator Ugytex ® mesh used to treat anterior vaginal wall prolapse gives better 1-year anatomical results than traditional anterior colporrhaphy , but with small a increase in morbidity in the mesh group The aim of this study was to evaluate the anatomical and functional results of a low-weight polypropylene mesh coated with an absorbable film in prolapse surgery by vaginal route . We have conducted a prospect i ve multicentre study in 13 gynaecological and urological units . There were 230 patients requiring repair for anterior or posterior vaginal prolapse included . The present report is based on the analysis of the first 143 patients evaluated after at least 10 months follow-up . All patients were operated by the vaginal route using a specially design ed mesh ( Ugytex , Sofradim , France ) . Prolapse severity were evaluated using the Pelvic Organ Prolapse staging system . Symptoms and quality of life were evaluated preoperatively and during follow-up using the vali date d Pelvic Floor Distress Inventory ( PFDI ) and Pelvic Floor Impact Question naire ( PFIQ ) self- question naires . Mean age was 63 years ( 37–91 ) . Anterior , posterior and anterior – posterior repair with the mesh were performed in 67 ( 46.9 % ) , 11 ( 7.7 % ) and 65 ( 45.4 % ) patients , respectively . With a mean follow-up of 13 months ( 10–19 ) , 132 patients were considered anatomically cured ( 92.3 % ) with a recurrence rate of 9 of 132 for cystocele ( 6.8 % ) and 2 of 76 for rectocele ( 2.6 % ) . Nine vaginal erosions occurred ( 6.3 % ) , six of them necessitated another procedure by simple excision . The rate of de novo dyspareunia was 12.8 % . At follow-up , improvement of PFDI and PFIQ scores were highly significant ( p<0.0001 ) . The use of low-weight polypropylene mesh coated with a hydrophilic absorbable film for vaginal repair of genital prolapse seems to decrease local morbidity while maintaining low recurrence rates Introduction and hypothesisThis trial aim ed to compare the outcomes of native vaginal tissue repair versus polypropylene mesh repair for the treatment of severe genital prolapse . Methods This multicenter r and omized trial included 184 women , with POP-Q stage 3 or 4 . They were r and omly assigned to undergo surgical treatment using native tissue repair ( n = 90 ) or synthetic mesh repair ( n = 94 ) . Native tissue repair surgery was performed according to site-specific defects , including sacrospinous ligament fixation for apical defects . Mesh repair ( Prolift ™ ) was performed in accordance with manufacturer recommendations . Hysterectomy was performed in all cases of uterine prolapse . Statistical tests were used to compare between-group and within-group differences before the surgery and at 1-year follow-up . We considered cure to have occurred when the POP-Q point evaluation was equal to or less than 0 and POP-Q point C better than or equal to half the total vaginal length ( TVL ) after 1 year . The patients answered the Prolapse Quality -of-Life Question naire ( PQoL ) and the Sexual Quotient Female Version ( QS-F ) question naire . Results Both groups were homogeneous preoperatively . There were no differences between the groups in operative time , complications or pain . At 1-year follow-up , anatomical cure rates were better in the mesh group in the anterior compartment ( p = 0.019 ) . Significant improvement in PQoL scores at 1-year follow up were observed in each group ; between-group comparisons of changes in PQoL scores revealed greater improvement in the mesh group . Conclusion Both techniques were effective . Anatomical efficacy was superior in the mesh group regarding the anterior compartment ; quality of life changes were also greater in the mesh group . Complications were significantly higher in the mesh group Introduction and hypothesisThe aim of the study was to compare the efficacy and safety of transvaginal trocar-guided polypropylene mesh insertion with traditional colporrhaphy for treatment of anterior vaginal wall prolapse . Methods This is a r and omized controlled trial in which women with advanced anterior vaginal wall prolapse , at least stage II with Ba ≥ + 1 cm according to the Pelvic Organ Prolapse Quantification ( POP-Q ) classification , were r and omly assigned to have either anterior colporrhaphy ( n = 39 ) or repair using trocar-guided transvaginal mesh ( n = 40 ) . The primary outcome was objective cure rate of the anterior compartment ( point Ba ) assessed at the 12-month follow-up visit , with stages 0 and I defined as anatomical success . Secondary outcomes included quantification of other vaginal compartments ( POP-Q points ) , comparison of quality of life by the prolapse quality of life ( P-QOL ) question naire , and complication rate between the groups after 1 year . Study power was fixed as 80 % with 5 % cutoff point ( p < 0.05 ) for statistical significance . Results The groups were similar regarding demographic and clinical preoperative parameters . Anatomical success rates for colporrhaphy and repair with mesh placement groups were 56.4 vs 82.5 % ( 95 % confidence interval 0.068–0.54 ) , respectively , and the difference between the groups was statistically significant ( p = 0.018 ) . Similar total complication rates were observed in both groups , with tape exposure observed in 5 % of the patients . There was a significant improvement in all P-QOL domains as a result of both procedures ( p < 0.001 ) , but they were not distinct between groups ( p > 0.05 ) . Conclusions Trocar-guided transvaginal synthetic mesh for advanced anterior POP repair is associated with a higher anatomical success rate for the anterior compartment compared with traditional colporrhaphy . Quality of life equally improved after both techniques . However , the trial failed to detect differences in P-QOL scores and complication rates between the groups Introduction and hypothesisVaginal mesh kits are increasingly used in the management of pelvic organ prolapse . This study aim ed to determine similarity of outcomes of the Anterior Prolift ® with Perigee ® systems for anterior compartment prolapse . Methods Consecutive women undergoing Perigee ® or Anterior Prolift ® for symptomatic stage 2 or greater anterior vaginal prolapse were prospect ively evaluated . Main outcome measures included objective and subjective success rates , perioperative outcomes , patient satisfaction , and complications . Results One hundred and six women ( Prolift , 52 ; Perigee , 54 ) completed question naires , and 91 ( Prolift , 46 ; Perigee , 45 ) were examined postoperatively . At follow-up ( Prolift : median , 11.0 ; range , 5–23 months ; Perigee : median , 11.5 ; range , 6–23 months ) , objective success rates ( Prolift , 89 % ; Perigee , 80 % ; p = 0.23 ) , subjective success rates ( Prolift , 94 % ; Perigee , 96 % ; p = 0.62 ) , mean ± SD patient satisfaction ( Prolift , 8.2 ± 2.0 ; Perigee , 8.2 ± 1.8 ; p = 0.91 ) , and complication rates did not differ significantly between the two groups . Conclusions The Anterior Prolift ® was found to not differ significantly from Perigee ® at 11 months OBJECTIVE To compare the use of polypropylene mesh ( PM ) and the traditional anterior vaginal wall colporraphy in women with anterior vaginal wall prolapse ( AVWP ) using objective and subjective tests and evaluation of quality of life ( QoL ) . MATERIAL S AND METHODS One hundred women were r and omly distributed in two preoperatory groups . The first group ( mesh ) ( n = 45 ) received a PM implant and the control group ( n = 55 ) was su bmi tted to traditional colporraphy . Postoperatory follow-up was done after 12 months . The primary objective was the correction of the Ba point ≤ -2 POP-Q ( Pelvic Organ Prolapse Quantification System ) and the secondary objective was the improvement of vaginal symptoms and QoL through ICIQ-VS ( International Consultation on Incontinence Question naire - Vaginal Symptoms ) . Complications related to the use of PM or not were also described . RESULTS There was a significant difference between all POP-Q measures of pre- and postoperatory periods of each group in particular . There was a significant difference of the Ba point of the postoperatory period between the Mesh and Control group . The mean of Ba point in the Mesh group was statistically lower than of the Control group , depicting the better anatomical result of the first group . Both techniques improved vaginal symptoms and QoL. The most frequent complication of the Mesh group was prepubic hematoma in the perioperative period . In 9.3 % of the cases treated with mesh it was observed PM exposition at the anterior vaginal wall after 12 months , being most of them treated clinical ly . CONCLUSION The treatment of AVWP significantly improved the Ba point in the Mesh group in comparison to the Control group . There were no differences of the vaginal symptoms and QoL between the two groups after 12 months . There were few and low grade complications on both groups The aim of this study was to compare the efficiency of polypropylene mesh surgery with the site-specific repair surgeries in the treatment of cystocoeles . We r and omized 90 patients into two groups according to a computer-based program . After a 12-month ( mean ) follow up , we noticed that the polypropylene mesh surgery yielded good anatomical results . Acceptable anatomical cure rates were 91 and 72 % in the mesh surgery group and site-specific surgery group , respectively . There were three cases ( 6.9 % ) of mesh erosion . One case of urinary retention and two cases of de novo dyspareunia were seen in the mesh surgery group . De novo stress urinary incontinence developed in three patients in the site-specific surgery group . We concluded that surgery with light polypropylene mesh ( Sofradim ® , Parietene ) is superior to the site-specific surgery in the treatment of cystocoeles We compared safety and efficacy of Gynemesh PS ® and Pelvicol ® for recurrent cystocele repair . One hundred ninety patients were r and omly divided into Gynemesh PS ® and Pelvicol ® groups and underwent tension-free cystocele repair . The Chi-square test was used to compare categorical variables , the paired t test for continuous parametric variables , and the Mann – Whitney test for continuous nonparametric variables . Ninety-six Gynemesh PS ® patients and 94 Pelvicol ® patients were studied . Mesh erosions occurred in 6.3 % of Gynemesh PS ® patients . No erosions were observed in Pelvicol ® patients ( p = 0.02 ) . Objective cure was 71.9 % for Gynemesh PS ® and 56.4 % for Pelvicol ® ( p = 0.06 ) . Subjective cure was the same in both groups except for better sexuality in the Pelvicol ® group . At 24 months follow-up , only Gynemesh PS ® patients had mesh erosions . Anatomical outcome was similar in the two groups . Pelvicol ® gave a better impact on voiding and sexuality OBJECTIVE : To present 3-month outcomes of a double-blind , multicenter r and omized controlled trial comparing traditional vaginal prolapse surgery without mesh with vaginal surgery with mesh . METHODS : Women with pelvic organ prolapse quantification prolapse stages 2–4 were r and omized to vaginal colpopexy repair with mesh or traditional vaginal colpopexy without mesh . The primary outcome measure was objective treatment success ( pelvic organ prolapse quantification stage 1 or lower ) at 3 months . Secondary outcome measures included quality -of-life variables and complication rates . RESULTS : Sixty-five women were recruited from January 2007 to August 2009 , when the study was halted due to predetermined stopping criteria for vaginal mesh erosion at a median follow-up of 9.7 months ( range , 2.4–26.7 months ) . Thirty-two women underwent mesh colpopexy ( 24 anterior mesh , eight total mesh ) , and 33 women had vaginal colpopexies without mesh ( primarily uterosacral ligament suspension ) and concurrent colporrhaphy . There were no statistically significant baseline differences between the mesh and no-mesh groups with respect to demographics , menopausal status , and race . Analysis of the mesh and no-mesh women found no difference with respect to overall recurrence ( mesh : 19 [ 59.4 % ] compared with no mesh : 24 [ 70.4 % ] , P=.28 ) . There were five ( 15.6 % ) vaginal mesh erosions . Two cystotomies and one blood transfusion occurred in the mesh group only . Subjective cure of bulge symptoms was noted in 93.3 % of mesh patients and 100 % of no-mesh patients . Furthermore , subjective quality -of-life measurements did not differ between the two groups at baseline or 3 months postoperatively . CONCLUSION : At 3 months , there is a high vaginal mesh erosion rate ( 15.6 % ) with no difference in overall objective and subjective cure rates . This study questions the value of additive synthetic polypropylene mesh for vaginal prolapse repairs . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00475540 . LEVEL OF EVIDENCE : INTRODUCTION Surgical treatment of pelvic organ prolapse ( POP ) affects sexual function . Generally , this results in improved sexual function , but deterioration is reported also . AIM The purpose of this study was to evaluate and compare sexual function in patients with recurrent POP undergoing either a vaginal surgical repair with native tissue or a trocar-guided mesh insertion . METHODS Sexually active patients r and omly assigned to either native tissue repair or trocar-guided mesh insertion , which had completed the pelvic organ prolapse (POP)/urinary incontinence sexual question naire ( PISQ-12 ) both at baseline and at 12 months , were included . Total , subscale , and individual question analysis were performed . Logistic regression was used to identify factors that were independently associated with improvement/deterioration in total PISQ-12 scores . MAIN OUTCOME MEASURES Primary outcome was sexual function at 12 months following surgery , measured by the short form of the pelvic organ prolapse/urinary incontinence sexual question naire ( PISQ-12 ) . Secondary outcomes were the identification of factors independently associated with change in PISQ-12 scores and changes in individual PISQ-12 question scores . RESULTS Sixty patients were included ; 32 in the mesh arm and 28 in the native tissue arm . At 12 months , PISQ-12 scores were not different in both treatment arms ( 34.3 , st and ard deviation [ SD ] 6.7 vs. 34.7 , SD 5.7 ) , but improvement was detected in the native tissue arm , whereas PISQ-12 total score remained unchanged in the mesh arm . Deteriorations were observed in the behavioral/emotive subscale and partner-related items in the mesh arm . In the native tissue arm , significant improvements in the physical and partner-related subscales were observed . The presence of mesh exposure was independently associated with deterioration in total PISQ-12 score . CONCLUSION At 12 months , PISQ-12 scores were not different in either treatment arm , but were affected differently by trocar-guided mesh insertion or by native tissue repair . Mesh exposure was independently associated with deterioration in sexual function Introduction and hypothesisThe effect of a Pelvicol ® graft compared with a conventional anterior vaginal repair was evaluated in this r and omised controlled study . Methods Only patients with a stage II or higher ( Ba ≥ −1 ) defect were included . Results Thirty-one patients were allocated to a conventional anterior repair ; 30 to Pelvicol ® graft . At 12 months follow-up , four patients among controls ( 15 % ) and two in the graft group ( 7 % ) had objective recurrence . Among controls , the difference at 3 months follow-up in Ba was 6.0 cm when compared with the position of Ba prior to surgery . In the graft group , the difference was 7.0 cm ( P < 0.05 ) . This difference was still present at 12 months follow-up ( 6.0 vs. 7.0 cm ; P < 0.05 ) . Conclusions The implantation of a Pelvicol ® graft does not improve the POP-Q stage Introduction and hypothesisThe objective of this study was to compare the anatomical and quality of life outcomes of a posterior polypropylene mesh kit versus sacrospinous ligament fixation at the time of hysterectomy for the treatment of uterine prolapse . Methods Thirty-two women aged 50 to 75 years with stage III or IV ( pelvic organ prolapse quantification system/International Continence Society ) uterine prolapse were r and omized into two groups ( group 1 : polypropylene mesh , Nazca R ® , Promedon , Cordoba , Argentina ; group 2 : sacrospinous ligament fixation ) . Results At 12-month follow-ups , we observed the same anatomical results in both groups . The median operating time , intraoperative blood loss , and perioperative complications were also equal in both groups . There were five cases ( 35.71 % ) of mesh erosion , and prolapse of the anterior vaginal wall ( cystocele ) occurred in 50 % of the patients . Conclusions Similar anatomical and quality of life outcomes were observed with polypropylene mesh and sacrospinous ligament fixation for the treatment of uterine prolapse . Complication rate was higher in the mesh group OBJECTIVE : The aim of this study was to compare female sexual function after surgical treatment of anterior vaginal prolapse with either small intestine submucosa grafting or traditional colporrhaphy . METHODS : Subjects were r and omly assigned , preoperatively , to the small intestine submucosa graft ( n = 29 ) or traditional colporrhaphy ( n = 27 ) treatment group . Postoperative outcomes were analyzed at 12 months . The Female Sexual Function Index question naire was used to assess sexual function . Data were compared with independent sample s or a paired Student 's t-test . Clinical Trials.gov : NCT00827528 . RESULTS : In the small intestine submucosa group , the total mean Female Sexual Function Index score increased from 15.5±7.2 to 24.4±7.5 ( p<0.001 ) . In the traditional colporrhaphy group , the total mean Female Sexual Function Index score increased from 15.3±6.8 to 24.2±7.0 ( p<0.001 ) . Improvements were noted in the domains of desire , arousal , lubrication , orgasm , satisfaction , and pain . There were no differences between the two groups at the 12-month follow-up . CONCLUSIONS : Small intestine submucosa repair and traditional colporrhaphy both improved sexual function postoperatively . However , no differences were observed between the two techniques OBJECTIVE : To compare anterior colporrhaphy with and without a tailored mesh . METHODS : Postmenopausal women with anterior vaginal prolapse to the hymen or beyond were r and omly assigned to undergo traditional anterior colporrhaphy alone or reinforced with mesh . The low-weight monofilament polypropylene mesh was self-tailored , having four arms and being placed over the plicated fascia . Before and 2 and 12 months after surgery , participants were evaluated by physical examination , postvoidal residual urine measurement and st and ard questions covering prolapse-related symptoms . The primary outcome was recurrence of anterior vaginal prolapse at 12 months . Secondary outcomes included operative complications , symptom resolution , and postvoidal urine residual volume . RESULTS : Of the 202 women r and omly assigned , 201 were operated on ( 97 without , 104 with mesh ) . Thirty-seven women ( 38.5 % ) in the no-mesh and seven ( 6.7 % ) in the mesh group experienced a recurrence of anterior wall prolapse ( P<.001 ) at 12 months ; as a result , the number needed to treat for benefit was four . The mean ( st and ard deviation ) postvoidal residual urine volume was lower in patients with mesh than in those undergoing the traditional operation : 25 ( 26 ) mL and 41 ( 57 ) mL ( P=.01 ) . Twenty-three women ( 23 % ) with mesh and 9 ( 10 % ) with no mesh reported stress urinary incontinence ( P=.02 ) . In 18 ( 17.3 % ) , exposure of the mesh was noted , mainly asymptomatic . CONCLUSION : Anterior colporrhaphy , reinforced with , tailored mesh significantly reduced the rate of recurrence of anterior vaginal wall prolapse compared with the traditional operation , but was associated more often with stress urinary incontinence . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00420225 LEVEL OF EVIDENCE : Introduction and hypothesisThe aim of this study was to compare failure and complication rates in patients who underwent a trocar-guided vaginal mesh repair with either a non-absorbable or a partially absorbable mesh . Methods Retrospective analysis of prospect ively collected data from consecutive women undergoing either non-absorbable or partially absorbable mesh for symptomatic stage 2 prolapse or higher were evaluated at 12 months . Outcome measures included objective and subjective failure rates , patient ’s satisfaction , complications and perioperative outcomes . Results Five hundred and sixty-nine women ( 347 with non-absorbable mesh , 222 with partially absorbable mesh ) were included . Failure rates were similar in the two groups ; the re-operation rate in the untreated compartments was higher in the non-absorbable mesh group compared with the partially absorbable mesh group ( 5 % vs 1 % ) . Mesh exposure rate in the non-absorbable mesh group was 12 % and in the partially absorbable mesh group it was 5 % . Other complication and patient satisfaction rates were similar . Conclusions Non-absorbable and partially absorbable mesh demonstrated similar outcome rates at 12 months . The risk of reoperation was lower for partially absorbable mesh . The mesh exposure rate was significantly lower for the partially absorbable mesh group compared with the non-absorbable mesh group OBJECTIVE To compare the efficacy of two st and ard surgical procedures for post-hysterectomy vaginal vault prolapse in patients with levator ani avulsion . METHODS This was a single-center , r and omized interventional trial , of two st and ard surgical procedures for post-hysterectomy vaginal vault prolapse : Prolift Total vs unilateral vaginal sacrospinous colpopexy with native tissue vaginal repair ( sacrospinous fixation , SSF ) , during the period from 2008 to 2011 . Entry criteria included at least two-compartment prolapse , as well as complete unilateral or bilateral levator ani avulsion injury . The primary outcome was anatomical failure based on clinical and ultrasound assessment . Failure was defined clinical ly , according to the Pelvic Organ Prolapse Quantification system , as Ba , C or Bp at the hymen or below , and on translabial ultrasound as bladder descent to 10 mm or more below the lower margin of the symphysis pubis on maximum Valsalva maneuver . Secondary outcomes were evaluation of continence , sexual function and prolapse symptoms based on vali date d question naires . RESULTS During the study period , 142 patients who were post-hysterectomy underwent surgery for prolapse in our unit ; 72 of these were diagnosed with an avulsion injury and were offered participation in the study . Seventy patients were r and omized into two groups : 36 in the Prolift group and 34 in the SSF group . On clinical examination at 1-year follow-up , we observed one ( 3 % ) case of anatomical failure in the Prolift group and 22 ( 65 % ) in the SSF group ( P < 0.001 ) . Using ultrasound criteria , there was one ( 2.8 % ) failure in the Prolift group compared with 21 ( 61.8 % ) in the SSF group ( P < 0.001 ) . The postoperative POPDI ( Pelvic Organ Prolapse Distress Inventory ) score for subjective outcome was 15.3 in the Prolift group vs 21.7 in the SSF group ( P = 0.16 ) . CONCLUSION In patients with prolapse after hysterectomy and levator ani avulsion injury , SSF has a higher anatomical failure rate than does the Prolift Total procedure at 1-year follow-up OBJECTIVE : To estimate the effect of porcine subintestinal submucosal graft augmentation on improving anatomic and subjective rectocele repair outcomes compared with native tissue repair . METHODS : We conducted a r and omized controlled trial at two sites , including women with at least stage 2 symptomatic rectocele . Anatomic and subjective outcomes ( vaginal bulge and defecatory ) were collected 12 months postoperatively , including blinded Pelvic Organ Prolapse Quantification ( POP-Q ) examinations . Anatomic failure was defined as points Ap or Bp −1 or greater on POP-Q. Subjective failure was defined as no improvement or worsening of symptoms . We estimated number needed to treat and adjusted odds ratios ( ORs ) . Assuming graft use is associated with 93 % anatomic success , 63 women per group would be needed to detect a 20 % difference at & agr;=.05 and & bgr;=.20 . RESULTS : One hundred sixty women were r and omized ; 137 had 12-month anatomic data ( 67 graft ; 70 control ) . There was no difference in anatomic failure ( 12 % compared with 9 % , P=.5 ) , vaginal bulge symptom failure ( 3 % compared with 7 % , P=.4 , number needed to treat=26 ) or defecatory symptom failure ( 44 % compared with 45 % , P=.9 , number needed to treat=91 ) for graft compared with control , respectively . Both groups reported improvement in vaginal bulge and defecatory symptoms ( P<.05 for all ) . On multiple logistic regression , graft use was not associated with a decreased odds of anatomic failure ( adjusted OR 1.36 , 95 % confidence interval [ CI ] 0.44–4.25 ) , vaginal bulge symptoms ( adjusted OR 0.46 , 95 % CI 0.08–2.68 ) , or defecatory symptoms ( adjusted OR 0.98 , 95 % CI 0.48–2.03 ) . CONCLUSION : Although rectocele repair by either approach is associated with improved symptoms , subintestinal submucosal graft augmentation was not superior to native tissue for anatomic or subjective outcomes at 12 months . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00321867 . LEVEL OF EVIDENCE : Please cite this paper as : Vollebregt A , Fischer K , Gietelink D , van der Vaart C. Primary surgical repair of anterior vaginal prolapse : a r and omised trial comparing anatomical and functional outcome between anterior colporrhaphy and trocar‐guided transobturator anterior mesh . BJOG 2011;118:1518–1527 BACKGROUND The use of st and ardized mesh kits for repair of pelvic-organ prolapse has spread rapidly in recent years , but it is unclear whether this approach results in better outcomes than traditional colporrhaphy . METHODS In this multicenter , parallel-group , r and omized , controlled trial , we compared the use of a trocar-guided , transvaginal polypropylene-mesh repair kit with traditional colporrhaphy in women with prolapse of the anterior vaginal wall ( cystocele ) . The primary outcome was a composite of the objective anatomical design ation of stage 0 ( no prolapse ) or 1 ( position of the anterior vaginal wall more than 1 cm above the hymen ) , according to the Pelvic Organ Prolapse Quantification system , and the subjective absence of symptoms of vaginal bulging 12 months after the surgery . RESULTS Of 389 women who were r and omly assigned to a study treatment , 200 underwent prolapse repair with the transvaginal mesh kit and 189 underwent traditional colporrhaphy . At 1 year , the primary outcome was significantly more common in the women treated with transvaginal mesh repair ( 60.8 % ) than in those who underwent colporrhaphy ( 34.5 % ) ( absolute difference , 26.3 percentage points ; 95 % confidence interval , 15.6 to 37.0 ) . The surgery lasted longer and the rates of intraoperative hemorrhage were higher in the mesh-repair group than in the colporrhaphy group ( P<0.001 for both comparisons ) . Rates of bladder perforation were 3.5 % in the mesh-repair group and 0.5 % in the colporrhaphy group ( P=0.07 ) , and the respective rates of new stress urinary incontinence after surgery were 12.3 % and 6.3 % ( P=0.05 ) . Surgical reintervention to correct mesh exposure during follow-up occurred in 3.2 % of 186 patients in the mesh-repair group . CONCLUSIONS As compared with anterior colporrhaphy , use of a st and ardized , trocar-guided mesh kit for cystocele repair result ed in higher short-term rates of successful treatment but also in higher rates of surgical complications and postoperative adverse events . ( Funded by the Karolinska Institutet and Ethicon ; Clinical Trials.gov number , NCT00566917 . ) Purpose To compare the clinical effectiveness of anterior colporrhaphy versus mesh repair as surgical management of anterior vaginal prolapse . Methods Of 50 patients with ≥stage II anterior vaginal prolapse on Pelvic Organ Prolapse Quantification ( POPQ ) system who were initially approached , 44 consented and underwent surgery . They were r and omly recruited into two groups . Group I ( 23 patients ) received anterior colporrhaphy , while group II ( 21 patients ) received soft polypropylene mesh ( GYNEMESH*PS , Gynecare , Ethicon , France ) . Clinical assessment took place preoperatively and postoperatively at definite intervals . Functional and anatomical comparisons were based on comparison between preoperative and 24 months postoperative assessment s of symptoms and POPQ stages , respectively . Four patients in total did not complete the follow-up assessment s and were excluded . Results Both groups showed clinical improvement in their symptoms and POPQ staging at the end of the postoperative follow-up period . Improvement , however , was more significant in the repair with mesh group , as patients in this group reported better improvement of their prolapse symptoms , mainly vaginal bulge/pressure sensation ( P < 0.05 ) , and showed better improvement in the anatomical staging , individual POP-Q points Aa and Ba ( P < 0.01 ) , than the anterior colporrhaphy group . Group II also showed more satisfactory outcome with the general POP-Q staging ( P < 0.05 ) than group I , reflecting a better quality of life of the patients in the repair with mesh group . Conclusion Our data shows that repair with mesh is superior to anterior colporrhaphy with more satisfactory outcome to the patients . Due to the small size of our study and uncertainty of the long-term safety and resilience of the mesh , we recommend larger studies to confirm our preliminary results PURPOSE We evaluated the efficacy of the Pelvicol porcine collagen implant for preventing recurrent anterior vaginal wall prolapse in women undergoing primary surgery for pelvic organ prolapse . MATERIAL S AND METHODS This was a prospect i ve , r and omized , multicenter trial in 206 women with stage II or greater anterior vaginal wall prolapse ( point Ba -1 or greater ) according to the pelvic organ prolapse quantification system . The patients were r and omly assigned to undergo anterior vaginal repair or the same procedure with Pelvicol implant reinforcement . SPSS software was used for data analysis . RESULTS A total of 201 women were available for surgical outcome analysis , including 98 and 103 in the implant and no implant groups , respectively . All completed the 1-year followup visit . Most women were satisfied with the postoperative condition with a significant decrease in the visual analog scale score in each group ( p < 0.001 ) . Anatomical anterior recurrence ( point Ba greater than -1 ) was observed in 7 women ( 7 % ) in the implant group and in 20 ( 19 % ) in the other groups ( OR 3.13 , 95 % CI 1.26 - 7.78 , p = 0.019 ) . Additionally , there were 11 women ( 3 and 8 , respectively , or 5 % ) with posterior recurrence and 6 ( 3 per group or 3 % ) with unsatisfactory results at the upper vaginal segment . One patient who received a porcine implant had vaginal extrusion of the mesh 1 month after surgery . CONCLUSIONS Our data show that the Pelvicol implant can be easily and readily used to augment and reinforce anterior colporrhaphy . The prolapse recurrence rate was considerably lower in the implant group compared with outcomes in patients treated with simple anterior repair PURPOSE Because traditional anterior colporrhaphy can have a high recurrence rate , we assessed the recurrence rate of 3 methods of cystocele repair , including 1 ) traditional anterior colporrhaphy , 2 ) repair using porcine dermis interposition graft and 3 ) repair using polypropylene mesh . Additionally , we compared the rate of erosion of porcine dermal graft with that of polypropylene mesh . MATERIAL S AND METHODS The records of patients who underwent cystocele repair by the same urologist using porcine dermal graft , polypropylene mesh or traditional repair from January 1999 to August 2005 were review ed . Data were collected on history , physical examination , outcomes and complications . Using the Baden-Walker system a cystocele of grade 2 or higher on followup examination was considered recurrence . RESULTS A total of 119 patients underwent cystocele repair from January 1999 to August 2005 . Followup was available on 99 patients and it averaged 13.5 months ( range 2 to 46 ) . Of the patients 56 ( 57 % ) underwent cystocele repair using porcine dermal graft , 25 ( 25 % ) received polypropylene mesh and 18 ( 18 % ) underwent traditional repair . Of the 99 patients 22 ( 22 % ) had cystocele recurrence . Based on the type of repair 36 % of patients ( 20 of 56 ) with porcine dermal grafts had recurrence compared to 4 % ( 1 of 25 ) and 6 % ( 1 of 18 ) using polypropylene and traditional repair , respectively . Mean time to cystocele recurrence was 4.9 months ( range 0.5 to 20 ) . A total of 12 patients ( 21 % ) had extrusion of porcine grafts through the anterior vaginal wall incision compared to 1 ( 4 % ) with polypropylene mesh . CONCLUSIONS In our patient population the short-term failure rate for anterior vaginal wall prolapse using porcine dermis interposition graft was higher than that for traditional anterior colporrhaphy or polypropylene mesh . In addition , the incidence of vaginal extrusion of porcine graft was unacceptably high . Porcine dermis is a less suitable material for cystocele repair than polypropylene mesh or traditional anterior colporrhaphy . Prospect i ve , r and omized trials are necessary to determine the true efficacy and complication rates of these graft material s for anterior vaginal wall prolapse repair STUDY OBJECTIVE To compare the effectiveness and safety of 2 anterior transobturator mesh methods for treating anterior vaginal wall prolapse . DESIGN R and omized controlled study ( Canadian Task Force classification I ) . SETTING University hospital . PATIENTS Eighty-seven women with anterior vaginal wall prolapse stage ≥2 ( Pelvic Organ Prolapse Quantification [ POP-Q ] ) underwent an anterior transobturator mesh procedure using macropore polypropylene mesh . INTERVENTIONS Forty-five patients underwent the operation via the conventional 4-point , full-sized mesh method , and 42 patients underwent the operation via a novel 2-point , half-sized mesh method . MEASUREMENTS AND MAIN RESULTS Patient characteristics were comparable between the 2 groups . The anatomic cure rate was significantly lower in the 2-point group compared with the 4-point group at 12 months after surgery ( 87.2 % vs 100 % ; p = .03 ) . Healing abnormalities were significantly higher in the 2-point group than in the 4-point group ( 12.8 % vs 0 % ; p = .03 ) . Bladder perforation ( 2.6 % vs 0 % ) , stress urinary incontinence ( 23.1 % vs 22.5 % ) , urinary frequency ( 12.8 % vs 22.5 % ) , and voiding difficulty and dyspareunia ( 0 % vs 0 % ) were not statistically different between the 2 groups . At linear regression analysis , mean ( SD ) operation time did not differ between the 2 groups ( 74.9 [ 32.7 ] minutes vs 87.8 [ 36.7 ] minutes ; p = .11 ) . CONCLUSION Compared with the 4-point method , the 2-point anterior transobturator mesh method result ed in a lower rate of anatomic cure and a higher rate of healing abnormality OBJECTIVE The purpose of this study was to compare outcomes after anterior colporrhaphy with the use of 3 different surgical techniques . STUDY DESIGN One hundred fourteen women with anterior vaginal prolapse were r and omly assigned to undergo anterior repair by one of 3 techniques : st and ard , st and ard plus polyglactin 910 mesh , or ultralateral anterior colporrhaphy . Before and after operation , patients underwent physical examination staging of prolapse ; the International Continence Society system was used . Symptoms were assessed by question naire and visual analog scales . We defined " cure " as satisfactory ( stage I ) or optimal ( stage 0 ) outcome at points Aa and Ba . RESULTS Of 114 patients who were originally enrolled , 109 patients underwent operation , and 83 patients ( 76 % ) returned for follow-up . Mean age ( + /- SD ) was 64.7 + /- 11.1 years . At entry , 7 patients ( 7 % ) had stage I anterior vaginal prolapse ; 35 patients ( 37 % ) had stage II anterior vaginal prolapse ; 51 patients ( 54 % ) had stage III anterior vaginal prolapse ; and 2 patients ( 2 % ) had stage IV anterior vaginal prolapse . At a median length of follow-up of 23.3 months , 10 of 33 patients ( 30 % ) who were r and omly assigned to the st and ard anterior colporrhaphy group experienced satisfactory or optimal anatomic results , compared with 11 of 26 patients ( 42 % ) with st and ard plus mesh and with 11 of 24 patients ( 46 % ) with ultralateral anterior colporrhaphy . The severity of symptoms that were related to prolapse improved markedly ( preoperative score , 6.9 + /- 2.7 ; postoperative score , 1.1 + /- 0.8 ) . Twenty-three of 24 patients ( 96 % ) no longer required manual pressure to void after operation . CONCLUSION These 3 techniques of anterior colporrhaphy provided similar anatomic cure rates and symptom resolution for anterior vaginal prolapse repair . The addition of polyglactin 910 mesh did not improve the cure rate compared with st and ard anterior colporrhaphy OBJECTIVE : To report 2-year outcomes of a r and omized controlled trial comparing st and ard anterior colporrhaphy with reinforced vaginal paravaginal repair using xenograft or synthetic mesh in women with symptomatic anterior vaginal wall prolapse . METHODS : Women with stage II or greater anterior prolapse were r and omly assigned to three groups : anterior colporrhaphy , paravaginal repair with porcine dermis , or polypropylene mesh . Outcomes of prolapse stage , quality of life , degree of bother , and sexual symptoms were assessed by blinded examiners and vali date d measures at 2 years . Anatomic failure was defined as anterior prolapse at stage II or greater . Composite failure was defined as symptoms of “ bulge ” and anterior prolapse at stage II or greater . Power calculations determined 33 participants per arm would detect a 40 % difference in anatomic success between st and ard and grafted repair . & khgr;2 , Mann-Whitney U , and Student 's t tests were used for comparisons . RESULTS : Of the 99 participants enrolled , 78 ( 79 % ) completed a minimum of 2-year follow-up . Those with mesh had a significantly lower anatomic failure rate ( 18 % ) than both the porcine ( 46 % , P=.015 ) and colporrhaphy groups ( 58 % , P=.002 ) . All groups had statistically similar reductions in their prolapse and urinary symptom subscale scores . Composite failure was not statistically different between groups : 13 % colporrhaphy , 12 % porcine , and 4 % mesh . Two reoperations for anterior prolapse occurred in the porcine group . Mesh erosion rates were 14 % for the mesh group . CONCLUSION : Vaginal paravaginal repair with polypropylene mesh has the lowest anatomic failure rate when compared with that with xenograft and anterior colporrhaphy without differences in composite failures . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT0139171 . LEVEL OF EVIDENCE : Introduction and hypothesisDifferent techniques of mesh placement for cystocele repair are known . Our goal was to compare anatomical and functional outcomes of three different techniques of mesh placement over a 3-year follow-up . Methods Between March 2003 and June 2004 , 230 patients ( stage 2–4 pelvic organ prolapse ( POP ) ) were included in a prospect i ve study . For cystocele repair , mesh was implanted either with two arms into the retropubic space ( RP ) or with two to four arms into the obturator foramen ( TO ) , or fixed to the arcus tendineous fascia pelvis ( FG ) . Results Patients ' distribution is as follows : 142 TO , 32 RP , and 31 FG . Anatomical success ( cystocele < stage 2 in the POP staging system ) was clearly poorer after the retropubic free technique , with success rates of 69 % ( RP ) , 90.1 % ( TO ) , and 96.6 % ( FG ) ( p = 0.004 ) . POP distress inventory ( p < 0.005 ) and POP impact question naire scores were both significantly poorer after RP . Conclusions RP technique is less effective than TO and FG techniques Objective . To determine the long‐term objective and subjective outcomes of use of a porcine skin graft ( Pelvicol ™ ) compared with conventional colporrhaphy in recurrent pelvic organ prolapse surgery and to analyze risk factors and safety . Design . Open r and omized controlled multicenter study . Setting . Eight Swedish hospitals . Population . 135 consecutive women with recurrent cystocele and /or rectocele admitted for vaginal prolapse surgery ; 132 completed the study , 64 were r and omly allocated to receive conventional colporrhaphy and 68 to Pelvicol . Methods . Conventional anterior and posterior colporrhaphy and colporrhaphy with use of Pelvicol ™ mesh reinforcement . Clinical evaluation by means of pelvic organ prolapse quantification ( POP‐Q ) and symptom question naire preoperatively , three months and three years postoperatively . Main outcome measures . Anatomical and subjective outcome . Recurrence was defined as POP‐Q≥stage 2 . Results . At three‐month follow‐up , early recurrence/surgical failures occurred significantly more often in the Pelvicol ™ group , but at the three‐year follow‐up the recurrence rates were similar . The recurrence rates in the anterior compartment were 57–62 % and 44–23 % in the posterior compartment for the colporrhaphy and Pelvicol ™ groups , respectively . Symptoms were substantially and equally reduced in the two groups after surgery . Sexual activity and function did not seem to be affected adversely in any group . The complication rate was low . Risk factors for anatomical recurrence were age , body mass index and preoperative stage of the prolapse . Conclusions . With the surgical technique used in this study , Pelvicol ™ did not provide advantages over conventional colporrhaphy in recurrent pelvic organ prolapse concerning anatomical and subjective outcomes OBJECTIVES To determine the efficacy of grade 4 cystocele repair using the four-defect repair ( FDR ) or modified FDR with porcine xenograft matrix ( FDR+Pelvicol ) . METHODS During a 4-year period , 45 women underwent grade 4 cystocele repair . Of the 45 patients , 43 ( 95.5 % ) were available for follow-up . The mean age was 65 years . Patients presented with the following problems : grade 4 cystocele in 43 ( 100.0 % ) , stress urinary incontinence in 24 ( 55.8 % ) , urge urinary incontinence in 26 ( 60.4 % ) , and obstructive voiding symptoms in 26 ( 60.4 % ) . Patients were evaluated using the stress , emptying , anatomic , protection , and instability ( SEAPI ) test . We performed FDR in the first consecutive 24 ( 55.8 % ) and FDR+Pelvicol in the remaining 19 ( 44.2 % ) patients . Cystocele repair was accompanied by other transvaginal repair in 38 ( 88.3 % ) of the 43 patients . RESULTS The mean follow-up time was 15 months . A comparison of the preoperative and postoperative SEAPI scores of 0 , representing the absence of complaints , revealed a statistically significant improvement in all the SEAPI domains using McNemar 's test . Cystocele recurred in 3 patients ( 6.9 % ) , all in the Pelvicol subgroup . Two patients ( 4.7 % ) had postoperative urinary retention . De novo urge incontinence occurred in 2 patients ( 11.7 % ) . No infection , erosion , fistula , or vaginal stenosis have been reported . CONCLUSIONS Grade 4 cystocele repair using FDR or FDR+Pelvicol are two effective methods of cystocele repair . Although cystocele failures occurred exclusively in the Pelvicol+FDR subgroup , their small number and asymptomatic presentation did not result in statistical or clinical significance at this point . Both techniques are simple , efficacious , and well tolerated by patients . Follow-up is ongoing to evaluate the durability of the techniques OBJECTIVE To compare midterm clinical outcome using modified pelvic floor reconstructive surgery with mesh ( MPFR ) vs Prolift devices for the treatment of pelvic organ prolapse ( POP ) . STUDY DESIGN This prospect i ve observational cohort study involved 223 women with POP stages III-IV who were assigned to either MPFR ( n=131 ) or Prolift device ( n=92 ) . Outcomes were analyzed at 6 and 12 months and the last follow-up visit postoperatively . Main outcome measures included pelvic organ prolapse quantification measurement , Short Form-20 Pelvic Floor Distress Inventory ( PFDI-20 ) , Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Question naire ( PISQ ) question naires , perioperative outcomes , complications , and a personal interview about urinary and sexual symptoms . Statistical analysis included comparison of means ( Wilcoxon test or Student 's t-test ) and proportions ( Chi-square test ) . Multivariate analysis was carried out using Cox proportional hazard model . RESULTS At follow-up ( median , 36 months ; range , 17 - 58 months ) , anatomic success for MPFR and Prolift was 87.07 % and 93.41 % , respectively ( P=0.1339 ) . Both operations significantly improved quality of life , and PFDI-20 scores were lower in the Prolift group than the MPFR group ( P=0.03 ) . Complication rates did not differ significantly between the two groups and the prevalence of urinary symptoms decreased postoperatively in both groups . The cost of operation , however , was RMB ¥ 11,882.86 yuan for MPFR and ¥ 23,617.59yuan for Prolift ( P=0.00 ) . CONCLUSIONS MPFR and Prolift had comparable anatomic outcomes , Prolift had better functional outcomes than MPFR , but MPFR is much cheaper than Prolift . MPFR is an alternative , cheap and effective surgical treatment option to mesh-kits for the management for POP OBJECTIVE : To compare outcomes of anterior colporrhaphy alone to that reinforced with bovine pericardium graft . METHODS : Women with anterior vaginal wall prolapse were enrolled in a r and omized fashion in this grafted compared with nongrafted repair study . Outcome measures included pelvic organ prolapse quantification data , quality -of-life assessment , healing abnormalities , and complications . RESULTS : Ninety-four patients were enrolled . Seventy-two ( 77 % ) provided 1-year data , and 59 ( 63 % ) supplied 2-year data . Demographics and stage of prolapse were similar between groups at baseline . Postoperative complications consisted basically of low urinary tract infection and were low in both groups ( 10 in bovine pericardium graft and 16 in anterior colporrhaphy alone ) . One year after surgery , successful anterior vaginal wall support was obtained in 85.7 % of the bovine pericardium graft group and 78.4 % of anterior colporrhaphy – alone group ( P=.544 ) . For the cohort that comprised 2-year analyses , the success rate was 76.5 % for the bovine pericardium graft group and 63 % for anterior colporrhaphy – alone group ( P=.509 ) . Postoperative Urogenital Distress Inventory-6 and Pelvic Organ Prolapse – Urinary Incontinence Sexual Function Question naire-12 scores were uniformly improved over baseline in both groups . CONCLUSION : The use of bovine pericardium graft for anterior vaginal prolapse does not have higher complication rates or healing difficulties . At 1- and 2-year follow-up , anterior colporrhaphy with bovine pericardium reinforcement did not show a statistically significant improvement over colporrhaphy alone . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00860912 LEVEL OF EVIDENCE : Introduction and hypothesisThis study seeks to compare the small intestine submucosa ( SIS ) graft with traditional colporrhaphy ( TC ) for surgical treatment of anterior vaginal prolapse . Methods Subjects were r and omly assigned to SIS ( n = 29 ) or to TC ( n = 27 ) preoperatively and outcomes analyzed at 12 months postoperatively . The primary outcome was the absence of POP-Q stage ≥ II prolapse , and secondary outcome was improvement in quality of life . Data were compared with independent sample s or paired Student ’s t test . Results SIS group had 86.2 % anatomic cure compared to 59.3 % in TC ( p = 0.03 ) . SIS improved point Ba measurement significantly ( −1.93 cm versus −1.37 cm , p = 0.02 ) . Both operations significantly improved quality of life , although there were no differences between the groups . We observed a greater number of complications in the SIS group , with no infections or erosion . Conclusions SIS repair improved point Ba significantly . However , there were no differences observed in quality of life between the techniques OBJECTIVE To compare the effects of two surgical procedures for the correction of anterior vaginal wall prolapse ( AVWP ) on the lower urinary tract symptoms ( LUTS ) using symptom question naires and quality of life ( QoL ) . MATERIAL S AND METHODS One hundred women with Pelvic Organ Prolapse Quantification stage ( POP-Q ) ≥ 2 were r and omly distributed in two preoperatory groups . The first group ( mesh ) ( n = 45 ) received a polypropylene mesh ( PM ) implant and the control group ( n = 55 ) was su bmi tted to anterior colporraphy with or without synthetic sling . Postoperatory follow-up was done after 12 months . The primary objective was to compare the effect of the surgeries on LUTS using the final scores of the International Consultation on Incontinence Question naire Urinary Incontinence Short Form ( ICIQ-UI SF ) and Overactive Bladder Question naire ( OAB-V8 ) , as well as the analysis of the incapacitating urinary symptoms and ″de novo″ urinary symptoms after 12 months of surgery in both groups . RESULTS Although there was a different number of women in each group , r and omization was adequate , result ed in homogeneous groups that could be compared regarding socio demographic , clinical and gynecological ( POP-Q ) variables . Patients of both groups showed improvements regarding LUTS and QoL , whether using polypropylene mesh or not , based on the final scores of the ICIQ-UI SF and OAB-V8 question naires after 12-month follow-up . There were few incapacitating and ″de novo ″ urinary symptoms , without any significant statistical difference between both groups after 12 months of surgery . CONCLUSION There was a general improvement of LUTS and QoL in both groups after 12-month follow-up . However , there was no significant difference of LUTS , as well as the more incapacitating and ″de novo ″ urinary symptoms between both groups after 12 months of surgery To evaluate whether symptom resolution and sexual function is better after reinforcement with polypropylene mesh than with traditional anterior repair . Ninety-seven patients were r and omized to anterior colporrhaphy and 105 to an operation with mesh . Participants were evaluated up to 24 months by physical examination , st and ard questions , and question naire . The overall symptom rate did not differ between the groups , but a sensation of vaginal bulge was reported less frequently in the mesh group , the figures being 17 versus 5 ( p = 0.003 ) . The recurrence rate for the no-mesh group was 41 % and for the mesh group 11 % ( p < 0.001 ) . The dyspareunia score was statistically significantly lower in the mesh group ( p = 0.015 ) . The mesh exposure rate was 8 % . Sensation of vaginal bulge was relieved more efficiently by the mesh technique without causing dyspareunia Introduction and hypothesisIn surgery for pelvic organ prolapse ( POP ) the use of alloplastic meshes has become common . Among possible complications , mesh exposure is the most frequent problem . It is hypothesized that exposure rates are correlated to mesh weight and the amount of foreign material . Therefore , we conducted a prospect i ve open-label r and omized multicenter trial comparing a conventional polypropylene mesh ( PP ) with a partially absorbable polypropylene mesh ( PA ) for cystocele treatment . Methods A total of 200 patients with POP > stage I were r and omized either to a conventional or a partially absorbable mesh . Exposure rates were observed after 3 , 12 , and 36 months and correlated to mesh material , patient characteristics , intraoperative data , and treatment centers . Furthermore , management of mesh exposure , satisfaction with surgery , and postoperative pain were evaluated . Results At all follow-up intervals mesh exposure rate was smaller in the group of the partially absorbable mesh ( 3 months PP 11.3 % vs PA 3.2 % , p = 0.0492 ; 12 months 6.6 % vs 6.3 % ; 36 months 7.5 % vs 3.4 % ) . Over the course of time , mesh exposure was observed in 27 patients , with surgical intervention necessary in 11 patients . The rate of recurrent POP was higher ( p > 0.05 ) in patients with the partially absorbable mesh . The majority of patients were fully satisfied with the operation ( 52.8 % ) and had no pelvic floor pain ( 67.5 % ) . Conclusion In this prospect i ve , r and omized trial with a long-term follow-up there was a low exposure rate in both treatment groups with a trend toward fewer exposures in the group of the partially absorbable mesh Introduction and hypothesisOur aim was to compare anatomical and functional outcome between vaginal colposuspension and transvaginal mesh . Methods This was a prospect i ve r and omized controlled trial in a teaching hospital . Sixty-eight women with stage ≥3 anterior vaginal wall prolapse according to the Pelvic Organ Prolapse Quantification ( POP-Q ) system were assessed , r and omized , and analyzed . Patients were r and omized to anterior colporrhaphy with vaginal colposuspension ( n = 35 ) or transvaginal mesh ( n = 33 ) . Primary outcome was objective cure rate of the anterior vaginal wall , defined as POP-Q ≤1 at 2 years . Secondary outcomes were functional results , quality -of-life ( QoL ) scores , mesh-related morbidity , and onset of urinary incontinence . Results The anatomical result for point Ba was significantly better at 2 years in the mesh group ( −2.8 cm ) than in the colposuspension group ( −2.4 cm ) ( p = 0.02 ) . Concerning POP-Q stages , the anatomical success rate at 2 years was 84.4 % for colposuspension and 100 % for mesh ( p = 0.05 ) . There were 5 anatomic recurrences ( 15.6 % ) in the colposuspension group . The erosion rate was 6 % ( n = 2 ) . No significant difference was noted regarding minor complications . Analysis of QoL question naires showed overall improvement in both groups , with no significant difference between them . Conclusions The vaginal colposuspension technique of anterior vaginal wall prolapse repair gave good anatomical and functional results at 2 years . Transobturator vaginal mesh gave better 2-year anatomical results than vaginal colposuspension , with overall improvement in QoL in both groups OBJECTIVE : To compare efficacy and safety of trocar-guided tension-free vaginal mesh insertion with conventional vaginal prolapse repair in patients with recurrent pelvic organ prolapse . METHODS : Patients with recurrent pelvic organ prolapse stage II or higher were r and omly assigned to either conventional vaginal prolapse surgery or polypropylene mesh insertion . Primary outcome was anatomic failure ( pelvic organ prolapse stage II or higher ) in the treated vaginal compartments . Secondary outcomes were subjective improvement , effects on bother , quality of life , and adverse events . Question naires such as the Incontinence Impact Question naire and Urogenital Distress Inventory were administered at baseline , 6 months , and 12 months . Anatomic outcomes were assessed by an unblinded surgeon . Power calculation with & agr;=0.05 and & bgr;=0.80 indicated that 194 patients were needed . RESULTS : Ninety-seven women underwent conventional repair and 93 mesh repair . The follow-up rate after 12 months was 186 of 190 patients ( 98 % ) . Twelve months postsurgery , anatomic failure in the treated compartment was observed in 38 of 84 patients ( 45.2 % ) in the conventional group and in eight of 83 patients ( 9.6 % ) in the mesh group ( P<.001 ; odds ratio , 7.7 ; 95 % confidence interval , 3.3–18 ) . Patients in either group reported less bulge and overactive bladder symptoms . Subjective improvement was reported by 64 of 80 patients ( 80 % ) in the conventional group compared with 63 of 78 patients ( 81 % ) in the mesh group . Mesh exposure was detected in 14 of 83 patients ( 16.9 % ) . CONCLUSION : At 12 months , the number of anatomic failures observed after tension-free vaginal mesh insertion was less than after conventional vaginal prolapse repair . Symptom decrease and improvement of quality of life were equal in both groups . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00372190 . LEVEL OF EVIDENCE : OBJECTIVE To compare infracoccygeal sacropexy ( IS ) and sacrospinous suspension ( SS ) for the treatment of uterine or vault prolapse . METHODS A r and omized trial of 49 women assigned to either the IS group using IVS tape ( n=24 ) or SS group ( n=25 ) . Concomitant hysterectomy and repairs were performed as appropriate . Evaluations included prolapse staging using the POP-Q system and vali date d question naires for symptoms ( PFDI ) , quality of life ( PFIQ ) , and sexuality ( PISQ-12 ) . The primary outcome measure was postoperative pain . RESULTS Patients ' characteristics were similar in both groups . IS was quicker , easier , and less painful than SS ( P<0.01 ) . Hemorrhage or hematoma rates were similar . Neither rectal injury nor vaginal erosion occurred . Mean follow-up was 16.8 months . Prolapse cure rates , symptom scores , and quality of life were similar . Postoperative cystocele occurred in 4.8 % of women after IS and 25 % after SS ( P>0.05 ) . CONCLUSION Infracoccygeal sacropexy is equivalent to sacrospinous suspension , with a decreased rate of postoperative pain and cystocele recurrence OBJECTIVE This study was undertaken to compare outcomes of 3 different rectocele repair techniques . STUDY DESIGN One hundred six women with stage II or greater posterior vaginal wall prolapse were r and omly assigned to either posterior colporrhaphy ( n = 37 ) , site-specific rectocele repair ( n = 37 ) , or site-specific rectocele repair augmented with a porcine small intestinal submucosa graft ( Fortagen , Organogenesis , Inc , Canton , MA ; n = 32 ) . Subjects underwent a physical examination and completed 3 vali date d pelvic floor instruments at baseline and 6 months , 1 year , and 2 years after surgery . Anatomic failure was defined as pelvic organ prolapse quantitation system ( POPQ ) point Bp > or = -2 at 1 year . RESULTS Of 106 subjects who enrolled , 105 underwent surgery and of those 105 , 98 subjects returned ( 93 % ) with a mean follow-up of 17.5 + /- 7 months . After 1 year , those subjects who received graft augmentation had a significantly greater anatomic failure rate ( 12/26 ; 46 % ) than those who received site-specific repair alone ( 6/27 ; 22 % ) or posterior colporraphy ( 4/28 ; 14 % ) , P = .02 . There was a significant improvement in prolapse and colorectal scales and overall summary scores of the Pelvic Floor Distress Inventory short form 20 ( PFDI-20 ) , the Pelvic Floor Impact Question naire short form 7 ( PFIQ-7 ) after surgery in all groups ( P < .001 for each ) with no differences between groups . The proportion of subjects with functional failures was 15 % overall , and not significantly different between groups . There was no significant change in the rate of dyspareunia 1 year after surgery and there were no differences between groups . Overall sexual function as measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Question naire short form ( PISQ-12 ) improved significantly in all groups postoperatively ( P < . 001 ) , with no differences between groups . CONCLUSION Posterior colporraphy and site-specific rectocele repair result in similar anatomic and functional outcomes . The addition of a porcine-derived graft does not improve anatomic outcomes . All 3 methods of rectocele repair result in significant improvements in symptoms , quality of life , and sexual function OBJECTIVE Our aim was to evaluate the efficacy of polyglactin 910 mesh in preventing recurrent cystoceles and rectoceles . STUDY DESIGN In a prospect i ve , r and omized , controlled trial , patients undergoing vaginal reconstructive surgery with cystoceles to the hymenal ring and beyond were r and omly selected to undergo anterior and posterior colporrhaphy with or without polyglactin 910 mesh reinforcement . Results were evaluated preoperatively and at 2 , 6 , 12 , and 52 weeks postoperatively . RESULTS A total of 161 women were r and omly selected for this study . One woman was excluded at the time of surgery , and 17 women were lost to follow-up . Eighty women received mesh , and 80 did not . Both groups were found to be equivalent with respect to age , parity , concomitant surgery , and menopausal and hormone replacement status . Preoperatively 49 women had a central cystocele to the hymenal ring and 111 women had cystoceles beyond the introitus ; 91 women had a rectocele to the mid-vaginal plane , 31 to the hymenal ring , and 22 beyond the introitus . After 1 year , 30 ( 43 % ) of 70 subjects without mesh and 18 ( 25 % ) of 73 subjects with mesh had recurrent cystoceles beyond the mid-vaginal plane ( P = .02 ) . Eight women without mesh and 2 women with mesh had recurrent cystoceles to the hymenal ring ( P = .04 ) . No recurrent cystoceles beyond the hymenal ring occurred in either group . Multivariate logistic regression analysis showed concurrent slings to be associated with significantly fewer recurrent cystoceles ( odds ratio , 0.32 ; P = .005 ) , whereas the presence of mesh remained significantly predictive of fewer cystocele recurrences in this analysis . Thirteen recurrent rectoceles were noted 1 year postoperatively , with no differences between groups . CONCLUSION Polyglactin 910 mesh was found to be useful in the prevention of recurrent cystoceles OBJECTIVE To compare the anatomical and functional results of traditional anterior colporrhaphy and polypropylene mesh surgery in cystocele treatment . STUDY DESIGN Prospect i ve study conducted in the Urogynecology Clinic of Etlik Zubeyde Hanim Maternity and Women 's Health Teaching and Research Hospital between June 2006 and February 2007 . Forty patients with stage II and III cystocele according to the Pelvic Organ Prolapse Quantification system were allocated by a computer programme to conventional or mesh surgery . Twenty patients each underwent anterior colporrhaphy ( group I ) or polypropylene mesh ( Sofradim ( ® ) , Parieten ) surgery ( group II ) . Both groups were followed for 12 months . RESULTS At the end of the 12th month , anatomical cure rates were 15/20 ( 75 % ) and 19/20 ( 95 % ) in groups I and II , respectively , and the difference between the two groups was statistically significant ( p<0.05 ) . De novo stress urinary incontinence developed in one patient in group I. Mesh erosion developed postoperatively in three cases ( 15 % ) . CONCLUSION In terms of anatomical cure rates , polypropylene mesh surgery was the more successful treatment option when compared with anterior colporrhaphy at the end of 1 year follow-up Summary The effects at 2 years of polyglactin ( Vicryl ) mesh inlay and polydioxanone ( PDS ) or polyglactin ( Vicryl ) suture material on prolapse symptoms , urinary , bowel , sexual function and prolapse related Quality -of-Life ( QoL ) in women undergoing pelvic organ prolapse surgery were evaluated in a r and omised controlled trial with a 2 × 2 factorial design of Vicryl mesh ( n = 32 ) or not ( n = 34 ) and PDS ( n = 33 ) or Vicryl suture ( n = 33 ) . The response rate at 2 years was 82 % . There were no differences in the prolapse symptom scores between the r and omised groups . Prolapse-related QoL score ( mean difference : 2.05 , 95 % CI 0.19–3.91 ) and urinary incontinence score ( mean difference : 2.56 , 95 % CI 0.02–5.11 ) were significantly lower ( better ) in women who had Vicryl compared with PDS sutures . The apparent superiority of the prolapse-related QoL and urinary incontinence scores in women using Vicryl suture material ( vs PDS ) needs to be confirmed in a larger trial OBJECTIVE The purpose of this study was to show 12-month outcomes of a r and omized trial that compared vaginal prolapse repair with and without mesh . STUDY DESIGN Women with stage ≥2 prolapse were assigned r and omly to vaginal repair with or without mesh . The primary outcome was prolapse stage ≤1 at 12 months . Secondary outcomes included quality of life and complications . RESULTS All 65 evaluable participants were followed for 12 months after trial stoppage for mesh exposures . Thirty-two women had mesh repair ; 33 women had traditional repair . At 12 months , both groups had improvement of pelvic organ prolapse-quantification test points to similar recurrence rates . The quality of life improved and did not differ between groups : 96.2 % mesh vs 90.9 % no-mesh subjects reported a cure of bulge symptoms ; 15.6 % had mesh exposures , and reoperation rates were higher with mesh . CONCLUSION Objective and subjective improvement is seen after vaginal prolapse repair with or without mesh . However , mesh result ed in a higher reoperation rate and did not improve 1-year cure OBJECTIVE The objective of the study was to compare recurrence and complication rates for sacrospinous fixation ( SSF ) and prolene mesh techniques for the primary treatment of posthysterectomy vaginal vault prolapse . STUDY DESIGN Patients undergoing surgery for vault prolapse were included in a multicenter , r and omized , controlled study comparing SSF or total mesh ( Prolift ; Gynecare/Ethicon , Somerville , NJ ) . The examination included pelvic organ prolapse quantification , urodynamics , ultrasound , and quality -of-life ( QoL ) question naires before and 3 and 12 months after surgery . RESULTS Of 168 r and omized patients , 83 underwent SSF and 85 mesh repair . Prolapse recurrence after 12 months occurred in 39.4 % of the SSF group and in 16.9 % of the mesh group ( P = .003 ) . The mesh exposure rate was 20.8 % . No difference in QoL improvement as well as of de novo stress urinary incontinence and overactive bladder onset was found . CONCLUSION Mesh exposure occurrence was balanced against a lower prolapse recurrence rate in the patients undergoing mesh surgery compared with those undergoing SSF OBJECTIVES : To report 1-year outcomes of a r and omized controlled trial comparing polypropylene mesh – reinforced anterior vaginal prolapse repair with anterior colporrhaphy . METHODS : Seventy-six patients with stage II or greater anterior vaginal prolapse were r and omly assigned to either colporrhaphy or polypropylene mesh repair . The primary outcome was recurrent stage II anterior vaginal prolapse , and secondary outcomes were effects on quality of life and sexual symptom scores , operative time , blood loss , length of hospitalization , and adverse events . RESULTS : Thirty-eight women had anterior colporrhaphy , and 37 had polypropylene mesh repair . One patient allocated to mesh repair withdrew from the study before surgery . Clinical and demographic data did not differ significantly between the two treatment groups . One year after surgery , optimal and satisfactory anterior vaginal support were obtained in 21 of 38 ( 55 % ) of the colporrhaphy group and 33 of 38 ( 87 % ) of the mesh group ( P=.005 ) . Patients in both groups reported less bother after surgery in both prolapse and urinary symptoms . The rates of de novo dyspareunia were 4 of 26 ( 16 % ) and 2 of 23 ( 9 % ) in the colporrhaphy and mesh groups , respectively . Two of 37 ( 5 % ) patients had vaginal mesh extrusion . Nine anterior colporrhaphy patients would have to have recurrent anterior vaginal prolapse to prevent one vaginal mesh extrusion . Neither serious adverse events nor deaths occurred in either group . CONCLUSION : Anterior vaginal prolapse repair with polypropylene mesh reinforcement offers lower anatomic recurrence than anterior colporrhaphy at one year . However , quality of life and sexual symptoms scores improved in both groups . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00535301 LEVEL OF EVIDENCE : |
12,497 | 29,272,781 | CONCLUSIONS Patient-based pain educational programs may result in improvements of relevant patient-reported outcomes . | BACKGROUND Despite existing guidelines to assess and manage pain , the management of cancer-related pain is often suboptimal with patients often being undertreated .
Inadequate pain management may be due to patient-related barriers .
Educating patients may decrease these barriers .
However , the effect of pain education on patient-related outcomes is still unclear .
This review aim ed to study the effect of educational interventions on cancer-related pain . | OBJECTIVE This study examined the impact of a brief pain communication/education intervention on patient outcomes in breast cancer . We hypothesized that our intervention would improve patient communication and reduce misconceptions ( " Barriers " ) concerning pain management , and that patients with lower Barriers , or who perceived their physician as being more facilitative and receptive , would report better outcomes . METHODS Female breast cancer patients with persistent pain ( n=89 ) were r and omly assigned to either a 30-min in-person pain education/communication intervention or control condition and followed for 12 weeks . RESULTS Intervention group patients reported a significant decrease in pain Barriers but not in other outcomes . Overall , patients with lower barrier scores reported less distress and better emotional well-being . Patients who scored higher in active communication ( e.g. , asking questions , giving information ) reported fewer Barriers and better pain relief . Individuals who perceived their physicians as being more receptive reported better pain management while those who perceived their physicians as being both more receptive and facilitative were more satisfied with their health care . CONCLUSION A brief education/communication intervention reduced patients ' Barriers to pain management but did not impact other patient outcomes . PRACTICAL IMPLICATION S Pain outcomes may be improved by addressing patients ' pain misconceptions and emphasizing a receptive and responsive communication style Background : Pain is 1 of the most common symptoms that a cancer patient would experience . A significant barrier to positive pain management is patients ’ misconceptions regarding analgesics and inadequate use of nonpharmacological strategies as pain relief . Objective : The purpose of this study was to investigate the effectiveness of a pain management program ( PMP ) on pain intensity , use of PRN drugs and nonpharmacological strategies as pain relief , and barriers to managing pain in cancer patients . Methods : The study was conducted in the palliative care and hospice ward of a public hospital in Hong Kong . Patients were r and omized to either an experimental group ( receiving the PMP ) or a control group ( routine care ) . There were 38 hospitalized patients , with 20 ( 13 males and 7 females ) in the experimental group and 18 ( 11 males and 7 females ) in the control group ; mean age was 61.95 years ( experimental group ) to 63.94 years ( control group ) . Results : Upon the completion of PMP , pain scores were significantly reduced in both groups , yet patients in the experimental group showed a significant increase in the use of PRN analgesics and nonpharmacological strategies to relieve pain ( P < .05 ) and significantly reduce barriers to managing their cancer pain ( P < .05 ) compared with the control group . Conclusion : Cancer patients should be empowered with pain management education to gain knowledge and correct misconceptions in managing their cancer pain . Implication s for Practice : Integration of the PMP into routine clinical work may help to improve the st and ard of care for cancer patients . It is recommended to provide pain management education to all cancer patients Introduction The prevalence of pain in patients with cancer is still too high . Factors relating to ineffective pain treatment fall into three categories : the health care system , professional care providers , and patients . In patients , various barriers lead to noncompliance . Previous educational interventions have increased their knowledge of pain and decreased short-term pain levels . In this r and omized controlled trial , the authors investigated how an intensive home-based education program given by nurses affected short-term and long-term pain levels . Material s and methods One hundred and twenty cancer patients were r and omized to receive either the pain education program ( PEP ) or usual care . Pain , knowledge , quality of life , anxiety , and depression were measured at baseline and after 4 and 8 weeks . In the intervention group , effects on symptom levels were communicated to the treating physician . Results The level of pain had decreased at 4 weeks , but not at 8 weeks . Significant decreases in pain only persisted in those patients with a high pain score at baseline . Knowledge of pain significantly increased in the intervention group . No correlation was found between increased pain knowledge and decreased pain levels . Conclusions The PEP given by nurses lowered pain intensity levels in cancer patients and increased their knowledge of pain . More attention should be paid to patient education and to communication between patients and health professionals regarding pain and pain management PURPOSE / OBJECTIVES To test the effectiveness of two interventions compared to usual care in decreasing attitudinal barriers to cancer pain management , decreasing pain intensity , and improving functional status and quality of life ( QOL ) . DESIGN R and omized clinical trial . SETTING Six outpatient oncology clinics ( three Veterans Affairs [ VA ] facilities , one county hospital , and one community-based practice in California , and one VA clinic in New Jersey ) Sample : 318 adults with various types of cancer-related pain . METHODS Patients were r and omly assigned to one of three groups : control , st and ardized education , or coaching . Patients in the education and coaching groups viewed a video and received a pamphlet on managing cancer pain . In addition , patients in the coaching group participated in four telephone sessions with an advanced practice nurse interventionist using motivational interviewing techniques to decrease attitudinal barriers to cancer pain management . Question naires were completed at baseline and six weeks after the final telephone calls . Analysis of covariance was used to evaluate for differences in study outcomes among the three groups . MAIN RESEARCH VARIABLES Pain intensity , pain relief , pain interference , attitudinal barriers , functional status , and QOL . FINDINGS Attitudinal barrier scores did not change over time among groups . Patients r and omized to the coaching group reported significant improvement in their ratings of pain-related interference with function , as well as general health , vitality , and mental health . CONCLUSIONS Although additional evaluation is needed , coaching may be a useful strategy to help patients decrease attitudinal barriers toward cancer pain management and to better manage their cancer pain . IMPLICATION S FOR NURSING By using motivational interviewing techniques , advanced practice oncology nurses can help patients develop an appropriate plan of care to decrease pain and other symptoms BACKGROUND Inadequate adherence to prescribed analgesics may be one of the reasons why patients with cancer experience unrelieved pain . Adherence is directly influenced by patients ' barriers about pain management . Patient pain education programs ( PEPs ) have been developed to reduce patients ' barriers and increase patients ' adherence to their analgesics . The purpose of this article was to evaluate patients ' adherence in patients receiving a pain consult and patient pain education in comparison with patients receiving st and ard pain treatment ( st and ard care [ SC ] ) , to better explore the difficulties in medication adherence in cancer-related pain and the effects of PEP . METHODS In 54 adult out patients with cancer-related pain , patients ' adherence to the prescribed around-the-clock analgesics was measured with a Medication Event Monitoring System , in the following time intervals : weeks 1 and 2 , weeks 3 and 4 , and weeks 7 and 8 after r and omization . Adherence was differentiated into taking adherence , taking the correct dose , and taking analgesics at the right time intervals . RESULTS Taking adherence increased in the intervention group compared to baseline ( from 91 % to 93 % ) and decreased in the SC group ( from 85 % to 78 % ; P < 0.05 ) . At the end of the study , more patients in the intervention group took their analgesics at the right intervals ( 78 % ) than did patients in the SC group ( 64 % , P < 0.05 ) . During the study , patients were more adherent to opioids than to World Health Organization step 1 analgesics . CONCLUSION The combined intervention can increase adherence . The true problem in pain management is that patients do not take their prescribed analgesics at the right time intervals . With the detailed adherence information from this study , it is possible to further tailor patient education to the individual patient ABSTRACT Cancer pain management can be improved by overcoming patients ’ attitudinal barriers to reporting pain and using analgesics . A simple cost‐effective barriers intervention design ed to reach a large number of persons with cancer has not yet been tested . Such an intervention should be tested against barriers ’ assessment ‐alone , as well as no‐treatment control . The purpose of this study was to test the efficacy and the cost effectiveness of a tailored barriers intervention ( TBI ) , an educational intervention tailored to participants ’ attitudinal barriers toward reporting pain and using analgesics . This was a r and omized three‐group ( TBI , assessment ‐alone , or control ) trial with measures at baseline and 28 days later conducted at the North Central and Heartl and offices of the Cancer Information Service ( CIS ) , an NCI program that provides information to persons seeking answers to cancer‐related questions . Participants ( 1256 adult CIS callers diagnosed with cancer with moderate to severe pain in the past week ) joined the study and were r and omized . Of these participants , 970 ( 77.23 % ) provided follow‐up data . The TBI consisted of educational messages tailored to each participant ’s attitudinal barriers , delivered orally over the telephone , followed by a printed mailed copy . The outcome measures were attitudinal barriers to pain management , as well as pain outcomes ( duration , severity , and interference with life activities ) . At follow‐up the TBI group had significantly lower attitudinal barriers scores compared to assessment ‐alone and control , but the groups did not differ on the pain outcome variables . TBI and assessment ‐alone had similar cost effectiveness . The TBI needs to be strengthened to achieve reductions in pain severity & NA ; St and ard guidelines for cancer pain treatment routinely recommend training patients to reduce barriers to pain relief , use medications appropriately , and communicate their pain‐related needs . Methods are needed to reduce professional time required while achieving sustained intervention effectiveness . In a multisite , r and omized controlled trial , this study tested a pain training method versus a nutrition control . At six oncology clinics , physicians ( N = 22 ) and nurses ( N = 23 ) enrolled patients ( N = 93 ) who were over 18 years of age , with cancer diagnoses , pain , and a life expectancy of at least 6 months . Pain training and control interventions were matched for material s and method . Patients watched a video followed by about 20 min of manual‐st and ardized training with an oncology nurse focused on review ing the printed material and adapted to individual concerns of patients . A follow‐up phone call after 72 h addressed individualized treatment content and pain communication . Assessment s at baseline , one , three , and 6 months included barriers , the Brief Pain Inventory , opioid use , and physician and nurse ratings of their patients ’ pain . Trained versus control patients reported reduced barriers to pain relief ( P < .001 ) , lower usual pain ( P = .03 ) , and greater opioid use ( P < .001 ) . No pain training patients reported severe pain ( > 6 on a 0–10 scale ) at 1‐month outcomes ( P = .03 ) . Physician and nurse ratings were closer to patients ’ ratings of pain for trained versus nutrition groups ( P = .04 and < .001 , respectively ) . Training efficacy was not modified by patient characteristics . Using video and print material s , with brief individualized training , effectively improved pain management over time for cancer patients of varying diagnostic and demographic groups The purpose of this r and omized controlled study was to assess the effects of a structured pain education program on the pain experience of hospitalized cancer patients . Eligible cancer pain patients were r and omly assigned to either an experimental group ( receiving pain education 10–15 min per day for 5 days , n=15 ) or a st and ard care control group ( n=15 ) . The effects of the intervention on six pain-related variables were evaluated using three instruments . Pain intensity , pain interference with daily life , negative beliefs about opioids , beliefs about endurance of pain , pain catastrophizing ( an individual ’s tendency to focus on and exaggerate the threat value of painful stimuli and negatively evaluate his or her own ability to deal with pain ) , and sense of control over pain were evaluated by the Brief Pain Inventory — Short Form Taiwanese version ( BPI-T ) , Pain and Opioid Analgesic Beliefs Scale — Cancer ( POABS-CA ) , and the Catastrophizing subscale and the sense of control over pain measure from the Coping Strategies Question naire ( CSQ ) . The results indicated that , after completing treatment , patients who had received structured pain education had significantly less pain intensity on average , negative pain beliefs regarding opioids , pain endurance beliefs , and pain catastrophizing than patients in the control group . In addition , patients in the pain education group showed a significant increase in their sense of control over pain . These preliminary results strongly suggest that structured pain education can effectively improve the pain experience of hospitalized cancer patients and should be further implemented clinical ly The persistence of negative attitudes towards cancer pain and its treatment suggests there is scope for identifying more effective pain education strategies . This r and omized controlled trial involving 189 ambulatory cancer patients evaluated an educational intervention that aim ed to optimize patients ' ability to manage pain . One week post-intervention , patients receiving the pain management intervention ( PMI ) had a significantly greater increase in self-reported pain knowledge , perceived control over pain , and number of pain treatments recommended . Intervention group patients also demonstrated a greater reduction in willingness to tolerate pain , concerns about addiction and side effects , being a " good " patient , and tolerance to pain relieving medication . The results suggest that targeted educational interventions that utilize individualized instructional techniques may alter cancer patient attitudes , which can potentially act as barriers to effective pain management CONTEXT Published literature has not defined the effectiveness of st and ardized educational tools that can be self-administered in the general oncology population with pain . OBJECTIVES We sought to determine if an educational intervention consisting of a video and /or booklet for adults with cancer pain could improve knowledge and attitudes about cancer pain management , pain levels , pain interference , anxiety , quality of life , and analgesic use . METHODS Eligible participants had advanced cancer , a pain score > /=2 of 10 in the last week , English proficiency , an estimated prognosis of more than one month , and were receiving outpatient cancer treatment at participating hospitals . Participants completed baseline assessment s and then were r and omly allocated to receive a booklet , a video , both , or neither , in addition to st and ard care . Outcome measures at two and four weeks included the Barriers Question naire ( BQ ) , Brief Pain Inventory , Global Quality of Life Scale , and Hospital Anxiety and Depression Scale . Adequacy of analgesia and severity of pain were assessed with the Pain Management Index and a daily pain diary . RESULTS One hundred fifty-eight participants were recruited from 21 sites over 42 months . Baseline mean barriers scores were lower than reported in previous Australian studies at 1.33 ( st and ard deviation : 0.92 ) . Mean average pain and worst pain scores improved significantly in patients receiving both the video and booklet by 1.17 ( st and ard error [ SE ] : 0.51 , P=0.02 ) and 1.12 ( SE : 0.57 , P=0.05 ) , respectively , on a 0 - 10 scale . The addiction subscale of the BQ score was improved by 0.44 ( SE : 0.19 ) for participants receiving any part of the intervention ( P=0.03 ) . CONCLUSION Provision of a video and /or booklet for people with cancer pain was a feasible and effective adjunct to the management of cancer pain BACKGROUND We compared the effectiveness and cost of a pain screening and treatment program , with usual care in head and neck cancer patients with significant pain . METHODS Patients were screened for the presence of pain and then r and omly assigned to either an intervention group , consisting of a pain treatment protocol and an education program , or to usual care . Primary outcome was change in the Pain Severity Index ( PSI ) over three months . RESULTS We screened 1074 patients of whom 156 were r and omized to either intervention or usual care . Mean PSI was reduced over three months in both groups , with no significant difference between the two groups . The Pain Management Index ( PMI ) at three months , was significantly improved in the intervention group compared with usual care ( P<0.001 ) , as was Patient Satisfaction ( mean difference in scores was statistically significant : -0.30 [ -0.60 to -0.15 ] ) . All subjects reported clinical ly significant levels of anxiety and depression throughout the study . Treatment costs were significantly higher for intervention ( mean=£400 ) compared with usual care ( £ 200 ) , with a low likelihood of being cost-effective . CONCLUSIONS There was no difference in the Pain Severity Index between the two groups . However there were significant improvements in the intervention group in patient satisfaction and PMI . The pain screening process itself was effective . Sufficient benefit was demonstrated as a result of the intervention to allow continued development of pain treatment pathways , rather than allowing pain treatment to be left to nonformalised ad hoc arrangements Summary This trial reveals the positive impact of a nursing intervention to improve patients ' self‐management of cancer pain and reduce care transition‐related problems . ABSTRACT Patients ' self‐management skills are affected by their knowledge , activities , and attitudes toward pain management . This trial aim ed to test the Self Care Improvement through Oncology Nursing (SCION)‐PAIN program , a multimodular structured intervention to reduce patients ' barriers to self‐management of cancer pain . Two hundred sixty‐three patients with diagnosed malignancy , pain > 3 days , and average pain ≥ 3/10 participated in a cluster‐r and omized trial on 18 wards in 2 German university hospitals . Patients on the intervention wards received , in addition to st and ard pain treatment , the SCION‐PAIN program consisting of 3 modules : pharmacologic , nonpharmacologic pain management , and discharge management . The intervention was conducted by specially trained cancer nurses and included components of patient education , skills training , and counseling . Starting with admission , patients received booster sessions every third day and one follow‐up telephone counseling session within 2 to 3 days after discharge . Patients in the control group received st and ard care . Primary end point was the group difference in patient‐related barriers to self‐management of cancer pain ( Barriers Question naire – BQ II ) 7 days after discharge . The SCION‐PAIN program result ed in a significant reduction of patient‐related barriers to pain management 1 week after discharge from the hospital : mean difference on BQ II was −0.49 points ( 95 % confidence interval −0.87 points to −0.12 points ; P = 0.02 ) . Furthermore , patients showed improved adherence to pain medication ; odds ratio 8.58 ( 95 % confidence interval 1.66–44.40 ; P = 0.02 ) . A post hoc analysis indicated reduced average and worst pain intensity as well as improved quality of life . This trial reveals the positive impact of a nursing intervention to improve patients ' self‐management of cancer pain BACKGROUND The European Pain in Cancer survey sought to increase underst and ing of cancer-related pain and treatment across Europe . PATIENTS AND METHODS Patients with all stages of cancer participated in a two-phase telephone survey conducted in 11 European countries and Israel in 2006 - 2007 . The survey screened for patients experiencing pain at least weekly , then r and omly selected adult patients with pain of at least moderate intensity occurring several times per week for the last month completed a detailed attitudinal question naire . RESULTS Of 5084 adult patients contacted , 56 % suffered moderate-to-severe pain at least monthly . Of 573 patients r and omly selected for the second survey phase , 77 % were receiving prescription-only analgesics , with 41 % taking strong opioids either alone or with other drugs for cancer-related pain . Of those prescribed analgesics , 63 % experienced breakthrough pain . In all , 69 % reported pain-related difficulties with everyday activities ; however , 50 % believed that their quality of life was not considered a priority in their overall care by their health care professional . CONCLUSIONS Across Europe and Israel , treatment of cancer pain is suboptimal . Pain and pain relief should be considered integral to the diagnosis and treatment of cancer ; management guidelines should be revised to improve pain control in patients with cancer The purpose of this r and omized controlled study was to investigate the effect of a pain education program ( PEP ) on pain intensity , patients ' satisfaction with pain treatment , and patient-related barriers to pain management among Turkish patients with cancer . The study was conducted in a sample of 40 patients who were hospitalized for cancer and experiencing pain . The patients were equally r and omized to either a PEP or a control group . The data were collected by means of the McGill Pain Question naire , the Numeric Rating Scale , and the Barrier Question naire-Revised . After the completion of the question naires at the first interview , patients in the PEP group received pain education using a pain educational booklet and an explanatory slide program that discussed the booklet 's content with the patients . Patients in the control group received routine clinical care . The question naires were reapplied to the patients in both groups after 2 , 4 , and 8 weeks . Participation in a PEP was associated with decreased pain intensity scores for " present " and " least pain " during weeks 2 , 4 , and 8 ( p < .05 ) . Similarly , there were significant differences between the groups with respect to weeks 2 , 4 , and 8 satisfaction with pain treatment ( p < .05 ) . At the end of second week , the total BQ-r score decreased significantly in the PEP group from 2.12 to 1.29 compared with 2.30 to 2.28 in the control group ( p < .001 ) . The findings suggest that the PEP decreases pain intensity , improves satisfaction with treatment , and decreases barriers about cancer pain management in cancer patients . Incorparation of PEP into the st and ard of care for cancer patients with pain may improve the quality of pain management The authors have examined the effects of coaching sensory self-monitoring and reporting on pain-related variables in patients with lung cancer . R and omly assigned to coached or not-coached groups , 215 patients have their interactions with their providers audiotaped and complete study measures pre- and postintervention . Of the 151 patients who complete the 4-week study , those coached are more likely than those not coached to give their providers unsolicited sensory pain information and to mention it before their providers ask for it . The mean number of pain parameters discussed during the audiotaped clinic visit is statistically larger at study end for the coached group . Scores for analgesic adequacy , all pain indices except one , anxiety , depression , and catastrophizing coping are not significantly different . Although coaching increases the amount of pain data communicated to providers by patients with lung cancer , the magnitude is small and does not lead to improved adequacy of analgesics prescribed for each patient ’s pain level The purpose of this study was to determine if continued access to information following a baseline pain education program would increase knowledge and positive beliefs about cancer pain management , thus result ing in improved pain control during a 6-month follow-up period . Patients with cancer-related pain and their primary caregivers received a brief pain education program , and were then r and omized into one of three information groups : a ) usual care , b ) pain hot line , and c ) weekly provider-initiated follow-up calls for 1 month post-education . Sixty-four patients and their primary caregivers were recruited . Both patients and caregivers showed an improvement in knowledge and beliefs after the baseline pain education program . Continued access to pain information with either the pain hot line or provider-initiated weekly follow-up calls did not affect long-term outcomes of pain intensity , interference because of pain , adequacy of analgesics used , or pain relief . In addition , long-term outcomes did not differ between patients who had improvement and those who showed decline in knowledge and beliefs pre-post education . These findings suggest that a brief pain education program can improve knowledge and beliefs of both patient and primary caregiver . Continued access to pain related information using either a patient- or provider-initiated format did not affect long-term pain outcomes & NA ; We aim ed to determine the effectiveness of a lay‐administered tailored education and coaching ( TEC ) intervention ( aim ed at reducing pain misconceptions and enhancing self‐efficacy for communicating with physicians ) on cancer pain severity , pain‐related impairment , and quality of life . Cancer patients with baseline “ worst pain ” of ⩾4 on a 0–10 scale or at least moderate functional impairment due to pain were r and omly assigned to TEC or enhanced usual care ( EUC ) during a telephone interview conducted in advance of a planned oncology office visit ( 265 patients r and omized to TEC or EUC ; 258 completed at least one follow‐up ) . Patients completed question naires before and after the visit and were interviewed by telephone at 2 , 6 , and 12 weeks . Mixed effects regressions were used to evaluate the intervention adjusting for patient , practice , and site characteristics . Compared to EUC , TEC was associated with increased pain communication self‐efficacy after the intervention ( P < .001 ) ; both groups showed significant ( P < .0001 ) , similar , reductions in pain misconceptions . At 2 weeks , assignment to TEC was associated with improvement in pain‐related impairment ( −0.25 points on a 5‐point scale , 95 % confidence interval −0.43 to −0.06 , P = .01 ) but not in pain severity ( −0.21 points on an 11‐point scale , −0.60 to 0.17 , P = .27 ) . The improvement in pain‐related impairment was not sustained at 6 and 12 weeks . There were no significant intervention by subgroup interactions ( P > .10 ) . We conclude that TEC , compared with EUC , result ed in improved pain communication self‐efficacy and temporary improvement in pain‐related impairment , but no improvement in pain severity . Compared with control , tailored education and coaching for patients with cancer‐related pain improved communication self‐efficacy and reduced pain‐related impairment in the short term but had no sustained benefits PURPOSE To determine the effectiveness of a multicomponent clinical intervention to reduce pain in out patients with cancer . METHODS AND MATERIAL S Sixty-four patients were r and omly assigned to receive either a clinical intervention including an information session , the use of a pain diary , and the possibility to contact a physician to adjust the pain medication , or the usual treatment of pain by the staff radiation oncologist . All patients reported their average and worst pain levels at baseline and 2 and 3 weeks after the start of the intervention . RESULTS The study groups were similar with respect to their baseline characteristics and pain levels at r and omization . After 3 weeks , the average and worst pain experienced by patients r and omized to the clinical intervention group was significantly inferior to the average pain experienced by patients in the control group ( 2.9/10 vs. 4.4/10 and 4.2/10 vs. 5.5/10 , respectively ) . Results showed that the experimental group patients decreased their pain levels more than the control group patients did over time . CONCLUSION An intervention including patient education , a pain diary , and defining a procedure for therapeutic adjustments can be effective to improve pain relief in out patients with cancer PURPOSE / OBJECTIVES To evaluate the effectiveness of a psychoeducational program ( i.e. , PRO-SELF Pain Control Program ) compared to st and ard care in increasing patients ' knowledge regarding cancer pain management . DESIGN R and omized clinical trial . SETTING Seven outpatient setting s in northern California . SAMPLE 174 out patients with cancer and pain from bone metastasis . METHODS Following r and omization into either the PRO-SELF or st and ard care group , patients completed the Pain Experience Scale ( PES ) prior to and at the completion of the intervention . MAIN RESEARCH VARIABLES Total and individual item scores on the PES . FINDINGS Total PES knowledge scores increased significantly in the PRO-SELF group ( 21 % ) compared to the st and ard care group ( 0.5 % ) . Significant improvements in knowledge scores for patients in the PRO-SELF group were found on five of the nine PES items when compared to baseline scores . CONCLUSIONS The PRO-SELF Pain Control Program was an effective approach to increase patients ' knowledge of cancer pain management . IMPLICATION S FOR NURSING The use of a structured paper- and -pencil question naire , such as the PES , as part of a psychoeducational intervention provides an effective foundation for patient education in cancer pain management . Oncology nurses can use patients ' responses to this type of question naire to individualize the teaching and to spend more time on the identified knowledge deficits . This individualized approach to education about pain management may save staff time and improve patient outcomes PURPOSE Previous studies found that African American and Hispanic cancer patients are at risk for undertreatment of pain . We evaluated the efficacy of a pain education intervention for underserved minority patients . PATIENTS AND METHODS Ninety-seven underserved African American and Hispanic out patients with cancer-related pain were enrolled onto a r and omized clinical trial of pain management education . The patients in the education group received a culture-specific video and booklet on pain management . The control group received a video and booklet on nutrition . A research nurse met with each patient to review the material s. We measured changes in pain intensity and pain-related interference 2 to 10 weeks after the intervention , as well as changes in quality of life , perceived pain control , functional status , analgesics , and physician pain assessment s. RESULTS Physicians underestimated baseline pain intensity and provided inadequate analgesics for more than 50 % of the sample . Although the ratings for pain intensity and pain interference decreased over time for both groups , there was no statistically significant difference between groups . Pain education did not affect quality of life , perceived pain control , or functional status . African American patients in the education but not the control group reported a significant decrease in pain worst ratings from baseline to first follow-up ( P < .01 ) , although this decrease was not maintained at subsequent assessment s. CONCLUSION Brief education had limited impact on pain outcomes for underserved minority patients , suggesting that more intensive education for patients and interventions for physicians are needed & NA ; The effectiveness of a Pain Education Program in cancer patients with chronic pain offered by nurses was investigated in a r and omized controlled clinical trial . A multi‐ method approach was used in which verbal instruction , written material , an audio cassette tape , and the use of a pain diary were combined to inform and instruct patients about pain and pain management . The Pain Education Program was tailored to the needs of the individual patient and consisted of three elements : ( 1 ) educating patients about the basic principles regarding pain and pain management ; ( 2 ) instructing patients how to report their pain in a pain diary ; and ( 3 ) instructing patients how to communicate about pain and how to contact health care providers . Following pretesting in 313 patients , patients who needed district nursing and who did not need district nursing at home were r and omly assigned to a control or intervention group . Intervention group patients received the Pain Education Program in the hospital , and 3 and 7 days postdischarge by telephone ; this was done by nurses who were specially trained as pain counselors . Follow‐up assessment s were at 2 , 4 and 8 weeks postdischarge . Results of the pretest showed that many patients lacked knowledge about pain and pain management . The majority of pain topics had to be discussed . The Pain Education Program proved to be feasible : 75.0 % of the patients had read the entire pain brochure , 55.7 % had listened to the audio cassette , and 85.6 % of pain scores were completed in the pain diary . Results showed a significant increase in pain knowledge in patients who received the Pain Education Program and a significant decrease in pain intensity . However , pain relief was mainly found in the intervention group patients without district nursing . It can be concluded that the tailored Pain Education Program is effective for cancer patients in chronic pain . The use of the Pain Education Program by nurses should be seriously considered on oncology units PURPOSE An estimated 42 % of cancer patients suffer from poorly controlled pain , in part because of patient-related barriers to pain control . The objective of this study was to evaluate the effect of an individualized education and coaching intervention on pain outcomes and pain-related knowledge among out patients with cancer-related pain . PATIENTS AND METHODS English-speaking cancer patients ( 18 to 75 years old ) with moderate pain over the past 2 weeks were r and omly assigned to the experimental ( n = 34 ) or control group ( n = 33 ) . Experimental patients received a 20-minute individualized education and coaching session to increase knowledge of pain self-management , to redress personal misconceptions about pain treatment , and to rehearse an individually scripted patient-physician dialog about pain control . The control group received st and ardized instruction on controlling pain . Data on average pain , functional impairment as a result of pain , pain frequency , and pain-related knowledge were collected at enrollment and 2-week follow-up . RESULTS At baseline , there were no significant differences between experimental and control groups in terms of average pain , functional impairment as a result of pain , pain frequency , or pain-related knowledge . At follow-up , average pain severity improved significantly more among experimental group patients than among control patients ( P = .014 ) . The intervention had no statistically significant impact on functional impairment as a result of pain , pain frequency , or pain-related knowledge . CONCLUSION Compared with provision of st and ard educational material s and counseling , a brief individualized education and coaching intervention for out patients with cancer-related pain was associated with improvement in average pain levels . Larger studies are needed to vali date these effects and eluci date their mechanisms OBJECTIVE To determine the efficacy in overcoming attitudinal barriers to reporting cancer pain and using analgesics of an educational intervention presented to patients accompanied by a significant other ( SO ) as compared with patients alone . DESIGN Patient-SO pairs ( N = 161 ) were r and omized to the dyad condition ( patient and SO received the intervention ) , solo condition ( patient received the intervention ) , or care as usual . Dyad and solo conditions received the intervention at baseline ( T1 ) and 2 and 4 weeks later . MAIN OUTCOME MEASURES Patients ' and SOs ' attitudes about analgesic use and patients ' pain outcomes ( pain severity , pain relief , interference with life , negative mood , and global quality of life [ QOL ] ) at T1 , 5 weeks later ( T2 ) , and 9 weeks later ( T3 ) . RESULTS Completers ' analyses revealed no significant differences between groups at T2 . At T3 , patients in the dyad and the solo groups showed greater decreases in attitudinal barriers as compared with controls . T1-T3 changes in patients ' barriers mediated between the dyad and solo interventions and pain severity , pain relief , pain interference , negative mood , and global QOL . CONCLUSION The intervention was no more efficacious when it was presented to dyads than to patients alone . Conditions under which SOs should be included in interventions need to be determined PURPOSE This r and omized clinical trial tested the effectiveness of the PRO-SELF Pain Control Program compared with st and ard care in decreasing pain intensity scores , increasing appropriate analgesic prescriptions , and increasing analgesic intake in oncology out patients with pain from bone metastasis . PATIENTS AND METHODS Patients were r and omly assigned to the PRO-SELF intervention ( n = 93 ) or st and ard care ( n = 81 ) . Patients in the st and ard care arm were seen by a research nurse three times and were called three times by phone between the home visits . PRO-SELF group patients were seen by specially trained intervention nurses and received a psychoeducational intervention , were taught how to use a pillbox , and were given written instructions on how to communicate with their physician about unrelieved pain and the need for changes in their analgesic prescriptions . Patients were coached during two follow-up home visits and three phone calls on how to improve their cancer pain management . RESULTS Pain intensity scores decreased significantly from baseline ( all P < .0001 ) in the PRO-SELF group ( ie , least pain , 28.4 % ; average pain , 32.5 % ; and worst pain , 27.0 % ) compared with the st and ard care group ( ie , least increased by 14.6 % , average increased by 1.9 % , and worst decreased by 1.2 % ) . The percentage of patients in the PRO-SELF group with the most appropriate type of analgesic prescription increased significantly from 28.3 % to 37.0 % ( P = .008 ) compared with a change from 29.6 % to 32.5 % in the st and ard care group . CONCLUSION The use of a psychoeducational intervention that incorporates nurse coaching within the framework of self-care can improve the management of cancer pain PURPOSE OF THE RESEARCH This paper reports findings from a r and omized controlled pilot study evaluating the PRO-SELF Plus Pain Control Program , a U.S.-developed cancer pain self-management intervention , regarding feasibility and effect sizes in a German patient sample . METHODS AND SAMPLE Thirty-nine German oncology out patients were r and omized to intervention ( n = 19 ) and control ( n = 20 ) groups . The intervention group received the PRO-SELF Plus Pain Control Program in 6 visits and 4 phone calls a 10-week period . The control group received st and ard education and care . The intervention employed three key strategies : information provision , skills building , and nurse coaching . Primary outcomes were changes in average and worst pain intensity . Secondary outcomes included changes in pain-related knowledge , opioid intake , and self-efficacy . Data were collected at enrollment , then at 6 , 10 , 14 , and 22 weeks . KEY RESULTS The group-by-time effect showed a statistically significant increase in knowledge ( week 10 : p = 0.04 ; week 22 : p < 0.01 ) . Despite slight reductions in average and worst pain , no statistically significant changes were found for pain , opioid intake , or self-efficacy . CONCLUSIONS This study is the first to evaluate and demonstrate the feasibility of a U.S.-developed cancer pain self-management intervention in a German patient population . Pain self-management related knowledge improved significantly and effect sizes for pain reduction were determined . Findings from this pilot RCT provide the basis for planning a larger RCT . CLINICAL TRIAL REGISTRATION NUMBER NCT00920504 In a prospect i ve study of 313 Dutch cancer patients with chronic pain , the practice of pain treatment was evaluated by means of Donabedian 's structure-process- outcome framework . The practice of pain treatment was assessed by : ( 1 ) structural re sources , describing the setting in which pain treatment is provided ; ( 2 ) process components , which describe the clinical practice ; and ( 3 ) outcome measures , which refer to patients ' pain intensity , patient satisfaction , or composite pain management index scores . Results showed that 31.4 - 59.8 % of the cancer pain patients received less than optimal pain treatment . Although pain education and refresher courses for health care providers are scarce , structural re sources were not the major cause of the suboptimal level of pain treatment . Rather , the major cause was the process components . Only 36.4 % of the patients received strong opioids ; 23.1 % received analgesics " as needed . " Patients ' pain knowledge was far from optimal ( 54.8 on a 0 - 100 scale ) , and written pain information was given to only 15.8 % of the patients . After discharge , only 36.8 % of the district nurses were informed about patients ' pain . These results emphasize that continuing efforts to improve the practice of pain treatment are needed Background : The undertreatment of cancer pain remains a significant clinical problem . Objective : The aim of this r and omized controlled trial was to evaluate the efficacy of the PRO-SELF Pain Control Program that was modified for Norwegian cancer patients in decreasing pain and increasing opioid intake compared with control care . Interventions / Methods : Oncology out patients with pain from bone metastasis were r and omized into the PRO-SELF ( n = 87 ) or control ( n = 92 ) groups . A nurse visited patients in the PRO-SELF group in their home at weeks 1 , 3 , and 6 and conducted telephone interviews at weeks 2 , 4 , and 5 . Patients in both groups completed a daily diary of pain intensity ratings and analgesic intake . Results : For both groups , significant decreases in pain intensity scores and in hours per day in pain ( both , P < .001 ) were found over the 6 weeks of the study . However , no significant group × time interactions were found for any of the pain measures . In both groups , total dose of opioid taken increased over time . However , no significant group × time interactions were found for changes over time in the total dose , around-the-clock dose , or as-needed dose of opioid analgesics taken . Conclusions : Possible reasons for the lack of efficacy include an inadequate dose of the psychoeducational intervention , inadequate changes in analgesic prescriptions , and /or the impact of attention provided to the control group . Implication s for Practice : Coaching , nursing support , and the use of a pain diary may be important interventions to reduce pain intensity Summary A pain consultation combined with a pain education program significantly improves pain , daily interference , and patient adherence in oncology out patients compared with st and ard care . ABSTRACT Pain education programs ( PEP ) and pain consultations ( PC ) have been studied to overcome patient‐related and professional‐related barriers in cancer pain management . These interventions were studied separately , not in combination , and half of the studies reported a significant improvement in pain . Moreover , most PEP studies did not mention the adequacy of pain treatment . We studied the effect of PC combined with PEP on pain and interference by pain with daily functioning in comparison to st and ard care ( SC ) . Patients were r and omly assigned to SC ( n = 37 ) or PC‐PEP ( n = 35 ) . PEP consisted of patient‐tailored pain education and weekly monitoring of pain and side effects . We measured overall reduction in pain intensity and daily interference over an 8‐week period as well as adequacy of pain treatment and adherence . The overall reduction in pain intensity and daily interference was significantly greater after r and omization to PC‐PEP than to SC ( average pain 31 % vs 20 % , P = .03 ; current pain 30 % vs 16 % , P = .016 ; interference 20 % vs 2.5 % , P = .01 ) . Adequacy of pain management did not differ between the groups . Patients were more adherent to analgesics after r and omization to PC‐PEP than to SC ( P = .03 ) . In conclusion , PC‐PEP improves pain , daily interference , and patient adherence in oncology out patients |
12,498 | 25,192,584 | The evidence of this review indicates that monetary incentives offered to customers for a short-term look promising in increasing purchase of healthier food options when the intervention is applied by itself in stores or supermarkets .
There was a lack of good quality studies addressing all other types of relevant point-of-sale interventions examining change in purchase and /or intake of healthier food options .
Conclusions A range of intervention types have been used at point-of-sale to encourage healthy purchasing and /or intake of healthier food options and to improve health outcomes . | Background Point-of-sale is a potentially important opportunity to promote healthy eating through nutrition education and environment modification .
The aim of this review was to describe and review the evidence of effectiveness of various types of interventions that have been used at point-of-sale to encourage purchase and /or eating of healthier food and to improve health outcomes , and the extent to which effectiveness was related to intensity , duration and intervention setting . | OBJECTIVE This study tested the efficacy of a multicomponent supermarket point-of-purchase intervention featuring in-person nutrition education on the nutrient composition of food purchases . DESIGN The design was a r and omized trial comparing the intervention with usual care ( no treatment ) . SETTING AND PARTICIPANTS A supermarket in a socioeconomically diverse region of Phoenix , AZ . One hundred fifty-three adult shoppers were recruited onsite . INTERVENTION The intervention consisted of brief shopping education by a nutrition educator and an explanation and promotion of a supermarket point-of-purchase healthful shopping program that included posted shelf signs identifying healthful foods , sample shopping lists , tips , and signage . MAIN OUTCOME MEASURES Outcomes included purchases of total , saturated , and trans fat ( grams/1,000 kcal ) , and fruits , vegetables , and dark-green/yellow vegetables ( servings/1,000 kcal ) derived through nutritional analysis of participant shopping baskets . ANALYSIS Analysis of covariance compared the intervention and control groups on food purchasing patterns while adjusting for household income . RESULTS The intervention result ed in greater purchasing of fruit and dark-green/yellow vegetables . No other group differences were observed . CONCLUSIONS AND IMPLICATION S Long-term evaluations of supermarket interventions should be conducted to improve the evidence base and to determine the potential for influence on food choices associated with decreased chronic disease incidence This study examined the direct and mediated impact of a self-administered , computer-based intervention on nutrition behavior , self-efficacy , and outcome expectations among supermarket food shoppers . The intervention , housed in kiosks in supermarkets and based on social cognitive theory , used tailored information and self-regulation strategies delivered in 15 brief weekly segments . The study sample ( N = 277 ) , stratified and r and omly assigned to treatment or control , was 96 % female , was 92 % White , had a median annual income of about $ 35,000 , and had a mean education of 14.78 ±2.11 years . About 12 % of the sample reported incomes of $ 20,000 or less , and about 20 % reported 12 years or fewer of education . Analysis of covariance immediately after intervention and at a 4- to 6-month follow-up found that treatment led to improved levels of fat , fiber , and fruits and vegetables . Treatment also led to higher levels of nutrition-related self-efficacy , physical outcome expectations , and social outcome expectations . Logistic regression analysis determined that the treatment group was more likely than the control group to attain goals for fat , fiber , and fruits and vegetables at posttest and to attain goals for fat at follow-up . Latent variable structural equation analysis revealed self-efficacy and physical outcome expectations mediated treatment effects on nutrition . In addition , physical outcome expectations mediated the effect of self-efficacy on nutrition outcomes . Implication s for future computer-based health promotion interventions are discussed OBJECTIVES This study examined the effects of pricing and promotion strategies on purchases of low-fat snacks from vending machines . METHODS Low-fat snacks were added to 55 vending machines in a convenience sample of 12 secondary schools and 12 worksites . Four pricing levels ( equal price , 10 % reduction , 25 % reduction , 50 % reduction ) and 3 promotional conditions ( none , low-fat label , low-fat label plus promotional sign ) were crossed in a Latin square design . Sales of low-fat vending snacks were measured continuously for the 12-month intervention . RESULTS Price reductions of 10 % , 25 % , and 50 % on low-fat snacks were associated with significant increases in low-fat snack sales ; percentages of low-fat snack sales increased by 9 % , 39 % , and 93 % , respectively . Promotional signage was independently but weakly associated with increases in low-fat snack sales . Average profits per machine were not affected by the vending interventions . CONCLUSIONS Reducing relative prices on low-fat snacks was effective in promoting lower-fat snack purchases from vending machines in both adult and adolescent population BACKGROUND Many question whether mass media , in the absence of other programming , can produce significant and sustained behavior change . METHODS The 1 % Or Less campaign in Wheeling , West Virginia ( population 35,000 ) , used paid advertising and public relations to encourage members of one community to switch from whole or 2 % milk ( high-fat milk ) to 1 % or fat-free milk ( low-fat milk ) . The study used a quasi-experimental research design with one intervention city and one comparison city . The effectiveness of the campaign was evaluated by collecting milk sales data from supermarkets and conducting pre- and post-intervention telephone surveys in intervention and comparison cities . RESULTS In the intervention city , low-fat milk sales increased from 29 % of overall milk sales before the campaign to 46 % of sales in the month following the campaign . The increase was maintained at the 6-month follow up . According to the telephone surveys , 34.1 % of high-fat-milk drinkers reported switching to low-fat milk in the intervention community compared with 3.6 % in the comparison community ( z = 13.1 , P < 0.0001 ) . CONCLUSIONS A media-only approach was sufficient to encourage a significant proportion of the people in one community to alter the dietary habit targeted by the intervention Objectives : The supermarket industry now services many customers through online food shopping over the Internet . The Internet shopping process offers a novel opportunity for the modification of dietary patterns . The aim of this study was to evaluate the effects on consumers ' purchases of saturated fat of a fully automated computerised system that provided real-time advice tailored to the consumers ' specific purchases recommending foods lower in saturated fat . Design : This study was a blinded , r and omised controlled trial . Setting : The study was conducted in Sydney , New South Wales , Australia . Participants : The participants were consumers using a commercial online Internet shopping site between February and June 2004 . Interventions : Individuals assigned to intervention received fully automated advice that recommended specific switches from selected products higher in saturated fat to alternate similar products lower in saturated fat . Participants assigned to control received general non-specific advice about how to eat a diet lower in saturated fat . Outcome Measures : The outcome measure was the difference in saturated fat ( grams per 100 g of food ) in shopping baskets between the intervention and control groups . Results : There were 497 r and omised participants , mean age 40 y , each shopping for an average of about three people . The amount of saturated fat in the foods purchased by the intervention group was 0.66 % lower ( 95 % confidence interval 0.48–0.84 , p < 0.001 ) than in the control group . The effects of the intervention were sustained over consecutive shopping episodes , and there was no difference in the average cost of the food bought by each group . Conclusions : Fully automated , purchase-specific dietary advice offered to customers during Internet shopping can bring about changes in food purchasing habits that are likely to have significant public health implication s. Because implementation is simple to initiate and maintain , this strategy would likely be highly cost-effective BACKGROUND Reducing fruit and vegetable ( F&V ) prices is a frequently considered policy to improve dietary habits in the context of health promotion . However , evidence on the effectiveness of this intervention is limited . OBJECTIVE The objective was to examine the effects of a 50 % price discount on F&Vs or nutrition education or a combination of both on supermarket purchases . DESIGN A 6-mo r and omized controlled trial within Dutch supermarkets was conducted . Regular supermarket shoppers were r and omly assigned to 1 of 4 conditions : 50 % price discounts on F&Vs , nutrition education , 50 % price discounts plus nutrition education , or no intervention . A total of 199 participants provided baseline data ; 151 ( 76 % ) were included in the final analysis . F&V purchases were measured by using supermarket register receipts at baseline , at 1 mo after the start of the intervention , at 3 mo , at 6 mo ( end of the intervention period ) , and 3 mo after the intervention ended ( 9 mo ) . RESULTS Adjusted multilevel models showed significantly higher F&V purchases ( per household/2 wk ) as a result of the price discount ( + 3.9 kg ; 95 % CI : 1.5 , 6.3 kg ) and the discount plus education intervention ( + 5.6 kg ; 95 % CI : 3.2 , 7.9 kg ) at 6 mo compared with control . Moreover , the percentage of participants who consumed recommended amounts of F&Vs ( ≥400 g/d ) increased from 42.5 % at baseline to 61.3 % at 6 mo in both discount groups ( P = 0.03 ) . Education alone had no significant effect . CONCLUSIONS Discounting F&Vs is a promising intervention strategy because it result ed in substantially higher F&V purchases , and no adverse effects were observed . Therefore , pricing strategies form an important focus for future interventions or policy . However , the long-term effects and the ultimate health outcomes require further investigation . This trial was registered at the IS RCT N Trial Register as number IS RCT N56596945 and at the Dutch Trial Register ( http://www.trialregister.nl/trialreg/index.asp ) as number NL22568.029.08 BACKGROUND Vending machines account for food sales and revenue in schools . We examined 3 strategies for promoting the sale of lower-calorie food products from vending machines in high schools in the Netherl and s. METHODS A school-based r and omized controlled trial was conducted in 13 experimental schools and 15 control schools . Three strategies were tested within each experimental school : increasing the availability of lower-calorie products in vending machines , labeling products , and reducing the price of lower-calorie products . The experimental schools introduced the strategies in 3 consecutive phases , with phase 3 incorporating all 3 strategies . The control schools remained the same . The sales volumes from the vending machines were registered . Products were grouped into ( 1 ) extra foods containing empty calories , for example , c and ies and potato chips , ( 2 ) nutrient-rich basic foods , and ( 3 ) beverages . They were also divided into favorable , moderately unfavorable , and unfavorable products . RESULTS Total sales volumes for experimental and control schools did not differ significantly for the extra and beverage products . Proportionally , the higher availability of lower-calorie extra products in the experimental schools led to higher sales of moderately unfavorable extra products than in the control schools , and to higher sales of favorable extra products in experimental schools where students have to stay during breaks . Together , availability , labeling , and price reduction raised the proportional sales of favorable beverages . CONCLUSION Results indicate that when the availability of lower-calorie foods is increased and is also combined with labeling and reduced prices , students make healthier choices without buying more or fewer products from school vending machines . Changes to school vending machines help to create a healthy school environment BACKGROUND The greater presence of supermarkets in low-income , high-minority neighborhoods has the potential to positively affect diet quality among those at greatest risk of obesity . In-store marketing strategies that draw attention to healthier products may be effective , sustainable , and scalable for improving diet quality and health . Few controlled studies of in-store marketing strategies to promote sales of healthier items in low-income , high-minority neighborhoods have been conducted . OBJECTIVE The objective of this study was to evaluate the effects of in-store marketing strategies to promote the purchase of specific healthier items in 5 product categories : milk , ready-to-eat cereal , frozen meals , in-aisle beverages , and checkout cooler beverages . DESIGN The design was a cluster-r and omized controlled trial conducted from 2011 to 2012 . Eight urban supermarkets in low-income , high-minority neighborhoods were the unit of r and omization , intervention , and analysis . Stores were matched on the percentage of sales from government food-assistance programs and store size and r and omly assigned to an intervention or control group . The 4 intervention stores received a 6-mo , in-store marketing intervention that promoted the sales of healthier products through placement , signage , and product availability strategies . The 4 control stores received no intervention and were assessment -only controls . The main outcome measure was weekly sales of the targeted products , which was assessed on the basis of the stores ' sales data . RESULTS Intervention stores showed significantly greater sales of skim and 1 % milk , water ( in aisle and at checkout ) , and 2 of 3 types of frozen meals compared with control store sales during the same time period . No differences were found between the stores in sales of cereal , whole or 2 % milk , beverages , or diet beverages . CONCLUSIONS These data indicate that straightforward placement strategies can significantly enhance the sales of healthier items in several food and beverage categories . Such strategies show promise for significant public health effects in communities with the greatest risk of obesity Although much evidence links dietary patterns with coronary heart disease , effective and economical methods for inducing dietary change in non clinical population s are needed to influence public health . This study was design ed as a preliminary investigation of the feasibility of conducting effective nutrition education campaigns in supermarket setting s. Eight supermarkets from a supermarket chain in the Twin Cities area participated . Four were assigned to an experimental condition in which educational material s consisting of posters , recipes , and brochures were placed in the dairy section during a 6-month period . Four other stores were assigned to a control condition and received no educational material s. Shoppers in experimental and control stores completed a nutrition survey pre- and post-intervention . In addition , sales data for 25 dairy products were collected during a 10-month period . A significant increase in knowledge on the nutrition survey between pre- and posttests occurred among shoppers in all stores . There was no significant knowledge or product sales effect due to the education campaign . Study results suggest that , overall , shopper knowledge of food selection s for cardiovascular disease risk reduction is high and improving . Unfortunately , knowledge is often not reflected in food purchase patterns Objectives . We assessed the impact of a rewards-based incentive program on fruit and vegetable purchases by low-income families . Methods . We conducted a 4-phase prospect i ve cohort study with r and omized intervention and wait-listed control groups in Philadelphia , Pennsylvania , in December 2010 through October 2011 . The intervention provided a rebate of 50 % of the dollar amount spent on fresh or frozen fruit and vegetables , reduced to 25 % during a tapering phase , then eliminated . Primary outcome measures were number of servings of fruit and of vegetables purchased per week . Results . Households assigned to the intervention purchased an average of 8 ( 95 % confidence interval [ CI ] = 1.5 , 16.9 ) more servings of vegetables and 2.5 ( 95 % CI = 0.3 , 9.5 ) more servings of fruit per week than did control households . In longitudinal price-adjusted analyses , when the incentive was reduced and then discontinued , the amounts purchased were similar to baseline . Conclusions . Investigation of the financial costs and potential benefits of incentive programs to supermarkets , government agencies , and other stakeholders is needed to identify sustainable interventions This study examined the impact of an environmental intervention in the form of promotional material s and increased availability of low-fat items on vending machine sales . Ten vending machines were selected and r and omly assigned to one of three conditions : control , or one of two experimental conditions . Vending machines in the two intervention conditions received three additional low-fat selection s. Low-fat items were promoted at two levels : labels ( intervention I ) , and labels plus signs ( intervention II ) . The number of individual items sold and the total revenue generated was recorded weekly for each machine for 4 weeks . Use of promotional material s result ed in a small , but not significant , increase in the number of low-fat items sold , although machine sales were not significantly impacted by the change in product selection . Results of this study , although not statistically significant , suggest that environmental change may be a realistic means of positively influencing consumer behavior This study reports the results of one effort to help supermarket shoppers alter food purchases to make purchases ( and meals ) that are lower in fat and higher in fiber . A prototype interactive information system using instructional video programs , feedback on purchases with specific goals for change , weekly programs , and the ability to track user interactions and intended purchases was evaluated . The major dependent measure was users ' actual food purchases as derived from participants ' highly detailed supermarket receipts . After a 5- to 7-week baseline phase , participants were r and omly assigned to an experimental or control condition for the 7- to 8-week intervention phase . A follow-up phase began 5 to 8 weeks after participants completed the intervention and discontinued use of the system . The results indicated that experimental participants , when compared to control participants , decreased high fat purchases and increased high fiber purchases during intervention , with evidence for some maintenance of effect in follow-up . Plans for increasing the use and impact of the system are discussed A r and omized-control test of a multimedia nutrition intervention — the Nutrition for a Lifetime System (NLS © )— utilized supermarket receipts to examine effects of NLS treatment on the daily per person nutritional content of participants ' supermarket purchases . In regression analyses controlling for background variables , baseline purchases and trends toward increased purchasing , NLS treatment contributed to lower levels of total fat and to higher levels of total fiber and servings of fruits and vegetables at post-test . Redemption of NLS coupons contributed to greater decreases in fat and increases in servings of fruits and vegetables in users ' purchases . Implication s for future interventions promoting healthier food choices include tailoring program content and addressing broader lifestyle issues such as caloric intake and expenditure This study examined the effects of an environmental intervention promoting more non-energy-containing beverage consumption compared to sugar-sweetened soft drink consumption through vending machines in an urban college setting . Eight soft drink vending machines were r and omly selected and assigned to one of three conditions over a 9-week period : energy-content labels on non-energy-containing beverage selection panels ( intervention I ) , labels plus motivational posters ( intervention II ) , or control . The totals of all beverages sold and machine revenue were recorded at baseline ( 2 weeks ) , intervention ( 5 weeks ) , and postintervention ( 2 weeks ) periods . Use of energy-content labels and motivational posters , compared with control group , result ed in a significantly lower growth rate of sugar-sweetened beverage sales ( P<0.05 ) . Total revenue for all beverages increased during the intervention period . It is estimated that the non-energy-containing beverages combined accounted for 70.52 % of the increased revenue . Results of this study suggest that energy-content labels and motivational posters on beverage vending machines may be an effective way to influence beverage sales OBJECTIVE The present store-based intervention was design ed to promote sales of fruits and vegetables ( F&V ) to increase intake among store customers -- specifically customers of tiendas , small-to-medium-sized Latino food stores . DESIGN Four tiendas were r and omized to a 2-month environmental change intervention or a delayed treatment control condition . Employees and managers were trained to promote F&V sales , including how to implement a food marketing campaign and installing store equipment to promote fresh fruits and vegetables . The primary outcome was self-reported daily intake of F&V among a convenience sample of customers ( at least forty per store ) collected at baseline prior to r and omization and then 4 months later . In addition , changes in availability of F&V in the tiendas , using unobtrusive observational methods , provided evidence of intervention fidelity . SETTING Tiendas in central North Carolina . SUBJECTS Participants included 179 customers who were recent immigrants from Mexico and Central America . RESULTS A group-by-time interaction approached significance on daily servings of F&V ; intervention customers reported an increase in F&V intake over time and as a function of the intervention ( P < or = 0.06 ) . Unexpectedly , self-efficacy for consuming more fruits ( P < or = 0.01 ) and more vegetables ( P < or = 0.06 ) decreased . In our store-level analyses , a group-by-time interaction was observed for availability of fresh and canned vegetables ; the intervention increased availability of vegetables but not fruit . CONCLUSIONS Environmental change strategies to promote healthy eating are needed given the rates of obesity and diabetes in the Latino population . A store-based intervention was moderately effective at increasing customers ’ reported F&V intake . Such strategies can have a public health impact on underserved population BACKGROUND Theory-based approaches to public health interventions are useful for design ing , implementing , and evaluating research . This paper describes and presents data to support the theoretical force behind the " 1 % or less " nutrition intervention studies . METHODS Using the Theory of Reasoned Action ( TRA ) , high-fat ( whole and 2 % ) milk users were targeted . Supermarket milk sale data were collected , and r and omly selected intervention and comparison community residents were surveyed via telephone to assess milk use . TRA constructs were used in the surveys that were conducted immediately before and after a 6-week mass media campaign . Campaign messages were aim ed at changing behavioral rather than normative beliefs . RESULTS We found significant and predicted changes in intervention participants on intention , attitude , and behavioral beliefs , but not subjective norm outcomes . A path model showed support that TRA variables mediated significant changes in self-reported milk use . CONCLUSIONS The analysis further vali date s the TRAs and supports a template using both the Principle of Compatibility and TRA to aid development and implementation of messages for effective behavior change field interventions Purpose . The purpose of this study was to evaluate whether a supermarket point-of-purchase intervention could increase shoppers ' consumption of fruits and vegetables . Methods . Eight supermarkets in rural Iowa were r and omized to receive either an 8-month intervention or no intervention . The intervention consisted of ( 1 ) one-page supermarket flyers that identified fruits and vegetables on sale , gave recipes and menu ideas for using sale foods , and gave a store coupon worth 50 cents toward the purchase of any fruit or vegetable ; ( 2 ) store signage to identify fruits and vegetables featured on the flyer ; and ( 3 ) consciousness raising activities such as food demonstrations and nutrition related signage . Evaluation was based on exit interviews and take-home surveys , completed by r and om sample s of 120 shoppers from each store at baseline and approximately 1-year post r and omization . Results . At follow-up , 42.9 % of intervention store shoppers and 6.5 % of control shoppers recalled seeing the intervention flyer . Thirty-six percent of intervention shoppers had used a 50-cent coupon and 18 % had used a recipe . Approximately 70 % of all shoppers had purchased fruits or vegetables on the day they were interviewed , which did not differ between intervention and control stores . Compared to change in control shoppers , there was a borderline statistically significant 8.4 percentage point increase ( p < .07 ) in the percentage of intervention store shoppers in the action or maintenance stages of dietary change , but there was no corresponding increase in fruit and vegetable consumption . Discussion . Studies to test point-of-purchase interventions are difficult to design , implement , and evaluate . More powerful interventions are probably necessary to induce shoppers to purchase and consume more fruits and vegetables Obesity and other diet-related chronic diseases are more prevalent in low-income urban areas , which commonly have limited access to healthy foods . The authors implemented an intervention trial in nine food stores , including two supermarkets and seven corner stores , in a low-income , predominantly African American area of Baltimore City , with a comparison group of eight stores in another low-income area of the city . The intervention ( Baltimore Healthy Stores ; BHS ) included an environmental component to increase stocks of more nutritious foods and provided point-of-purchase promotions including signage for healthy choices and interactive nutrition education sessions . Using pre- and post assessment s , the authors evaluated the impact of the program on 84 respondents sample d from the intervention and comparison areas . Exposure to intervention material s was modest in the intervention area , and overall healthy food purchasing scores , food knowledge , and self-efficacy did not show significant improvements associated with intervention status . However , based on adjusted multivariate regression results , the BHS program had a positive impact on healthfulness of food preparation methods and showed a trend toward improved intentions to make healthy food choices . Respondents in the intervention areas were significantly more likely to report purchasing promoted foods because of the presence of a BHS shelf label . This is the first food store intervention trial in low-income urban communities to show positive impacts at the consumer level BACKGROUND Traditional methods to improve population diets have largely relied on individual responsibility , but there is growing interest in structural interventions such as pricing policies . OBJECTIVE The aim was to evaluate the effect of price discounts and tailored nutrition education on supermarket food and nutrient purchases . DESIGN A 2 x 2 factorial r and omized controlled trial was conducted in 8 New Zeal and supermarkets . A total of 1104 shoppers were r and omly assigned to 1 of the following 4 interventions that were delivered over 6 mo : price discounts ( 12.5 % ) on healthier foods , tailored nutrition education , discounts plus education , or control ( no intervention ) . The primary outcome was change in saturated fat purchased at 6 mo . Secondary outcomes were changes in other nutrients and foods purchased at 6 and 12 mo . Outcomes were assessed by using electronic scanner sales data . RESULTS At 6 mo , the difference in saturated fat purchased for price discounts on healthier foods compared with that purchased for no discount on healthier foods was -0.02 % ( 95 % CI : -0.40 % , 0.36 % ; P = 0.91 ) . The corresponding difference for tailored nutrition education compared with that for no education was -0.09 % ( 95 % CI : -0.47 % , 0.30 % ; P = 0.66 ) . However , those subjects who were r and omly assigned to receive price discounts bought significantly more predefined healthier foods at 6 mo ( 11 % more ; mean difference : 0.79 kg/wk ; 95 % CI : 0.43 , 1.16 ; P < 0.001 ) and 12 mo ( 5 % more ; mean difference : 0.38 kg/wk ; 95 % CI : 0.01 , 0.76 ; P = 0.045 ) . Education had no effect on food purchases . CONCLUSIONS Neither price discounts nor tailored nutrition education had a significant effect on nutrients purchased . However , the significant and sustained effect of discounts on food purchases suggests that pricing strategies hold promise as a means to improve population diets |
12,499 | 17,054,141 | One study comparing sclerotherapy to GCS in pregnancy found that sclerotherapy improved symptoms and cosmetic appearance .
Three studies comparing sodium tetradecyl sulphate ( STD ) to alternative sclerosants found no significant differences in outcome or complication rates ; another study found that sclerotherapy with STD led to improved cosmetic appearance compared with polidocanol , although there was no difference in symptoms .
The degree and duration of elastic compression had no significant effect on varicose vein recurrence rates , cosmetic appearance or symptomatic improvement .
AUTHORS ' CONCLUSIONS Evidence from RCTs suggests that the choice of sclerosant , dose , formulation ( foam versus liquid ) , local pressure dressing , degree and length of compression have no significant effect on the efficacy of sclerotherapy for varicose veins . | BACKGROUND Injection sclerotherapy is widely used for superficial varicose veins .
The treatment aims to obliterate the lumen of varicose veins or thread veins .
There is limited evidence regarding its efficacy .
OBJECTIVES To determine whether sclerotherapy is effective in improving symptoms and cosmetic appearance and has an acceptable complication rate ; to define rates of symptomatic or cosmetic varicose vein recurrence following sclerotherapy . | Three techniques for treatment of chronic venous incompetence on an out patients basis were compared in a r and omised study . One hundred thirty eight limbs ( 107 patients ) with superficial venous incompetence were r and omly treated with the dentist 's technique ( DT ) [ Group A , 44 limbs ] , compression sclerotherapy ( CS ) [ Group B , 45 limbs ] or the SAVAS ( section en Ambulatoire des Varices avec Sclérothérapie ) technique [ Group C , 49 limbs ] . Patients were evaluated and followed up ( every year for 4 years ) with ambulatory venous pressure ( AVP ) measurements and Quantum angiodynography ( colour duplex scanning ) . DT consisted in the section under local anesthesia of incompetent veins . CS was done injecting polidocanol 3 % with compression applied for 4 weeks . The SAVAS was done with a combination of DT and CS with section of the incompetent veins under local anesthesia and retro grade injection in the distal vein of polidocanol 3 % . With this type of injection only incompetent veins were perfused . After 4 years there was a significantly lower refilling time ( RT ) with AVP in the SAVAS group ( 21 sec ) . RT was 13 sec in group B and 16 in A. The number of significantly incompetent residual veins was in average 0.5 in the SAVAS group , significantly lower than in the other two groups . Also the average cost per treated limb was significantly lower in the SAVAS group ( 917 francs in comparison with 1100 in group A and 1211 in group B ) . In conclusion considering the four year follow up , the SAVAS technique is a more effective treatment of superficial venous incompetence , its hemodynamic value is superior to sclerotherapy alone and its costs are lower The influence of compression sclerotherapy upon hemostasis activation was investigated in 41 consecutive patients with lower extremity varices by serial measurement of thrombin-antithrombin III complexes ( TAT ) , D-dimer , fibrinogen and C-reactive protein ( CRP ) . Blood sampling was carried out before operation and on the 7th and 28th post-operative day in patients r and omly assigned to either the control group ( n = 18 ) , in which high ligation of sapheno-femoral junction and local excision of varices were performed , or the sclerotherapy group ( n = 23 ) in which the comparable surgical intervention and compression sclerotherapy using hypertonic saline were performed simultaneously . In both groups , the TAT , D-dimer and fibrinogen concentrations at day 7 were significantly elevated compared to the value before operation while CRP showed no significant change during the observation period . In the sclerotherapy group , higher incidence of superficial thrombosis was observed and the TAT concentration at day 7 was significantly higher than that in the control group ( p < 0.01 ) , and the TAT at day 28 was still significantly elevated compared to the pre-operative level ( p < 0.05 ) . However , no relationship between TAT and D-dimer concentrations and the extent of superficial thrombosis was observed . We conclude that compression sclerotherapy for lower extremity varices causes latent activation of coagulation system and can be a risk factor for venous thromboembolism 169 legs with primary varicose veins suitable for sclerotherapy were entered into the trial . At the time of injection they were r and omly allocated to be b and aged for three or six weeks ; patients allocated to the six-week group had their legs reb and aged after the first three week . Patients were subsequently assessed blind at three months and thereafter at yearly intervals PURPOSE The efficacy of sclerosing agents for the treatment of telangiectasias and reticular veins is well established . The injection of these agents is often associated with pain , and it is not uncommon for sclerotherapists to include lidocaine with the sclerosants in an attempt to reduce the pain associated with treatment . However , there are concerns that this may reduce the overall efficacy of the treatment because of dilution of the sclerosant . Patient comfort and overall outcome associated with treatment using HS with lidocaine ( LIDO ) versus that using HS alone was compared . METHODS Forty-two patients were prospect ively entered into the study and r and omized blindly to sclerotherapy with 23.4 % HS or 19 % LIDO . Study subjects and treating physicians were blinded to the injection solution used . Injection sites were chosen for veins ranging in size from 0.1 to 3 mm . Photographs of the area to be treated were taken , and the patients rated their pain . They were then observed at regular intervals for four months , and clinical data was collected . Thirty-five subjects completed the full follow-up period , and photographs of the injected area were taken again . Three investigators blinded to the treatment assignment then evaluated the photographs and scored the treatment efficacy according to a st and ardized system . RESULTS In the HS group , 61.9 % ( 13 of 21 ) patients rated their pain as none or mild , whereas 90.5 % ( 19 of 21 ) of patients in the LIDO group had no or mild discomfort . This difference is significant , with a P value of.034 . There was no difference in the overall efficacy of treatment between the two groups . The groups had similar rates of vein thrombosis and skin necrosis . CONCLUSION Although lidocaine is often used with sclerosing agents , there are no previous reports in the literature to evaluate its effectiveness in reducing the pain experienced by the patient . In this study , patients receiving LIDO experienced significantly less discomfort at the time of injection than patients who received HS alone . There were no differences in the effectiveness of treatment or in the incidence of complications between the two groups Following sclerotherapy of varicose veins , 158 limbs of 154 patients were r and omized to be b and aged with either crepe or Coban for 6 weeks each , or with Coban for 3 days only . Objective assessment of vein eradication and subjective evaluation of symptoms 3 months after completion of treatment showed no clear differences between these regimens . Significantly more discomfort was experienced with Coban than crepe when used for 6 weeks . It is suggested that , following sclerotherapy , 3 days is an adequate period of b and aging when using Coban . Such a policy would considerably reduce the inconvenience to patients during treatment Since thrombotic complications , such as superficial thrombophlebitis and subsequent skin pigmentation , are common after sclerotherapy , we conducted a study to evaluate whether combining sclerotherapy with ligation of varicose veins minimizes complications and what timing for sclerotherapy would be most beneficial-accompanying surgery or several weeks postsurgery . Surgical intervention and compression sclerotherapy were performed consecutively on 111 limbs ( group A ) , and sclerotherapy was performed 28 days after surgical intervention on 87 limbs ( group B ) . The volume of sclerosant used and the frequency of complications ( thrombus formation and pigmentation ) were analyzed . Plasma levels of thrombin-antithrombin III complex ( TAT ) and D-dimer ( DD ) , as markers for activation of coagulation , were compared . In group A , the total volume of sclerosant used in patients with complications was significantly higher than that in patients without complications . The frequency of thrombus formation and of pigmentation was significantly lower ( p < 0.01 ) in group B ( 10 % and 18 % , respectively ) than in group A ( 21 % and 37 % , respectively ) . The plasma levels of TAT 7 days after treatment were significantly lower in group B ( 3.4 + /- 1.2 mg/L ) than in group A ( 4.9 + /- 1.1 mg/L ) . Performing compression sclerotherapy 28 days after surgical intervention is effective for reducing complications and a good alternative for patients with an underlying hypercoagulable state BACKGROUND Sclerotherapy has traditionally been considered the gold st and ard of treatment for leg veins , but patient fear of multiple needle injections and side effects of treatment have fueled investigation into other treatment alternatives . As a result , vascular-specific laser and light sources have been developed in an effort to treat these vessels with minimal morbidity and improved efficacy . OBJECTIVE To compare the clinical efficacy of leg telangiectasia treatment with sodium tetradecyl sulfate sclerotherapy to long-pulsed 1064 nm Nd : YAG laser irradiation . METHODS A series of 20 patients with size-matched superficial telangiectases of the lower extremities were r and omly assigned to receive two consecutive monthly treatments with injectable sodium tetradecyl sulfate on one leg and long-pulsed 1064 nm Nd : YAG laser irradiation on the other . Patients were evaluated by two masked assessors at each treatment visit and at 1 and 3 months after treatment to assess clinical improvement within matched sites . RESULTS Leg telangiectases responded best to sclerotherapy in fewer treatment sessions than to long-pulsed 1064 nm Nd : YAG laser irradiation . The incidence of adverse sequelae was minimal and equivocal in both treatment groups . CONCLUSION Despite recent advances in laser technology for treatment of lower extremity telangiectases , sclerotherapy continues to offer superior clinical effect in the majority of cases . Laser leg vein treatment appears to be most beneficial in patients with telangiectatic matting , needle phobia , or sclerosant allergy BACKGROUND . Thirteen patients were treated with either sodium tetradecyl sulfate ( STS ) or glycerin to compare the efficacy and adverse sequelae of each agent . OBJECTIVE . To determine the relative safety and efficacy of two sclerosant solutions . METHODS . Each patient 's leg veins that were from 0.2 to 0.4 mm in diameter and that did not have incompetence from the saphenofemoral junction and whose feeding reticular veins had been already treated in a prior sclerotherapy session were r and omly treated with either 0.25 % STS or 72 % glycerin solution . Patients were evaluated from 2 to 6 months postsclerotherapy for overall clinical improvement and incidence of adverse sequelae . RESULTS . Glycerin was comparable to STS in discomfort of injection but demonstrated a significant decrease in bruising , swelling , and postprocedural hyperpigmentation . Glycerin also demonstrated a better , more rapid clearance of treated telangiectasias . Conclusions . Seventy‐two percent glycerin is a safe and effective sclerosant with fewer side effects and more rapid clearance of telangiectatic leg veins than STS BACKGROUND Although no r and omized controlled trial has assessed the effects of either compression sclerotherapy or ambulatory phlebectomy , both techniques are used to treat varicose veins worldwide . We performed a r and omized controlled trial to compare recurrence rates of varicose veins and complications after compression sclerotherapy and ambulatory phlebectomy . METHODS From September 1996 to October 1998 , we r and omly allocated 49 legs to compression sclerotherapy and 49 legs to ambulatory phlebectomy . Our primary outcome parameters were as follows : recurrence rates at 1 and 2 years and complications related to therapy . Eighty-two patients were included , of whom 16 were included with both of their legs . The number of treated legs was therefore 98 , but two patients were lost to follow-up . RESULTS One year recurrence amounted to 1 out of 48 for phlebectomy and 12 out of 48 for compression sclerotherapy ( P < 0.001 ) ; at 2 years , six additional recurrences were found , but then solely for compression sclerotherapy ( P < 0.001 ) . Significant differences in complications occurring more in phlebectomy than in compression sclerotherapy therapy were blisters , teleangiectatic matting , scar formation , and bruising from b and aging . CONCLUSION Our results show that ambulatory phlebectomy is an effective therapy for varicose veins of the leg . Recurrence rates are significantly lower than for compression sclerotherapy therapy . If varicose veins persist 4 weeks after compression sclerotherapy , it can be argued that to reduce the risk of future recurrence ambulatory phlebectomy should be considered as the better treatment option The study was planned to evaluate efficacy and costs of endovascular sclerotherapy ( ES ) in comparison with surgery and surgery associated with sclerotherapy in a prospect i ve ( 10-year follow-up ) , good- clinical - practice study . Patients with varicose veins and pure , superficial venous incompetence were included . Of the patients r and omized into the three groups 39 ( group A ) were treated with ES , 40 ( B ) with surgery + sclerotherapy , and 42 with surgery only ( C ) . Surgery consisted of ligation of the SFJ ( saphenofemoral junction ) and of incompetent veins detected with color duplex . Of the preselected 150 patients , 121 subjects entered the study ; 96 completed the 10-year follow-up ( mean age 52.6 ±6 years ; 51 men , 45 women ) . Dropouts were due to nonmedical problems . At 10 years no incompetence was observed in subjects treated with SPJ ligation ( B and C ) . In the ES group 18.8 % of the SFJs were patent and incompetent and in 43.8 % of limbs the distal ( below-knee ) venous system was still incompetent [ 16.1 % in the surgery + scle rotherapy group ( p < 0.05 ) and 36 % in the group treated with surgery only ( p < 0.05 vs B and 0.05 vs A ) ] . Color duplex of the long saphenous vein indicated atrophy or obstruc tion of a segment ( average 6.7 cm ) after SFJ ligation ( 4.2 cm after ES ) . The cost of ES was 68 % of surgery while the cost of surgery and sclerotherapy was 122 % of surgery only . Endovascular sclerotherapy is an effective , cheaper treatment option , but surgery after 10 years is superior There is uncertainty regarding the most satisfactory technique of lower limb compression following sclerotherapy for varicose veins . We have compared a st and ard b and aging technique with a high pressure compression stocking in a r and omised trial . Efficacy was judged on the success of injections , complications of the treatment and patient satisfaction . In the stockinged legs 144 of 156 injections were successful , compared with 117 of 147 in the b and aged group ( P less than 0.001 ) ( Chi squared ) . The incidence of superficial thrombophlebitis was also reduced in the stocking group . In addition , the stocking technique costs less in material s than conventional b and aging . We would recommend compression stockings for evaluation in sclerotherapy of varicose veins OBJECTIVE The objective of this study was to investigate the efficacy of sclerotherapy for varicose veins in a r and omized blinded study . METHODS Twenty-five patients with varicose veins ( C2 - 4 , EP , ASP , PR ) were included . Fourteen subjects received polidocanol ( Aethoxysklerol ) and 11 patients received normal saline injections . Compression was applied for 1 week . One , 4 , and 12 weeks later controls were performed using duplex ultrasonography . The quotient of venous by arterial volume flow was used as quantitative hemodynamic pattern . Patients and the examiner were unaware of which liquid had been injected . RESULTS In comparison to group 2 , 76.8 % of the veins treated with polidocanol were completely occluded ( p < 0.0001 ) . In group 1 the venoarterial flow index decreased from 1.45±0.66 to 1.06±0.2 ( p = 0.05 ) . In 11 occluded veins of 14 ( group 1 ) , the venoarterial flow index decreased from 1.5±0.07 to 0.98±0.12 ( p < 0.05 ) , which is a level found in competent veins . In group 2 , the venoarterial flow index remained stable increased . CONCLUSIONS Injection sclerotherapy using polidocanol ( Aethoxysklerol ) is efficient to obliterate varicose veins and to improve venous hemodynamics OBJECTIVE To compare the long-term value of different forms of treatment for primary varicose veins with saphenous vein insufficiency . EXPERIMENTAL DESIGN A prospect i ve , partially r and omized study with 5-year follow-up . SETTING Ambulatory day-case care . PATIENTS AND INTERVENTIONS The study includes 211 patients ( 214 lower limbs ) , who received compression sclerotherapy ( CST ; n = 78 ) , radical operation ( OP ; n = 74 ) or CST combined with high tie under local anesthesia ( HT + CST ; n = 63 ) . MEASURES The patient 's subjective opinion , objective finding by the surgeon and functional ( foot-volumetric ) assessment were obtained just after treatment and 6 months , 1 , 3 and 5 years later . RESULTS Subjectively the result started to deteriorate in both the CST and HT + CST groups after one year . The patient satisfaction was greatest in the OP group throughout the study period . Objective ly the CST group cure rate fell markedly after 6 months and at 5 year follow-up the failure rate reached 51 % , while the OP group still had a high rate of cured ( 60 % ) and improved ( 35 % ) patients . The HT + CST treatment seemed to hold well for three years followed by increasing failure rate with only 16 % objective ly cured after 5 years . The foot-volumetric parameters expelled volume (= calf pump function ) and refilling flow ratio (= venous reflux ) increased 51 - 79 % respectively decreased 8 - 29 % post-treatment in all groups . After 5 years these parameters had returned to pre-treatment levels in the CST and HT + CST groups , while the OP group was still significantly improved . CONCLUSIONS Radical surgery is superior to compression sclerotherapy alone or in combination with high tie in the treatment of varicose veins with saphenous vein incompetence . The foot-volumetric assessment correlated well with and supported objective findings as a whole but could not replace the clinical examination of each individual patient BACKGROUND One hundred twenty-nine patients were treated with either polidocanol ( POL ) or sodium tetradecyl sulfate ( STS ) to compare the efficacy and adverse sequelae of each agent . OBJECTIVE To determine the safety and efficacy of two sclerosing solutions . METHODS Each patient 's leg veins that did not have incompetence from the saphenofemoral junction ( SFJ ) were divided into three categories by size ( < 1 mm , 1–3 mm , 3–6 mm ) . Each leg was r and omly treated with either 0.25 % , 0.5 % , or 1.5 % of STS or 0.5 % , 1.0 % , or 3 % of POL respective of size . An independent , three-panel , blindly r and omized photographic examination was obtained pretreatment and at 4 and 16 weeks . Patient satisfaction index and overall clinical improvement assessment were also obtained . RESULTS All patients had an average of 70 % improvement and were 70–72 % satisfied in all vein categories treated with either solution . There was no significant difference in adverse effects between each group except for a decrease in ulcerations and swelling in the POL group . CONCLUSION Both STS and POL are safe and effective sclerosing solutions for varicose and telangiectatic leg veins BACKGROUND Foamed sclerosing agents have been used with enthusiasm by phlebologists for more than 5 decades . Any type of varicose veins can and has been treated with this technique . Numerous publications have stressed the advantages of foamed sclerosing agents on the basis of empiric and experimental criteria and have described various individual techniques to prepare foams . Until now , however , no comparative study for the treatment of large varicose veins with foam or liquid exists . OBJECTIVE The purpose of this first r and omized , prospect i ve , multicenter trial was to study the elimination of reflux , the rate of recanalization , and possible side effects of foam sclerotherapy ( FS ) compared with conventional liquid sclerotherapy for the greater saphenous vein ( GSV ) . METHODS Eighty-eight patients were r and omized into two groups : One group was treated with sclerosing foam ( 45 patients ) and the other with sclerosing liquid ( 43 cases ) . Sclerotherapy was performed with direct puncture of the vessel under duplex guidance . The reference sclerosing agent was polidocanol in a 3 % solution . The foam was prepared using the Double Syringe System ( DSS ) method . Only one injection of 2.0 or 2.5 mL liquid or foam was allowed , depending on the diameter of the GSV . Results were assessed according to the protocol . RESULTS Follow-up after 3 weeks showed 84 % elimination of reflux in the GSV with DSS foam versus 40 % with liquid sclerosant ( P < 0.01 ) . At 6 months , six recanalizations were found in the liquid group versus two in the foam group . After 1 year , no additional recanalization was observed with either foam or liquid . Longer term studies are underway . Side effects did not differ between both groups . CONCLUSION The efficacy of sclerosing foam ( DSS ) compared with sclerosing liquid in therapy of the GSV is superior , a finding that had already gained empirical recognition but for which there has not been any clinical evidence to date OBJECTIVE Postsclerotherapy pigmentation occurs in nearly 30 % of patients . Hemosiderin , from degradation of the venous thrombus , is the possible cause . The hypothesis that early removal of the thrombus may eliminate or decrease the incidence of pigmentation has not been proved or documented . The objective of this study was to investigate the effects of early microthrombectomy on incidence of postsclerotherapy pigmentation . MATERIAL AND METHODS This multicenter , r and omized , controlled study involved 101 patients with varicose veins ( 100 women , 1 man ; mean age , 46 years [ range , 25 - 68 years ] ) . Patients were divided into two groups , with veins 1 mm or less in diameter ( group 1 , n = 50 ) or veins 3 mm or less in diameter ( group 2 , n = 51 ) . Group 1 was treated with Sotradecol ( STD ) 0.25 % , and group 2 with STD 0.50 % . In each patient , an area of varicosities was selected and divided into halves . One half was r and omized to microthrombectomy and the other half served as control . Microthrombectomy was performed 1 to 3 weeks after treatment in the r and omized half . St and ard photographs were obtained before and 16 weeks after treatment , and were evaluated by three independent review ers who were blinded to treatment assignments . Each review er received an identical set of pretreatment and posttreatment 10 x 15-cm color photographs of the study area , and completed a scoring sheet . Average of the scores was used to evaluate primary ( pigmentation ) and secondary ( overall clinical improvement ) end points . The paired t test and chi-square test were used for statistical analysis . RESULTS In group 1 , microthrombectomized areas had statistically significant less pigmentation ( P = .0047 ) and better overall clinical improvement scores ( P = .0002 ) compared with the control side . In group 2 there was no significant difference between the two areas , but patients reported significant relief of pain and inflammation associated with postsclerotherapy thrombophlebitis . CONCLUSION In veins 1 mm or smaller , microthrombectomy reduced pigmentation and improved overall clinical results . In veins 3 mm or smaller , statistical significance was not achieved , but thrombectomy result ed in faster resolution of the postsclerotherapy pain and inflammation . On the basis of these results , microthrombectomy after sclerotherapy is recommended The study compared , by a prospect i ve , r and omized method , 6 treatment options : A : Sclero therapy ; B : High-dose sclerotherapy ; C : Multiple ligations ; D : Stab avulsion ; E : Foam-sclero therapy ; F : Surgery ( ligation ) followed by sclerotherapy . Results were analyzed 10 years after inclusion and initial treatment . Endpoints of the study were variations in ambulatory venous pressure ( AVP ) , refilling time ( RT ) , presence of duplex-reflux , and number of recurrent or new incompetent venous sites . The number of patients , limbs , and treated venous segments were comparable in the 6 treatment groups , also comparable for age and sex distribution . The occur rence of new varicose veins at 5 years varied from 34 % for group F ( surgery + sclero ) and ligation ( C ) to 44 % for the foam + sclero group ( E ) and 48 % for group A ( dose 1 sclero ) . At 10 years the occurrence of new veins varied from 37 % in F to 56 % in A. At inclusion AVP was comparable in the different groups . At 10 years the decrease in AVP and the increase in RT ( indicating decrease in reflux ) , was generally comparable in the different groups . Also at 10 years the number of new points of major incompetence was comparable in all treatment groups . These results indicate that , when correctly performed , all treatments may be similarly effective . " St and ard , " low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain , in selected subjects , results comparable to surgery Graduated compression stockings are used in both surgical and non-surgical treatment of varicose veins . In a trial of high versus low compression stockings ( 40 mmHg vs 15 mmHg at ankle ) after varicose vein surgery , both were equally effective in controlling bruising and thrombophlebitis , but low compression stockings proved to be more comfortable . In a further trial after sclerotherapy , high compression stockings alone produced comparable results to Elastocrepe b and ages with stockings . It is concluded that after varicose vein surgery low compression stockings provide adequate support for the leg and that after sclerotherapy , b and aging is not required if a high compression stocking is used Abstract Objective : To define the relations between age , sex , lower limb symptoms , and the presence of trunk varicose veins on clinical examination . Design : Cross sectional population study . Setting : 12 general practice s with catchment areas geographically and socioeconomically distributed throughout Edinburgh . Participants : An age stratified r and om sample of 1566 people ( 699 men and 867 women ) aged 18 - 64 selected from the computerised age-sex registers of participating practice s. Main outcome measures : Self administered question naire on the presence of lower limb symptoms and physical examination to determine the presence and severity of varicose veins . Results : Women were significantly more likely than men to report lower limb symptoms such as heaviness or tension , swelling , aching , restless legs , cramps , and itching . The prevalence of symptoms tended to increase with age in both sexes . In men , only itching was significantly related to the presence and severity of trunk varices ( linear test for trend , P=0.011 ) . In women there was a significant relation between trunk varices and the symptoms of heaviness or tension ( P 0.001 ) , aching ( P 0.001 ) , and itching ( P 0.005 ) . However , the level of agreement between the presence of symptoms and trunk varices was too low to be of clinical value , especially in men . Conclusions : Even in the presence of trunk varices , most lower limb symptoms probably have a non-venous cause . Surgical extirpation of trunk varices is unlikely to ameliorate such symptoms in most patients In a controlled clinical investigation 516 patients with previously untreated saphenous varices were divided into three treatment groups according to a stratified group comparative design . The patients in treatment group 1 underwent a radical operation under full anaesthesia ; the patients in group 2 were treated by means of minor operations followed by injection/compression therapy ; the patients in group 3 were treated by means of injection/compression therapy alone . The results were evaluated both objective ly and subjectively 3 months and 3 years after treatment , the follow‐up being 100 per cent and 98.1 per cent complete at those times . With regard to the period of disability among those patients with jobs outside the home ( 63.8 per cent ) , there was a statistically significant difference between the three groups , the median period of disability being 14.2 , 7.6 and 0 days respectively . In all three treatment groups the results were worse after 3 years than after 3 months , but the difference was significantly less following radical operation than after combined treatment , and significantly less following combined treatment than after injection/compression therapy alone . The patients were r and omized and treated by the author and the results of treatment were evaluated by the author and partly controlled by another investigator Ankle ulcers associated with venous disease have been traditionally treated by Unna 's compressive b and ages . However , successful healing of an ulcer with this therapeutic modality is slow and tedious . The purpose of this study is to investigate whether adjunctive sclerotherapy of large venous channels near the ulcers enhances healing . Twenty-eight patients with perimalleolar venous ulceration were entered into this study . Ulcer size ranged from 6.0 to 25 cm2 . All were examined for the presence of large venous channels adjacent to the ulcer bed . A portable continuous-wave Doppler supplemented digital examination of the area . Twenty-five out of 28 patients had easily detectable venous channels , and these were r and omized into two groups : group I , treated by weekly changes of Unna 's compressive boots ; group II , treated by weekly change of Unna 's compressive boots and sclerotherapy with 3 % sodium tetradecyl sulfate ( Sotradecol ) . All patients had the size of the ulcer measured during their weekly visits . Patients in group II took a mean of 2.1 weeks to exhibit 50 % healing and 4.3 weeks to fully heal . Conversely patients in group I took a mean of 3.2 weeks to achieve 50 % healing and 6.1 weeks to fully heal . Thus , healing was significantly faster ( p less than 0.05 ) in group II . In conclusion , the therapeutic efficiency of Unna 's compressive b and aging is significantly enhanced by the adjunctive sclerotherapy of adjacent venous channels This prospect i ve r and omized study compared the treatment of greater saphenous vein insufficiency by stripping and local avulsions of varicose veins with high ligation of the saphenofemoral junction ( crossectomy ) combined with sclerocompression therapy . Of 156 consecutive patients , 89 legs were r and omly allocated to stripping and 92 to high ligation . At follow-up of 3 months and 1 , 2 , and 3 years after treatment , clinical and Doppler ultrasound results , and complaints and cosmetic results , as judged by the patient and the surgeon , were scored . At 3 years , 69 limbs in the stripping group ( 78 % ) and 73 limbs in the ligation group ( 79 % ) were available to follow-up . The cosmetic results , both judged by the patient and the surgeon , were significantly better ( P < 0.05 ) in the stripped limbs than in the limbs with high ligation and sclerotherapy . Clinical and Doppler ultrasound evidence of reverse flow in the saphenous vein was significantly less ( P < 0.001 ) after the stripping operation . The results of treatment of isolated saphenous vein insufficiency by stripping operation , therefore , were superior to those obtained by high ligation combined with sclerotherapy AIMS To compare the short and long term results of different techniques of compression sclerotherapy . PATIENTS AND METHODS In the past 10 years the authors treated 1622 pts due to chronic venous insufficiency . There were 3 groups of patients : 1 ) Pts treated by Sigg 's technique using Aethoxysclerol , 2 ) Pts treated by Fegan 's technique with Fibrovein , and 3 ) Pts treated by Fegan 's procedure , but using a combination of both sclerosants . In all cases , the techniques of empty vein , bubble air , uninterrupted 6-week compression and forced mobilisation were used . RESULTS In the group of pats . treated by Sigg 's procedure , the average cure rate was 67.47 % after 6 months , 60.3 % after 5 years of follow-up . In Fegan 's group this rate was 83.6 % after 6 months and 78.54 % after 5 year assessment . Statistically , significant differences were found only by the disappearance of varices and reduction of pain in favour of Fegan 's technique . In the group of pts treated by Fegan 's ( Aethoxysclerol + Fibrovein ) this rate after 5 years was 86 % . The only statistically significant difference was found by the disappearance of varices in favour of Fegan 's technique using a combination of 2 detergent sclerosants . CONCLUSIONS Sclerotherapy is effective when properly executed in any length of vein no matter how dilated it has become . The recurrences are attributed more to inadequate technique than to the shortcoming of the procedure . Sclerotherapy is miniinvasive , with few complications , and can be repeated on out-patient basis . ( Tab . 1 , Ref . 22 . ) A r and omised controlled trial was carried out to compare the clinical outcome 5 years after inpatient surgery and outpatient injection/compression sclerotherapy . 91.3 % of those originally treated by injection/compression sclerotherapy and 93.9 % of those originally treated surgically were seen at follow-up . 40 % of patients treated initially by injection/compression sclerotherapy and 24.2 % of those treated surgically were given further treatment . The probability of having no further treatment is significantly greater for those treated surgically . The improved outcome after surgery increased with age , being most striking in those aged over 45 . The implication s of the 5-year follow-up findings for the long-term cost of treatment are discussed Varicose veins are a common problem , and yet there is divergent opinion as to whether surgery or sclerotherapy is the preferred method of treatment . After establishing a reliable injection technique , the method was compared with st and ard surgical procedures in a r and om trial . The results showed that after one year 82 % of unselected patients were cured by injection , but after six years the cure rate was only 7 % . The surgical result was not as good at one year , but much better than injection after six years . When the results were considered for three distinct clinical groups , the analysis showed that the best primary treatment for dilated superficial veins and for incompetent perforating veins in the lower part of the legs was injection-compression . However , surgery was much more successful and long-lasting when there was involvement of the saphenous systems with proximal incompetence Abstract A r and omised controlled trial has been carried out to compare the clinical outcome in patients treated for varicose veins by routine surgery and injection/compression sclerotherapy . 115 patients were treated with injection/ compression sclerotherapy and 100 were treated surgically . 93 % of those treated have been seen three years after treatment , by then 14 % in the surgical group and 22 % in the injection/compression group had been given further treatment ; there is no significant difference between the results of the two forms of treatment . The patients preferred injection/ compression sclerotherapy , and fewer failed to attend for this treatment than for surgery A clinical trial was carried out to compare the effectiveness of compressive sclerotherapy with that of the traditional operative procedures in the treatment of varicose veins . One hundred and ten patients were treated by compression sclerotherapy and 91 patients by operation The author reports the results of a double-blind , paired-comparison study using saline sclerosant plus or minus heparin additive . The study was design ed to eluci date the effects of increasing concentrations of hypertonic saline with regard to vessel diameter , clinical efficacy , complications , and discomfort . Six hundred women with bilaterally symmetrical starburst telangiectasias or varicose veins were entered into the study . Sodium chloride 11.7 % appeared to be the minimal sclerosant concentration of saline that produced the most effective vein sclerosis of vessels of less than 8 mm in diameter , while producing the least morbidity . The optimal concentration of the sclerosant may vary with the diameter of the vessels under therapeutic consideration 1 . The current practice of operating upon patients with varicose veins as the treatment of choice costs more than £ 15 millions a year Abstract Patients having their varicose veins injected normally wear compression b and ages for a period of up to 6 weeks , and various authors have stressed the success in injection therapy is closely related to this . On the basis of previous work ( T. B. Raj , G. S. , Makin , and M. Goddard , Brit . J. Surg . 67 , 122 ( 1980 ) ) showing that the pressure tends to fall significantly with time and at 8–10 hr it is nearly zero , a r and om trial on the use of compression b and ages in sclerotherapy was carried out . Patients ( 112 ) were divided into two groups and were allocated to wear b and ages for either 6 weeks or 8 hr . At 6 weeks , the result of the treatment was assessed by the injecting surgeon , the patient , and an independent surgeon who was unaware of the type of treatment . The results show that : (i)at 6 weeks there was no significant difference in the result between the two groups ; (ii)there was 71 % agreement between the injecting surgeon and the independent surgeon ; (iii)there was only 42 % agreement between the patient and the injecting surgeon , and 48 % between the patient and independent assessor ; (iv)the correlation between patient 's symptomatic improvement with cosmetic improvement was only 53 % The risk of thrombosis after lower-extremity sclerotherapy is still an unresolved issue . This study was conducted to investigate the influence of sclerotherapy on coagulation and fibrinolysis by examining 20 patients who underwent surgical procedures , 10 of whom were treated by surgery alone ( control group ) , while the other 10 were given sclerotherapy using 1 % hydroxypolyaetoxydodecan as polidocanol ( sclerotherapy group ) . Sex , age , and severity of disease was comparable between the two groups . No significant difference was found in the transient elevation of acute phase proteins , C-reactive protein ( CRP ) , or fibrinogen . Thrombin antithrombin III complex ( TAT ) , a marker of coagulation , transiently increased following treatment . In the control group , TAT peaked 3 days after treatment , whereas in the sclerotherapy group the elevation was prolonged , peaking 7 days after treatment . Elevation of the markers of fibrinolysis , plasmin plasmin inhibitor complex ( PIC ) and fibrin degradation products ( FDP ) , was slower than that of TAT , peaking 7 days after treatment in both groups , the plasma PIC being significantly enhanced 7 days after treatment in the sclerotherapy group . A significant decrease in the platelet count was observed 3 days after treatment in the sclerotherapy group . These results suggest that sclerotherapy may enhance coagulation or fibrinolysis after surgical procedures OBJECTIVES several studies have used duplex ultrasound to assess valvular incompetence in symptomatic patients . This cross-sectional survey was performed to determine , for the first time in a general population sample , the relationship between trunk varices and the presence of reflux in lower limb venous segments . MATERIAL S AND METHODS 1238 subjects ( 554 male , 684 female ) , aged 18 - 64 years , were r and omly selected . The presence and severity of any trunk varices was assessed and classified into Grade s 1 - 3 ; hyphenweb and reticular varices were noted . The presence or absence of reflux > or = 0.5 s in five deep and three superficial venous segments in each leg was assessed using duplex ultrasound . RESULTS the prevalence of reflux increased in both superficial and deep segments with more severe grade s of trunk varices ( p < or = 0.01 ) , except the upper SFV in women . Fifteen per cent of females showed reflux confined to the superficial system , compared with 9 % of males ( p < or = 0.001 ) ; 22 % of males showed deep reflux , compared with 11 % of females ( p < or = 0.001 ) . 71 % of men and 48 % of women with Grade 2 - 3 trunk varices had mixed deep and superficial reflux . Above-knee popliteal segments had a higher prevalence of reflux than lower SFV segments in all groups . There was no consistent relationship between the presence of hyphenweb or reticular varices and deep or superficial reflux . CONCLUSION segmental venous reflux can be detected in the deep and superficial leg veins of subjects without trunk varices , but superficial and mixed reflux are increasingly found in subjects with more severe varices |
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